selective IgM deficiency

Selective IgM deficiency (SIgMD) is a rare immune disorder that has been reported in association with serious infections, such as bacteria in the blood (bacteremia, also known as septicemia). Although SIgMD was first described in two children, the disorder can occur in babies, children, and adults. It is characterized by isolated absence or deficiency of immunoglobulin M (IgM), normal levels of other immunoglobulins, and recurrent infections (especially by Staphylococcus aureus, Streptococcus pneumoniae, Hemophilus influenza). The cause is still unclear. The diagnosis includes isolated deficiency ofIgM in the blood and no other immunodeficiency or secondary cause of low IgM. Patients with SIgMD and recurrent infections are managed like other antibody defects and deficiencies. It is suggested that people with SIgMD have pneumococcal and meningococcal vaccines, people with SIgMD who have recurrent infections should have prophylactic antibiotics and immune globulin replacement.


Bloom syndrome

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Bloom syndrome (BSyn) is a rare chromosomal breakage syndrome characterized by a marked genetic instability associated with pre- and postnatal growth retardation, facial sun-sensitive telangiectatic erythema, increased susceptibility to infections, and predisposition to cancer.


Congenital Disorder of Natural Immunity

A broad classification of inherited disorders presenting at birth that affect the initial immunologic response to infection. In these disorders, the primary role of innate immunity to detect and neutralize pathogens which the individual has not been previously exposed is decreased or ineffective.


PMM2-congenital disorder of glycosylation

The most frequent form of congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults.


Fanconi anemia complementation group E

Fanconi anemia caused by mutations of the FANCE gene. This is a protein coding gene. It is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2.


autosomal recessive multiple pterygium syndrome

A rare congenital disorder, this is the non-lethal variant of multiple pterygium syndrome, characterized by orthopedic and craniofacial abnormalities, pterygium and akinethesia. The majority of cases are autosomal dominant.


type 3 autoimmune lymphoproliferative syndrome

A rare, primary immunodeficiency. It is caused by a currently undetermined defect in the Fas-induced apoptosis pathway. No mutations in Fas, FASLG or CASP10 are detectable. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.


ALG3-congenital disorder of glycosylation

A form of congenital disorders of N-linked glycosylation characterized by severe neurological involvement, including hypotonia, developmental delay, intellectual disability, postnatal microcephaly, and progressive brain and cerebellar atrophy. Epilepsy with hypsarrythmia is frequently reported. Additional features that may be observed include failure to thrive, arthrogryposis multiplex congenita (AMC), vision impairment (optic atrophy, iris coloboma) and facial dysmorphism (hypertelorism with a broad nasal bridge, large and thick ears, thin lips, micrognathia). The disease is caused by loss of function mutations of the gene ALG3 (3q27.3).


Richter syndrome

Transformation of chronic lymphocytic leukemia into aggressive non-Hodgkin's lymphoma, usually diffuse large B-cell lymphoma (immunoblastic or centroblastic variant). Occasional cases of transformation to Hodgkin's lymphoma have also been described, particularly in patients treated with purine nucleotide analogs. Molecular genetic studies suggest that in approximately half of the cases, the lymphoma is clonally related to the underlying chronic lymphocytic leukemia, whereas in the remaining cases the lymphoma probably represents a secondary, unrelated neoplasm.


Melkersson-Rosenthal syndrome

The Melkersson-Rosenthal syndrome is a rare disorder characterized by a triad of recurrent orofacial swelling, relapsing facial paralysis and fissured tongue and onset in childhood or early adolescence. It has an estimated incidence of 8/10,000. The etiology is unknown but hereditary predisposition is suspected.


Multiple Endocrine Neoplasia Type 5

An inherited neoplastic syndrome caused by mutations in the MYC-associated factor X (MAX) gene. It is associated with the development of paragangliomas/pheochromocytomas, pituitary neuroendocrine tumors, and parathyroid adenomas. Renal cell carcinomas, squamous cell carcinomas, breast carcinomas, lung carcinomas, and endometrial carcinomas have also been reported.


myelodysplastic syndrome with multilineage dysplasia

Refractory cytopenias with multilineage dysplasia (RCMD) is a frequent subtype of myelodysplastic syndrome (MDS) characterized by 1 or more cytopenias in the peripheral blood and dysplasia in 2 or more myeloid lineages.


Hemophagocytic lymphohistiocytosis that is resistant to treatment.


Meigs syndrome

A rare syndrome affecting females. It is characterized by pleural effusion, ascites and non-malignant ovarian neoplasm. This syndrome usually follows a benign course. Prognosis is favorable following surgical resection of the ovarian mass.


familial cold autoinflammatory syndrome 2

An autoinflammatory disease caused by mutations in the NLRP12 gene. It is characterized by periodic fevers beginning in the first year of life that are triggered by cold exposure. Episodes occur more than once per month.


carcinoid syndrome

A syndrome characterized by signs and symptoms caused by advanced carcinoid tumors. They include skin flushing, diarrhea, wheezing, and tachycardia.


Perforin Deficiency

A condition of decreased or absent presence of perforin. Deficiency of this protein is associated with T-cell lymphoblastic lymphoma, aplastic anemia, hemophagocytic lymphohistiocytosis familial type 2, autoimmune lymphoproliferative syndrome and other lymphoproliferative disorders, including various forms of lymphoma.


Neonatal Drug Withdrawal

A constellation of neurobehavioral features observed following cessation or reduction of antenatal or postnatal drug exposure.


AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

An autosomal dominant condition caused by mutations(s) in the AHDC1 gene, encoding transcription factor Gibbin. It has a broad clinical spectrum, which includes impaired intellectual development, obstructive sleep apnea and mild facial dysmorphia.


familial episodic pain syndrome with predominantly lower limb involvement

A rare, autosomal dominant disorder caused by mutation in the SCN11A gene. It is characterized by intense episodic pain mainly affecting the distal lower extremities in early childhood. The pain diminishes with age.


autosomal recessive Kenny-Caffey syndrome

An autosomal recessive form of Kenny-Caffey syndrome due to mutation(s) in the TBCE gene, encoding tubulin-specific chaperone E. This condition is characterized by hypoparathyroidism with hypocalcemia, marked growth retardation, craniofacial anomalies, absent diploic space in the skull, cortical thickening of long bones with medullary stenosis, and small hands and feet.


Uveitis-glaucoma-hyphema syndrome

Clinical triad of uveitis, glaucoma, and hyphema (UGH), especially associated with the early anterior chamber intraocular lens (IOL). Glaucoma is believed to be caused by movement of the IOL against the iris causing release of inflammatory and red blood cell debris, which obstruct the trabecular meshwork. The haptic also may cause direct damage to the trabecular meshwork contributing to the glaucoma. Incidence of UGH is dependent on both surgical methodology applied in the cataract population and type of IOL used. UGH is particularly common if metal clip lenses have been used. Components of the condition may be reversed if the offending IOL is removed before permanent damage has occurred.


Cri-du-chat syndrome

Monosomy 5p, also known as Cri du chat syndrome, is a rare autosomal deletion syndrome characterized by a mewing cry (cri du chat) in infancy, multiple congenital anomalies, intellectual disability, microcephaly, and facial dysmorphism.


androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterized by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46,XY individual with absent or partial responsiveness to age-appropriate levels of androgens. It comprises two clinical subgroups: complete AIS (CAIS) and partial AIS (PAIS).


Myelodysplastic Syndrome with Excess Blasts and Fibrosis

Myelodysplastic syndrome with excess blasts associated with significant reticulin fibrosis of the bone marrow.


immunodeficiency 27A

A genetic condition caused by mutation(s) in the IFNGR1 gene, encoding interferon gamma receptor 1, resulting in impairment of interferon-gamma mediated immunity. Clinically, it is characterized by predisposition to illness caused by moderately virulent mycobacterial species.


CHARGE syndrome

CHARGE syndrome is a multiple congenital anomaly syndrome characterized by the variable combination of multiple anomalies, mainly Coloboma; Choanal atresia/stenosis; Cranial nerve dysfunction; Characteristic ear anomalies (known as the major 4 C's).


cardiospondylocarpofacial syndrome

Cardiospondylocarpofacial syndrome is characterized by mitral insufficiency, conductive deafness, short stature, and skeletal anomalies (bony fusion involving the cervical vertebrae, the ossicles, and the carpal and tarsal bones). It has been described in three members of one family. The mode of inheritance is likely to be autosomal dominant with incomplete penetrance.


Cornelia de Lange syndrome

A rare syndrome characterized by low birth weight, delayed growth, intellectual disabillity, behavioral problems, and a distinctive facial appearance (thin, arched eyebrows, low set ears, small teeth, and small nose). The majority of cases are caused by mutations in the NIPBL gene. Less severe forms of the syndrome are caused by mutations in the SMC1A and SMC3 genes.


ataxia-pancytopenia syndrome

A rare genetic disease characterized by cerebellar ataxia, cytopenias and predisposition to bone marrow failure and myeloid leukemia. Neurologic features variably include slowly progressive cerebellar ataxia or balance impairment with cerebellar atrophy and periventricular white matter T2 hyperintensities in brain MRI, horizontal and vertical nystagmus, dysmetria, dysarthria, pyramidal tract signs and reduced nerve conduction velocity. Hematological abnormalities are variable and may be intermittent and include cytopenias of all cell lineages, immunodeficiency, myelodysplasia and acute myeloid leukemia.


ring chromosome 21

Ring chromosome 21 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including growth retardation, developmental delay, intellectual disability, epilepsy, microcephaly, short stature, dysmorphic features, hypogammaglobulinemia, thrombocytopenia and unspecific skeletal anomalies (hemivertebrae, clinodactyly, syndactyly). In rare cases, it has been described in phenotypically normal individuals.


Acquired Hypogammaglobulinemia

A primary immunodeficiency characterized by low levels or absence of all the immunoglobulin classes and lack of B-lymphocytes or plasma cells. It results in recurrent bacterial infections. Complications include autoimmune phenomena and cancer development.


sterile multifocal osteomyelitis with periostitis and pustulosis

An autoinflammatory disease caused by mutations in the IL1RN gene, which encodes the IL1 receptor antagonist. It presents in infancy, and is characterized by systemic inflammation, pustular rash, bone pain, sterile osteitis, and periostitis.


congenital myasthenic syndrome 6

Congenital myasthenic syndrome caused by mutation(s) in the CHAT gene, encoding choline O-acetyltransferase. It is inherited in an autosomal recessive manner.


alpha thalassemia-X-linked intellectual disability syndrome

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal.


multiple endocrine neoplasia type 2B

Multiple endocrine neoplasia caused by mutation of the RET gene. Patients develop medullary thyroid carcinomas and numerous neural defects including neuromas.


2q37 microdeletion syndrome

A chromosomal anomaly involving deletion of chromosome band 2q37 and manifests as three major clinical findings: developmental delay, skeletal malformations and facial dysmorphism.


X-linked lymphoproliferative disease due to SH2D1A deficiency

A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked SH2D1A gene, resulting in B cell lymphoproliferation and manifesting with various phenotypes which include EBV-driven severe or fulminant mononucleosis, hemophagocytic lymphohistiocytosis (presenting with fulminant hepatitis, hepatic necrosis, bone marrow hypoplasia, and neurological involvement), hypogammaglobulinemia, and B-cell lymphoma. Additional variable manifestations include vasculitis, lymphomatoid granulomatosis, aplastic anemia, and chronic gastritis. Occasionally, T-cell lymphoma may be observed. Laboratory findings include normal or increased activated T cells and reduced memory B cells.


Hereditary Myelodysplastic Syndrome

Myelodysplastic syndrome caused by inherited damaging mutations in cancer susceptibility genes.


Robinow syndrome

Robinow syndrome (RS) is a rare genetic syndrome characterized by limb shortening and abnormalities of the head, face and external genitalia.


asphyxiating thoracic dystrophy 3

An asphyxiating thoracic dystrophy that has material basis in homozygous or compound heterozygous mutation in the DYNC2H1 gene on chromosome 11q22.


severe combined immunodeficiency due to DCLRE1C deficiency

Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation.


Wiskott-Aldrich syndrome 2

Any Wiskott-Aldrich syndrome in which the cause of the disease is a mutation in the WIPF1 gene.


Myelodysplastic Syndrome/Acute Myeloid Leukemia with Mutated TP53

Myelodysplastic syndrome/acute myeloid leukemia characterized by the presence of TP53 gene mutations. There are 10%-19% blasts in bone marrow or peripheral blood.


Cernunnos-XLF deficiency

Cernunnos-XLF deficiency is a rare form of combined immunodeficiency characterized by microcephaly, growth retardation, and T and B cell lymphopenia.


Mayer-Rokitansky-Kuster-Hauser syndrome

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome describes a spectrum of Mullerian duct anomalies characterized by congenital aplasia of the uterus and upper 2/3 of the vagina in otherwise phenotypically normal females. It can be classified as either MRKH syndrome type 1 (corresponding to isolated utero-vaginal aplasia) or MRKH syndrome type 2 (utero-vaginal aplasia associated with other malformations).


adult Fanconi syndrome

Probably related to a recessive gene, this is Fanconi Syndrome, characterized by adult onset.


Robertsonian translocation Down syndrome

Chromosomal disorder in which (part or full) chromosome 21 is attached to another chromosome, resulting in the presence of a third copy of part of full chromosome 21 genetic material. A Robertsonian translocation is a structural chromosomal anomaly in which two acrocentric chromosomes break, resulting in the fusion of the nonhomologous chromosomes’ long arms to form a single, large chromosome.


An autosomal recessive condition caused by mutation(s) in the STAMBP gene, encoding STAM-binding protein. It is characterized by severe microcephaly, diffuse cutaneous capillary malformations, refractory epilepsy, and developmental delay.


Primary Sjögren's syndrome

Sjogren syndrome without a concomitant systemic autoimmune disorder.


dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome

A syndrome is characterized by the association of dilated cardiomyopathy and hypergonadotropic hypogonadism (DCM-HH).


Lesch-Nyhan syndrome

Lesch-Nyhan syndrome (LNS) is the most severe form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, a hereditary disorder of purine metabolism, and is associated with uric acid overproduction (UAO), neurological troubles, and behavioral problems.


congenital T-cell immunodeficiency

A broad classification of inherited disorders presenting at birth that affect the cell-mediated aspect of the immune response. Circulating numbers of T lymphocytes are decreased or ineffective.


Ectopic growth hormone secretion

A syndrome characterized by abnormal secretion of growth hormone in conjunction with neoplastic growth occurring anywhere in the body.


Bohring-Opitz syndrome

Bohring-Opitz syndrome is characterized by intrauterine growth retardation (IUGR), failure to thrive, facial dysmorphism (prominent metopic suture and forehead nevus flammeus, a low frontal and temporal hairline with hirsutism, puffy cheeks, upslanting palpebral fissures, exophthalmos, hypertelorism, cleft lip and palate, retrognathia and low set ears), flexion deformities of the elbows and wrists, camptodactyly, ulnar deviation of the fingers, foot anomalies and severe developmental delay. Less than 20 patients have been described so far. Although the large majority of reported cases occurred sporadically, autosomal recessive inheritance has also been reported.


angioosteohypertrophic syndrome

A congenital vascular bone syndrome (CVBS) characterized by the presence of a vascular malformation in a limb, mainly of the arteriovenous type, which results in overgrowth of the affected limb.


Zellweger spectrum disorders

The most severe variant seen in the peroxisome biogenesis disorders that is characterized by neuronal migration defects in the brain, dysmorphic craniofacial features, profound hypotonia, neonatal seizures, and liver dysfunction.


ring chromosome 18

Ring chromosome 18 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including hypotonia, neonatal feeding and respiratory difficulties, microcephaly, global developmental delay and intellectual disability, growth hormone deficiency, hypothyroidism, hearing loss, aural atresia, dysmorphic facial features and behavioral characteristics.


long QT syndrome 5

Any long QT syndrome in which the cause of the disease is a mutation in the KCNE1 gene.


Susac syndrome

Susac syndrome (SS) is a rare disorder characterized by the triad of central nervous system (CNS) dysfunction, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss (SNHL). It is presumably due to autoimmune-mediated occlusions of microvessels in the CNS, the retina, and the inner ear.


Cockayne syndrome type 1

Cockayne syndrome caused by mutation(s) in the ERCC8 gene, encoding DNA excision repair protein ERCC-8.


Ehlers-Danlos syndrome, kyphoscoliotic type 1

A form of Ehlers-Danlos syndrome characterized by severe hypotonia and kyphoscoliosis at birth, generalized joint hyperextensibility and ocular globe fragility.


macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

An inherited giant platelet disorder with a complex phenotype characterized by congenital thrombocytopenia and possible subsequent manifestations of sensorineural hearing loss, presenile cataracts, elevation of liver enzymes, and/or progressive nephropathy often leading to end-stage renal disease (ESRD). Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly and Sebastian syndrome, previously described as distinct disorders, represent some of the different clinical presentations of MYH9-RD.


Diamond-Blackfan anemia 8

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS7 gene.


psoriasis 14, pustular

Any psoriasis in which the cause of the disease is a mutation in the IL36RN gene.


Severe Combined Immunodeficiency due to CD45 Deficiency

An autosomal recessive condition caused by mutation(s) in the PTPRC (CD45) gene, encoding receptor-type tyrosine-protein phosphatase C. It is characterized by severe combined immunodeficiency that is T-cell negative, B-cell positive, and NK cell positive.


primary Fanconi syndrome

A condition in which the kidneys do not absorb certain substances into the body. These substances, such as cysteine, fructose, galactose, or glycogen, are lost in the urine. Fanconi syndrome is thought to be caused by genetic and environmental factors, and it may be diagnosed at any age. Symptoms of Fanconi syndrome include increased urine production (which may cause dehydration), weakness, and abnormalities of the bones.


COVID-19-Associated Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


hyper-IgM syndrome

A primary immune deficiency disorder characterized by defective CD40 signaling; via B cells affecting class switch recombination (CSR) and somatic hypermutation.


gray platelet syndrome

Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear.


Jeune syndrome

Jeune syndrome, also called asphyxiating thoracic dystrophy, is a short-rib dysplasia characterized by a narrow thorax, short limbs and radiological skeletal abnormalities including "trident" aspect of the acetabula and metaphyseal changes.


Fanconi anemia complementation group O

Any Fanconi anemia in which the cause of the disease is a mutation in the RAD51C gene.


Poland syndrome

Poland syndrome is marked by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand anomalies, including symbrachydactyly.


Ectopic prolactin secretion

A syndrome characterized by abnormal secretion of prolactin in conjunction with neoplastic growth occurring anywhere in the body.


Myelodysplastic Syndrome with Biallelic TP53 Inactivation

Myelodysplastic syndrome characterized by the presence of biallelic TP53 inactivating alterations. They include biallelic TP53 gene mutations or one TP53 gene mutation and concurrent copy loss of TP53. There are less than 20% blasts in bone marrow and peripheral blood. It is associated with a poor prognosis.


schwannomatosis

Rare genetic disorder caused by mutations in the SMARCB1 and LZTR1 genes. It is characterized by the presence of multiple Schwannomas.


Saethre-Chotzen syndrome

Saethre-Chotzen syndrome (SCS) is an inherited craniosynostosis syndrome characterized by unilateral or bilateral coronal synostosis, facial asymmetry, ptosis, strabismus and small ears with prominent crus, among other less common manifestations.


Rett syndrome

A severe neurodevelopmental disorder affecting the central nervous system.


alcohol sensitivity, acute

Alcohol intolerance is characterized by immediate unpleasant reactions after drinking alcohol. The most common signs and symptoms of alcohol intolerance are stuffy nose and skin flushing. Alcohol intolerance is caused by a genetic condition in which the body is unable to break down alcohol efficiently, usually found in Asians. These individuals accumulate acetaldehyde, the primary metabolite of ethanol, because of a genetic polymorphism of aldehyde dehydrogenase (ALDH) that metabolizes acetaldehyde to nontoxic acetate. The only way to prevent alcohol intolerance reactions is to avoid alcohol. Alcohol intolerance isn't an allergy. However, in some cases, what seems to be alcohol intolerance may be a reaction to something in an alcoholic beverage, such as chemicals, grains or preservatives. Combining alcohol with certain medications also can cause reactions. In rare instances, an unpleasant reaction to alcohol can be a sign of a serious underlying health problem that requires diagnosis and treatment.


congenital myasthenic syndrome 12

Any congenital myasthenic syndromes with glycosylation defect in which the cause of the disease is a mutation in the GFPT1 gene.


macrophage activation syndrome

A complication of rheumatic disease that is caused by excessive activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages. It is characterized by fever, pancytopenia, liver insufficiency, coagulopathy and neurologic symptoms.


Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is a rare multisystemic syndrome characterized by chronic and usually mild neutropenia, pancreatic exocrine insufficiency associated with steatorrhea and growth failure, skeletal dysplasia with short stature, and an increased risk of bone marrow aplasia or leukemic transformation.


An autosomal recessive subtype of trichothiodystrophy caused by mutation(s) in the TARS1 gene, encoding threonine-tRNA ligase 1, cytoplasmic.


lymphedema-distichiasis syndrome

Lymphedema - distichiasis is a rare syndromic lymphedema disorder characterized by lower-limb lymphedema and varying degrees of abnormal growth of eyelashes from the orifices of the Meibomian glands (distichiasis), with occasional associated manifestations.


Diamond-Blackfan anemia 7

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL11 gene.


rapid-onset childhood obesity-hypothalamic dysfunction-hypoventilation-autonomic dysregulation syndrome

A very rare disorder that appears after the first year and a half of life in previously healthy children. It is characterized by rapid-onset weight gain, hypothalamic dysfunction, breathing abnormalities, and autonomic system dysregulation. The hypothalamic dysfunction manifestations include inability to maintain normal water balance, high prolactin levels, low thyroid, low cortisol, and early or late puberty. The breathing abnormalities include sleep apnea and alveolar hypoventilation, requiring ventilation support. The autonomic system dysregulation includes eye abnormalities, intestinal abnormalities, temperature dysregulation, and low heart rhythm. This disorder requires early recognition because it may lead to cardiorespiratory arrest. Up to 40% of the patients develop tumors of neural crest origin.


schwannomatosis 2

Schwannomatosis caused by germline mutations in the LZTR1 gene.


Kleine-Levin syndrome

Kleine-Levin syndrome (KLS) is a rare neurological disorder of unknown origin characterized by relapsing-remitting episodes of hypersomnia in association with cognitive and behavioral disturbances.


distal monosomy 10p

Distal monosomy 10p is a rare chromosomal disorder in which the tip of the short arm (p arm) of chromosome 10 is deleted resulting in a variable phenotype depending on the size of the deletion. The deletion may involve only the terminal 10p15 band, or extend towards the centromere to bands 10p14 or 10p13.


Marshall syndrome

Marshall syndrome is a malformation syndrome that is characterized by facial dysmorphism, severe hypoplasia of the nasal bones and frontal sinuses, ocular involvement, early-onset hearing loss, skeletal and anhidrotic ectodermal anomalies and short stature with spondyloepiphyseal dysplasia and early-onset osteoarthritis.


pentasomy X

Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX).


Complete Trisomy 21 Syndrome

A syndrome characterized by the presence of three complete copies of genetic material for chromosome 21, instead of the normal two. It leads to a variety of abnormalities that include mental retardation, macroglossia, microgenia, epicanthic eyelids, and a single transverse palmar crease.


autosomal recessive hypohidrotic ectodermal dysplasia

A rare autosomal recessive disorder characterized by developmental abnormalities of the skin, sweat glands, hair and nails. Patients have a reduced ability to sweat. Other signs and symptoms include hypotrichosis and teeth malformations.


15q11q13 microduplication syndrome

The 15q11-q13 microduplication (dup15q11-q13) syndrome is characterized by neurobehavioral disorders, hypotonia, cognitive deficit, language delay and seizures. Prevalence is unknown.


proximal 16p11.2 microdeletion syndrome

A chromosomal anomaly characterized by developmental and language delays, mild intellectual disability, social impairments (autism spectrum disorders), mild variable dysmorphism and predisposition to obesity.


ALG6-congenital disorder of glycosylation 1C

A form of congenital disorders of N-linked glycosylation characterized by feeding problems, mild-to-moderate neurologic involvement with hypotonia, poor head control, developmental delay, ataxia, strabismus, and seizures, ranging from febrile convulsions to epilepsy. Retinal degeneration has also been reported. A minority of patients show other manifestations, particularly intestinal (such as protein-losing enteropathy) and liver involvement. The disease is caused by loss of function mutations of the gene ALG6 (1p31.3).


Allan-Herndon-Dudley syndrome

A syndrome with neuromuscular involvement characterized by infantile hypotonia, muscular hypoplasia, spastic paraparesis with dystonic/athetoic movements, and severe cognitive deficiency.


Jacobsen syndrome

A multiple congenital anomaly/intellectual disability contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11.


Postural Orthostatic Tachycardia Syndrome Associated with Post-Acute Sequelae of SARS-CoV-2 Infection

Postural orthostatic tachycardia syndrome (POTS) that started during probable or confirmed acute COVID-19 and persisted at least three months after the initial diagnosis of COVID-19.


trichorhinophalangeal syndrome type I

An autosomal dominant malformation syndrome caused by mutations in TRPS1 characterized by distinctive craniofacial and skeletal abnormalities. TRPS I patients have sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature.


Waterhouse-Friderichsen syndrome

A serious disorder characterized by massive adrenal gland hemorrhage secondary to a bacterial infection, most often Neisseria meningitidis infection. It is manifested with decreased blood pressure, shock, disseminated intravascular coagulation, and adrenocortical insufficiency.


paraneoplastic limbic encephalitis

A rare disorder characterized by degenerative changes in the limbic area of the brain. Causes include infections and autoimmune conditions; it may also manifest as a paraneoplastic syndrome, most often caused by small cell lung carcinoma. Signs and symptoms include behavioral changes, hallucinations and dementia.


Barre-Lieou syndrome

A neurologic syndrome following injury of the spinal sympathetic nerves of the neck. The injury usually results from arthritis or pinching by the adjacent vertebrae. Symptoms include facial pain, chronic allergies, dizziness, neck pain, ear pain and vertigo.


Fanconi anemia complementation group F

Fanconi anemia caused by mutations of the FANCF gene. This gene encodes a polypeptide with homology to the prokaryotic RNA-binding protein ROM.


Ellis-van Creveld syndrome

Ellis-van Creveld syndrome (EVC) is a skeletal and ectoderlam dysplasia characterized by a tetrad of short stature, postaxial polydactyly, ectodermal dysplasia, and congenital heart defects.


Alice in Wonderland syndrome

A disorienting neuropsychological condition that affects perception. People experience size distortion such as micropsia, macropsia, pelopsia, or teleopsia. Size distortion may occur of other sensory modalities.


complete androgen insensitivity syndrome

Complete androgen insensitivity syndrome (CAIS) is a form of androgen insensitivity syndrome (AIS), a disorder of sex development (DSD), characterized by the presence of female external genitalia in a 46,XY individual with normal testis development but undescended testes and unresponsiveness to age-appropriate levels of androgens.


Refractory Myelodysplastic Syndrome

Myelodysplastic syndrome that does not respond to treatment.


Diamond-Blackfan anemia 1

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS19 gene.


CREST syndrome

CREST syndrome is a subtype of limited cutaneous systemic sclerosis (lcSSc) whose name is an acronym for the cardinal clinical features of the syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia.


Neurofibromatosis Type 1 with Inoperable, Progressive, Symptomatic Plexiform Neurofibromas

Progressive, symptomatic neurofibromatosis type 1 associated with plexiform neurofibromas that cannot be removed surgically without risk of substantial morbidity.


Neoplastic Syndromes, Hereditary

An inherited genetic condition in which members within a family are at an increased risk for the development of benign and/or malignant neoplasms.


Aicardi syndrome

Aicardi syndrome is a rare neurodevelopmental disorder defined by the triad of agenesis of the corpus callosum (total or partial), typical chorioretinal lacunae and infantile spasms that affect almost exclusively females.


selective IgD deficiency disease

A rare dysgammaglobulinemia characterized by low or undetectable serum levels of immunoglobulin class D (IgD). It is an uncommon primary antibody deficiency. It is most likely an inherited immunodeficiency. It may be caused by decreased or inefficient production of IgD from progenitor B cells without any corresponding decreases in the other isotypes. Most affected persons are asymptomatic and do not appear to be at increased risk for infection.


Neutrophil Actin Defect

A genetic disorder characterized by defective polymorphonuclear cell actin function, resulting in impaired granulocyte motility.


Leaky Severe Combined Immunodeficiency

A form of severe combined immunodeficiency (SCID) that presents with T-cell counts that are higher than typical for SCID, and variable signs and symptoms including: itchy, erythematous skin, alopecia, hepatosplenomegaly, lymphadenopathy, anemia, thyroid dysfunction and diarrhea. T-cell counts may initially be noted to be within normal ranges since some may "leak" through into the peripheral blood affecting proper measurement.


multiple congenital anomalies-hypotonia-seizures syndrome 1

Any multiple congenital anomalies/dysmorphic syndrome-intellectual disability in which the cause of the disease is a mutation in the PIGN gene.


48,XXYY syndrome

The 48,XXYY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of an extra X and Y chromosome in males.


Hermansky-Pudlak syndrome 6

Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS6 gene.


acute motor and sensory axonal neuropathy

Acute motor-sensory axonal neuropathy (AMSAN) is a motor-sensory, axonal form of Guillain-Barre syndrome (GBS).


A hypereosinophilic syndrome characterized by the presence of a clonal T-cell population. Patients present with cutaneous findings including eczematous dermatitis, nodules, papules, and pruritis, rheumatological symptoms, gastrointestinal symptoms, and lymphadenopathy. Lymph node biopsies show eosinophilia, atypical lymphocytes, clonally rearranged T-cells, and architectural distortion. Skin biopsies may also show the clonally rearranged T-cell population.


bone marrow failure syndrome

A familial or acquired bone marrow failure syndrome.


Acroosteolysis dominant type

A rare genetic osteolysis syndrome characterized by acroosteolysis of distal phalanges and generalized osteoporosis, associated with additional ossification anomalies, craniofacial dysmorphism, dental anomalies and a wide range of other characteristics.


congenital disorder of glycosylation type 1E

The CDG (Congenital Disorders of Glycosylation) syndromes are a group of autosomal recessive disorders affecting glycoprotein synthesis. CDG syndrome type Ie is characterized by psychomotor delay, seizures, hypotonia, facial dysmorphism and microcephaly. Ocular anomalies are also very common.


congenital varicella syndrome

Fetal varicella syndrome (CVS) is an acquired developmental anomaly syndrome characterized by skin, neurological, ocular, limbs and growth defects secondary to maternal Varicella-Zoster Virus (VZV) infection.


Marfan syndrome

A disorder of the connective tissue. Connective tissue provides strength and flexibility to structures throughout the body such as bones, ligaments, muscles, walls of blood vessels, and heart valves. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). It is caused by mutations in the FBN1 gene, which provides instructions for making a protein called fibrillin-1. Marfan syndrome is inherited in an autosomal dominant pattern. At least 25% of cases are due to a new (de novo) mutation. Treatment is based on the signs and symptoms in each person.


Achenbach syndrome

A rare disorder which affects the volar surfaces of fingers. Clinical signs include recurrent, spontaneous or post-traumatic bruising of fingers. The clinical course of the resultant hematoma usually follows a pattern of resolution within days.


Severe Combined Immunodeficiency due to RAG2 Deficiency

An autosomal recessive condition caused by mutation(s) in the RAG2 gene, encoding V(D)J recombination-activating protein 2. It is characterized by severe combined immunodeficiency that is both T-cell and B-cell negative.


trichothiodystrophy 1, photosensitive

An autosomal recessive subtype of trichothiodystrophy caused by mutation(s) in the ERCC2 gene, encoding general transcription and DNA repair factor IIH helicase subunit XPD.


Hypocellular Myelodysplastic Syndrome

Myelodysplastic syndrome characterized by decreased cellularity in the bone marrow.


Myelodysplastic Syndrome/Acute Myeloid Leukemia with Myelodysplasia-Related Cytogenetic Abnormalities

Myelodysplastic syndromes/acute myeloid leukemias classified based on specific karyotype findings.


Fanconi anemia complementation group J

Fanconi anemia caused by mutations in the BRIP1 gene, encoding Fanconi anemia group J protein.


tetrasomy 12p

Pallister-Killian syndrome (PKS) is a rare multiple congenital anomaly/intellectual deficit syndrome caused by mosaic tissue-limited tetrasomy for chromosome 12p.


early-onset parkinsonism-intellectual disability syndrome

A basal ganglia disorder characterized by Parkinsonian-type symptoms (postural changes, tremor, rigidity), megalencephaly and variable intellectual deficit. Other signs are frontal bossing, persistent frontal lobe reflexes, strabismus and seizures. It has been described in three generations of one family. Transmission is X-linked, and the gene is located on chromosomal region Xq27.3-qter.


Congenital iodine deficiency syndrome of neurological type

Congenital iodine deficiency syndrome associated with mental retardation, deaf-mutism, and abnormal gait. It results from severe maternal iodine deficiency and hypothyroidism during pregnancy.


Wiskott-Aldrich syndrome

A rare, X-linked immunodeficiency syndrome characterized by eczema, thrombocytopenia, and recurrent pyogenic infection. It is seen exclusively in young boys. Typically, IgM levels are low and IgA and IgE levels are elevated. Lymphoreticular malignancies are common.


Fanconi anemia

Fanconi anemia (FA) is a hereditary DNA repair disorder characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors.


Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS) is a very rare genetic disease, characterized by permanent neonatal diabetes mellitus (PNDM) with multiple epiphyseal dysplasia and other clinical manifestations, including recurrent episodes of acute liver failure.


lethal multiple pterygium syndrome

Multiple pterygium syndrome lethal type is a very rare genetic condition affecting the skin, muscles and skeleton. It is characterized by minor facial abnormalities, prenatal growth deficiency, spine defects, joint contractures, and webbing (pterygia)of the neck, elbows, back of the knees, armpits, and fingers. Fetuses with this condition are usually not born. Some of the prenatal complications include cystic hygroma, hydrops, diaphragmatic hernia, polyhydramnios, underdevelopment of the heart and lungs, microcephaly, bone fusions, joint dislocations, spinal fusion, andbone fractures. Both X-linked and autosomal recessive inheritance have been proposed. Mutations in the CHRNG, CHRNA1, and CHRND genes have been found to cause this condition.


Bartter syndrome

Bartter syndrome is a group of rare renal tubular disease characterized by impaired salt reabsorption in the thick ascending limb of Henle's loop and clinically by the association of hypokalemic alkalosis, hypercalciuria/nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II.


severe combined immunodeficiency due to LCK deficiency

An extremely rare autosomal recessive condition caused by mutation(s) in the LCK gene, encoding tyrosine-protein kinase Lck. It is characterized by T-cell dysfunction.


A rare immunodeficiency syndrome characterized by the decrease of the CD4-positive lymphocytes below 300 per cubic millimeter in the absence of identifiable immunodeficiency causes. Patients with this syndrome are at an increased risk of opportunistic infections.


thrombocytopenia-absent radius syndrome

Thrombocytopenia-absent radius (TAR) syndrome is a very rare congenital malformation syndrome characterized by bilateral radial aplasia and thrombocytopenia.


otopalatodigital syndrome type 1

The mildest form of otopalatodigital syndrome spectrum disorder that is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.


Christianson syndrome

A very rare form of syndromic intellectual deficit characterized by microcephaly, severe developmental delay or regression, hypotonia, abnormal movements, and early-onset seizures.


Peters plus syndrome

An autosomal recessively inherited syndromic developmental defect of the eye characterized by a variable phenotype including Peters anomaly and other anterior chamber eye anomalies, short limbs, limb abnormalities (i.e. rhizomelia and brachydactyly), characteristic facial features (upper lip with cupid bow, short palpebral fissures), cleft lip/palate, and mild to severe developmental delay/intellectual disability. Other associated abnormalities reported in some patients include congenital heart defects (i.e. hypoplastic left heart, absence of right pulmonary vein, bicuspid pulmonary valve), genitourinary anomalies (hydronephrosis, renal hypoplasia, renal and ureteral duplication, multicystic dysplastic kidneys, glomerulocystic kidneys) and congenital hypothyroidism.


immunodeficiency 23

A condition of decreased or absent presence or activity of phosphoglucomutase 3. Deficiency of this protein is associated with immunodeficiency 23.


Perinatal Drug Withdrawal

Withdrawal signs and symptoms that present during the perinatal period and are caused by drug use by the pregnant mother.


T-B+ severe combined immunodeficiency due to gamma chain deficiency

Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.


Juvenile Primary Fibromyalgia Syndrome

Chronic, diffuse, non-inflammatory musculoskeletal pain disorder associated with fatigue and sleep disturbance that can occur in childhood and adolescence. Tender points are not necessary to make the diagnosis, but if present may be less numerous than found in adults.


Perinatal Blood Aspiration Syndrome

Respiratory distress in the newborn due to inhalation of blood; this is an unusual event and is sometimes linked to the non passage of meconium before delivery or mothers with antepartum hemorrhage.


short-rib thoracic dysplasia 6 with or without polydactyly

A group of rare, autosomal recessive inherited disorders characterized by a constricted thoracic cage, short ribs, and a 'trident' appearance of the acetabular roof. Polydactyly may or may not be present. Other abnormalities include cleft lip and palate and abnormalities of the brain, eye, heart, liver, pancreas, intestine, kidney, and genitalia.


long QT syndrome 3

An autosomal dominant condition caused by mutation(s) in the SCN5A gene, encoding sodium channel protein type 5 subunit alpha. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death.


mucopolysaccharidosis type 4B

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme beta galactosidase. It is characterized by skeletal dysplasia and short stature.


trichothiodystrophy 2, photosensitive

An autosomal recessive subtype of trichothiodystrophy caused by mutation(s) in the ERCC3 gene, encoding general transcription and DNA repair factor IIH helicase subunit XPB.


Dyggve-Melchior-Clausen disease

Dyggve-Melchior-Clausen disease (DMC) is a rare skeletal disorder belonging to the group of spondyloepimetaphyseal dysplasias.


Fanconi anemia complementation group G

Fanconi anemia caused by mutations of the FANCG gene.


Carpenter syndrome

An extremely rare autosomal recessive syndrome characterized by premature closure of cranial sutures leading to cone-shaped head, fusion of the digits, and the presence of more digits than normal. It may be associated with heart defects, single horseshoe-shaped kidney, short stature, undescended testes, and mild mental retardation.


Ehlers-Danlos syndrome, vascular type

Ehlers-Danlos syndrome type IV, also known as the vascular type of Ehlers-Danlos syndrome (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS.


Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant and premature aging disease, beginning in childhood and characterized by growth reduction, failure to thrive, a typical facial appearance (prominent forehead, protuberant eyes, thin nose with a beaked tip, thin lips, micrognathia and protruding ears) and distinct dermatologic features (generalized alopecia, aged-looking skin, sclerotic and dimpled skin over the abdomen and extremities, prominent cutaneous vasculature, dyspigmentation, nail hypoplasia and loss of subcutaneous fat).


combined immunodeficiency due to ZAP70 deficiency

Combined immunodeficiency due to ZAP70 deficiency is a very rare, severe, genetic, combined immunodeficiency disorder characterized by lymphocytosis, decreased peripheral CD8+ T-cells, and presence of normal circulating CD4+ T-cells, leading to immune dysfunction.


mucopolysaccharidosis type 3C

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme acetyl-CoA:alpha-glucosaminide acetyltransferase. It is characterized by behavioral changes, sleep disturbances, and mental developmental delays.


Takayasu arteritis

A rare inflammatory large-vessel vasculitis primarily affecting the aorta and its major branches, but also other large vessels, causing stenosis, occlusion, or aneurysm.


Recurrent Myelodysplastic Syndrome

The reemergence of myelodysplastic syndrome after a period of remission.


severe combined immunodeficiency due to DNA-PKcs deficiency

Severe combined immunodeficiency (SCID) due to DNA-PKcs deficiency is an extremely rare type of SCID characterized by the classical signs of SCID (severe and recurrent infections, diarrhea, failure to thrive), absence of T and B lymphocytes, and cell sensitivity to ionizing radiation.


synpolydactyly type 1

Any non-syndromic synpolydactyly in which the cause of the disease is a mutation in the HOXD13 gene.


UV-sensitive syndrome 2

Any UV-sensitive syndrome in which the cause of the disease is a mutation in the ERCC8 gene.


split hand-foot malformation 5

Split-hand/foot malformation mapped to chromosome 2q31.


Contrasexual Sexual Development

The development of secondary sexual characteristics contrary to pre-pubertal phenotype (feminization in boys; virilization in girls).


Secondary Myelodysplastic Syndrome

A myelodysplastic syndrome resulting from chemotherapy or radiation therapy for cancer or exposure to certain chemicals.


COFS syndrome

Cerebrooculofacioskeletal (COFS) syndrome is a rare genetic disorder, belonging to a family of diseases of DNA repair, characterized by a severe sensorineural involvement.


Hurler-Scheie syndrome

Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 (MPS1) between the two extremes Hurler syndrome and Scheie syndrome ; it is a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.


Secondary Sjögren's syndrome

Sjogren syndrome that occurs with another systemic autoimmune disorder, such as systemic lupus erythematosus or rheumatoid arthritis.


T-cell immunodeficiency

A broad classification of disorders that affect the cell-mediated aspect of the immune response. Circulating numbers of T lymphocytes are decreased or ineffective.


Diarrhea-associated hemolytic uremic syndrome

Hemolytic uremic syndrome caused by gastrointestinal infection, usually with shiga toxin-producing enterobacteria.


immunodeficiency 14

An autosomal dominant condition caused by mutation(s) caused by mutation(s) in the PIK3CD gene, encoding phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform. It is characterized by defects in T-cells and B-cells and recurrent sinopulmonary infections in childhood.


Gabriele de Vries syndrome

An autosomal dominant condition caused by mutation(s) in the YY1 gene, encoding transcriptional repressor protein YY1. It is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, and variable functional and morphological abnormalities.


hypohidrotic ectodermal dysplasia

A genetic disorder of ectoderm development characterized by malformation of ectodermal structures such as skin, hair, teeth and sweat glands. It comprises three clinically almost indistinguishable subtypes with impaired sweating as the key symptom: Christ-Siemens-Touraine (CST) syndrome (X-linked), autosomal recessive (AR), and autosomal dominant (AD) HED, as well as a fourth rare subtype with immunodeficiency as the key symptom (HED with immunodeficiency).


Jervell and Lange-Nielsen syndrome

An autosomal recessive inherited syndrome caused by mutations in the KCNE1 and KCNQ1 genes. It is characterized by congenital hearing loss and arrhythmia. It is a form of long QT syndrome.


Oncogenic osteomalacia

Oncogenic osteomalacia is characterized by the development of a tumor that causes the bones to be weakened. This occurs when a tumor secretes a substance called fibroblast growth factor 23 (FGF23). FGF23 inhibits the ability of the kidneys to absorb phosphate. Phosphate is important for keeping bones strong and healthy. Therefore, this disease is characterized by a softening and weakening of the bones (osteomalacia). The disease also results in multiple biochemical abnormalities including high levels of phosphate in the urine (hyperphosphaturia) and low levels of phosphate in the blood (hypophosphatemia). The majority of tumors that cause oncogenic osteomalacia are small and slow-growing. These tumors most commonly occur in the skin, muscles, or bones of the extremities or in the paranasal sinuses around the head. Most of these tumors are benign, meaning they are not associated with cancer. The exact reason that the tumors associated with oncogenic osteomalacia develop is not known. The disease is diagnosed when a person experiences clinical features such as bone weakening and hyperphosphaturia and a tumor is found by imaging of the body. Treatment of the disease consists of surgical removal of the tumor. The symptoms of the disease, including the weakening of the bones, typically resolve once the tumor is removed.


infantile-onset periodic fever-panniculitis-dermatosis syndrome

An autosomal recessive condition caused by mutation(s) in the OTULIN gene, encoding ubiquitin thioesterase otulin. It is characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy.


triploidy

Triploidy is a chromosome abnormality that occurs when there is an extra set of chromosomes present in each cell. Most pregnancies affected by triploidy are lost through early miscarriage. However, reports exist of some affected babies living up to five months. Those that survive are often mosaic. The signs and symptoms associated with triploidy vary but may include a variety of birth defects and an unusually small size. This condition does not run in families and is not associated with maternal or paternal age. Treatment is based on the signs and symptoms present in each person.


Opiate Withdrawal Syndrome

A syndrome that is defined by signs and symptoms related to abrupt or gradual stoppage of opioids use. They include strong cravings, sweating, nausea, vomiting, irritation, anxiety, muscle pain, dilated pupils and insomnia.


ectodermal dysplasia and immunodeficiency 2

A rare disorder caused by mutations in the NFKBIA gene resulting in an autosomal dominant inheritance pattern. It is characterized by abnormal development of ectodermal tissues including the skin, hair, teeth, and sweat glands and immune system deficiency. It results in dry and wrinkled skin, sparse scalp and body hair, missing teeth, and reduced ability to sweat. Patients have abnormally low levels of antibodies causing inability to fight infections.


vitamin K-antagonist embryofetopathy

A teratogenic disorder observed in a newborn or child of a mother who was exposed to warfarin during pregnancy. Manifestations include nasal bridge depression, nasal bones hypoplasia, microcephaly, congenital heart disorders, and brachydactyly.


Xq25 microduplication syndrome

An X-linked genetic condition caused by duplication of a small segment of Xq25, which may encompass the GRIA3 and STAG2 genes, encoding glutamate receptor 3 and cohesin subunit SA-2. It is characterized by intellectual disability and distinctive facial dysmorphisms.


leukocyte adhesion deficiency

Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency characterized by defects in the leukocyte adhesion process, marked leukocytosis and recurrent infections.


Rubinstein-Taybi syndrome

A rare malformation syndrome characterized by congenital anomalies (microcephaly, specific facial characteristics, broad thumbs and halluces and postnatal growth retardation), short stature, intellectual disability and behavioral characteristics.


Childhood Myelodysplastic Syndrome with Excess Blasts

Myelodysplastic syndrome with excess blasts that occurs during childhood.


Diamond-Blackfan anemia 10

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS26 gene.


granulomatous disease, chronic, X-linked

An X-linked recessive form of chronic granulomatous disease caused by mutation(s) in the CYBB gene, encoding cytochrome b-245 beta chain.


chromosome 10q23 deletion syndrome

10q22.3q23.3 microdeletion syndrome is a rare partial autosomal monosomy characterized by a mild facial dysmorphism variably including macrocephaly, broad forehead, hypertelorism or hypotelorism, deep-set eyes, upslanting or downslanting palpebral fissures, low-set ears, flat nasal bridge, smooth philtrum, thin upper lip), cleft palate, cerebellar and cardiac malformations, psychomotor development delay, and behavioral abnormalities (attention deficit hyperactivity disorder, autism). Other rare features may include congenital breast aplasia, arachnodactyly, joint hyperlaxity, club feet, feeding difficulties, failure to thrive.


IMAGe syndrome

IMAGe syndrome is characterized by the association of intrauterine growth retardation, metaphyseal dysplasia (and short limbs), adrenal hypoplasia congenita, and genital anomalies. It has been described in less than 20 cases. The patients also present with dysmorphic features (frontal bossing, broad nasal bridge, low-set ears). In boys, genital anomalies include bilateral cryptorchidism, hypospadias, micropenis, and hypogonadotropic hypogonadism. This syndrome is likely to be transmitted as an autosomal recessive trait.


Rabson-Mendenhall syndrome

Rabson-Mendenhall syndrome belongs to the group of extreme insulin-resistance syndromes (which also includes leprechaunism, the lipodystrophies, and the type A and B insulin resistance syndromes).


mulibrey nanism

A prenatal onset growth disorder with multiorgan manifestations.


49,XXXXY syndrome

The 49,XXXXY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of three extra X chromosomes in males.


partial androgen insensitivity syndrome

Partial androgen insensitivity syndrome (PAIS) is a disorder of sex development (DSD) distinct from complete AIS (CAIS) characterized by the presence of abnormal genital development in a 46,XY individual with normal testis development and partial responsiveness to age-appropriate levels of androgens.


Joubert syndrome 9

Any Joubert syndrome in which the cause of the disease is a mutation in the CC2D2A gene.


HELLP syndrome

A life-threatening condition that can potentially complicate pregnancy. It is named for 3 features of the condition: H emolysis, E levated L iver enzyme levels, and L ow P latelet levels. It typically occurs in the last 3 months of pregnancy (the third trimester) but can also start soon after delivery. A wide range of non-specific symptoms may be present in women with HELLP syndrome. Symptoms may include fatigue; malaise; fluid retention and excess weight gain; headache; nausea and vomiting; pain in the upper right or middle of the abdomen; blurry vision; and rarely, nosebleed or seizures. The cause of HELLP syndrome is not known, but certain risk factors have been associated with the condition. It is most common in women with preeclampsia or eclampsia. If not diagnosed and treated quickly, HELLP syndrome can lead to serious complications for the mother and baby.The main treatment is to deliver the baby as soon as possible, even if premature. Treatment may also include medications needed for the mother or baby, and blood transfusion for severe bleeding problems.


schwannomatosis 1

Schwannomatosis caused by germline mutations in the SMARCB1 gene.


multiple endocrine neoplasia

An autosomal dominant inherited neoplastic syndrome characterized by the development of various endocrine neoplasms and abnormalities in various anatomic sites. There are four types recognized: type 1 (MEN 1), caused by inactivation of the tumor suppressor gene MEN-1, type 2A (MEN 2A), caused by mutation of the RET gene, type 2B (MEN 2B) also caused by mutation of the RET gene, and type 4 (MEN 4) caused by mutation of the CDKN1B gene. Patients with MEN 1 may develop hyperparathyroidism and parathyroid gland adenomas, pituitary gland adenomas, pancreatic islet cell neoplasms, and carcinoid tumors. Patients with MEN 2A develop medullary thyroid carcinomas and may also develop pheochromocytomas and parathyroid gland hyperplasia. Patients with MEN 2B develop medullary thyroid carcinomas and numerous neural defects including neuromas. Patients with MEN 4 develop endocrine neoplasms, particularly in the parathyroid glands, pituitary, and pancreas.


SERKAL syndrome

SERKAL (SEx Reversion, Kidneys, Adrenal and Lung dysgenesis) syndrome is characterized by female to male sex reversal and developmental anomalies of the kidneys, adrenal glands and lungs.


Shprintzen-Goldberg syndrome

Shprintzen-Goldberg syndrome (SGS) is a very rare genetic disorder characterized by craniosynostosis, craniofacial and skeletal abnormalities, marfanoid habitus, cardiac anomalies, neurological abnormalities, and intellectual disability.


short rib-polydactyly syndrome

Short rib-polydactyly syndromes are a group of bone malformations characterized by a narrow thorax and polydactyly (usually preaxial).


cleft lip/palate-ectodermal dysplasia syndrome

An ectodermal dysplasia syndrome characterized by hair, skin and teeth anomalies, facial dysmophism with cleft lip and palate, cutaneous syndactyly and, in some cases, intellectual disability.


Weill-Marchesani syndrome

Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of the lens, severe myopia, and glaucoma.


VACTERL/vater association

VACTERL/VATER is an association of congenital malformations typically characterized by the presence of at least three of the following: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities.


UNC13D Deficiency

A condition of decreased or absent presence of protein unc-13 homolog D. Deficiency of this protein is associated with familial hemophagocytic lymphohistiocytosis 3.


selective immunoglobulin deficiency disease

A broad classification of dysgammaglobulinemias characterized by low or undetectable serum levels of one of the five immunoglobulin classes. Deficiencies of immunoglobulins present variably according to isotype. Selective deficiencies may be caused by decreased or inefficient production from progenitor B cells without any corresponding decreases in the other isotypes. The clinical course and prognosis is dependent upon the severity of the selective deficiency and associated morbidity.


Mobius syndrome

Moebius syndrome is a very rare congenital cranial dysinnervation disorder characterized by complete or incomplete facial paralysis in association with bilateral palsy of the abducens nerve causing impairment of ocular abduction. The syndrome also includes various other congenital anomalies.


SUNCT syndrome

SUNCT syndrome (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing) is a primary headache disorder characterized by unilateral trigeminal pain that occurs in association with ipsilateral cranial autonomic symptoms (conjunctival injection and tearing).


Fanconi anemia complementation group A

Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway.


atypical hemolytic-uremic syndrome

A rare, genetic thrombotic microangiopathy due to dysregulation of the alternative complement pathway and characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal dysfunction.


cerebrooculofacioskeletal syndrome 1

Any COFS syndrome in which the cause of the disease is a mutation in the ERCC6 gene.


Omenn syndrome

An inflammatory condition characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency (SCID).


Senior-Loken syndrome

Senior-Loken syndrome (SLSN) is a very rare autosomal recessive oculo-renal disease characterized by the association of nephronophthisis (NPHP), a chronic kidney disease, with retinal dystrophy.


paraneoplastic cerebellar degeneration

A rare, immune-mediated disorder characterized by cerebellar degeneration due to the presence of an often undetected malignancy (usually carcinoma or lymphoma) in an anatomic site other than the cerebellum. Signs and symptoms include progressive ataxia, dysarthria, and nystagmus.


encephalopathy due to GLUT1 deficiency

Glucose transporter type 1 (GLUT1) deficiency syndrome is characterized by an encephalopathy marked by childhood epilepsy that is refractory to treatment, deceleration of cranial growth leading to microcephaly, psychomotor retardation, spasticity, ataxia, dysarthria and other paroxysmal neurological phenomena often occurring before meals. Symptoms appear between the age of 1 and 4 months, following a normal birth and gestation.


progressive supranuclear palsy

A rare late-onset neurodegenerative disease characterized by supranuclear gaze palsy, postural instability, progressive rigidity, and mild dementia.


myelodysplastic syndrome with excess blasts-2

A myelodysplastic syndrome defined by 10-19% blasts in the bone marrow or 5-19% blasts in the blood and <10% blasts in the bone marrow. Approximately 33% of cases progress to acute leukemia. The prognosis is usually poor. (WHO)


Myoclonic-atonic epilepsy caused by mutation(s) in the SLC6A1 gene, encoding sodium- and chloride-dependent GABA transporter 1.


Diamond-Blackfan anemia 6

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL5 gene.


Severe Combined Immunodeficiency with Absence of T, Normal B Cells

An inherited, severe immunodeficiency disorder characterized by abnormalities in the development and function of T cell immunity. The peripheral T lymphocytes are absent or in very low counts. The B lymphocyte counts are normal.


ornithine translocase deficiency

A rare, genetic disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or coagulation defects or other chronic liver dysfunction.


Dubin-Johnson syndrome

Dubin-Johnson syndrome (DJS) is a benign, inherited liver disorder characterized clinically by chronic, predominantly conjugated, hyperbilirubinemia and histopathologically by black-brown pigment deposition in parenchymal liver cells.


syndromic X-linked intellectual disability Lubs type

Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations vary widely depending on the gender of the patient and on the gene content of the duplicated segment. The prevalence of Xq duplications remains unknown.


Sertoli cell-only syndrome

Sertoli cell-only syndrome (SCO syndrome) is a cause of male infertility. In SCO syndrome, only Sertoli cells (cells that nurture the immature sperm) line the seminiferous tubules (tubes inside the testicles where sperm develop). Therefore, there are not any sperm cells present in the seminiferous tubules. Men typically learn they are affected between ages 20-40 years when being evaluated for infertility and are found to have no sperm production (azoospermia). Other signs and symptoms are rare, but in some cases there could be an underlying cause of SCO syndrome that causes other symptoms, such as Klinefelter syndrome. Most cases of SCO syndrome are idiopathic (of unknown cause), but causes may include deletions of genetic information on regions of the Y-chromosome, especially on the azoospermia factor (AZF) region of Y-chromosome. Other causes include exposure to chemicals or toxins, history of radiation therapy, and history of severe trauma. Diagnosis of SCO syndrome is confirmed with testicular biopsy. Although there is currently no effective treatment, assisted reproductive technology may assist some men with SCO syndrome in being able to have children.


Immunodeficiencies Affecting Cellular and Humoral Immunity - Severe Combined Immune Deficiency

A group of immunodeficiency disorders that include T cell-negative, B cell-positive severe combined immunodeficiencies; and T cell-negative, B cell-negative severe combined immunodeficiencies.


trisomy 13

Trisomy 13 is a chromosomal anomaly caused by the presence of an extra chromosome 13 and is characterized by brain malformations (holoprosencephaly), facial dysmorphism, ocular anomalies, postaxial polydactyly, visceral malformations (cardiopathy) and severe psychomotor retardation.


Eisenmenger syndrome

Eisenmenger syndrome (ES) is an form of pulmonary arterial hypertension (PAH) associated with unoperated congenital heart disease and is characterized by congenital heart malformations with reversed or bi-directional shunting through an intra-cardiac or intervascular (usually aorto-pulmonary) communication with the development of PAH.


Cockayne syndrome type 2

Cockayne syndrome caused by mutation(s) in the ERCC6 gene, encoding DNA excision repair protein ERCC-6.


Scheie syndrome

Scheie syndrome is the mildest form of mucopolysaccharidosis type 1 (MPS1), a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.


fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia.


Ehlers-Danlos syndrome, arthrochalasis type

Arthrochalasia Ehlers-Danlos syndrome (aEDS) is an inherited connective tissue disorder that is caused by defects in a protein called collagen. Common symptoms include severe joint hypermobility ; congenital hip dislocation; fragile, hyperextensible skin; hypotonia ; and kyphoscoliosis (kyphosis and scoliosis). EDS, arthrochalasia type is caused by changes (mutations) in the COL1A1 gene or the COL1A2 gene and is inherited in an autosomal dominant manner. Treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.


Rubinstein-Taybi syndrome due to CREBBP mutations

Any Rubinstein-Taybi syndrome in which the cause of the disease is a mutation in the CREBBP gene.


Bartsocas-Papas syndrome 1

A rare, inherited, popliteal pterygium syndrome characterized by severe popliteal webbing, microcephaly, a typical face with short palpebral fissures, ankyloblepharon, hypoplastic nose, filiform bands between the jaws and facial clefts, oligosyndactyly, genital abnormalities, and additional ectodermal anomalies (i.e. absent hair, eyebrows, lashes, nails). It is often fatal in the neonatal period, but patients living until childhood have been reported.


Papillon-Lefevre disease

Papillon-Lefevre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.


Severe Combined Immunodeficiency with Absence of T and B Cells

An inherited, severe immunodeficiency disorder characterized by abnormalities in the development and function of T and B cell immunity. The peripheral T and B lymphocytes are absent or in very low counts.


Kluver-Bucy syndrome

Kluver Bucy syndrome is a rare behavioral impairment characterized byinappropriate sexual behaviors and mouthing of objects. Other signs and symptoms, includea diminished ability to visually recognize objects,loss of normal fear and anger responses, memory loss, distractibility, seizures, and dementia. It is associated with damage to the anterior temporal lobes of the brain. Cases have been reported in association with herpes encephalitis and head trauma. Treatment is symptomatic and may include the use of psychotropic medications.


polymyositis in scleroderma

A rare autoimmune disorder in which patients present with overlapping symptoms of systemic scleroderma and polymyositis or dermatomyositis.


pyogenic arthritis-pyoderma gangrenosum-acne syndrome

A rare pleiotropic autoinflammatory disorder of childhood, primarily affecting the joints and skin.


Decreased or absent levels of serum immunoglobulin A, with normal serum levels of immunoglobulin G and immunoglobulin M in a patient who is older than 4 years of age and in whom all other causes of hypogammaglobulinemia have been excluded. Affected individuals may be asymptomatic or have frequent infections, allergic reactions, or autoimmune disorders.


striatonigral degeneration

A progressive neurodegenerative disorder caused by a disruption in the connection between the striatum and the substantia nigra. It is a type of multiple system atrophy (MSA). Signs and symptoms include rigidity, instability, impaired speech, and slow movements.


Predominantly Antibody Deficiencies

A group of primary immunodeficiency diseases caused predominantly by antibody deficiencies, comprised of: Agammaglobulinemia with absent B cells; Severe reduction in at least two serum immunoglobulins, common variable immunodeficiency (CVID) phenotype; Severe reduction in serum IgG and IgA with normal or elevated IgM, hyper-IgM; and Isotype, light chain, or functional deficiencies with generally normal numbers of B cells.


Stickler syndrome type 1

Stickler syndrome inherited in an autosomal dominant pattern, caused by mutation(s) in the COL2A1 gene, encoding collagen alpha-1(II) chain.


Evans syndrome

Evans syndrome is a rare chronic hematologic disorder characterized by the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA; a disorder in which auto-antibodies are directed against red blood cells causing anemia of varying degrees of severity) with immune thrombocytopenic purpura (ITP; a coagulation disorder in which auto-antibodies are directed against platelets causing hemorrhagic episodes) and occasionally autoimmune neutropenia, in the absence of a known underlying etiology.


Paraneoplastic Subacute Sensory Neuronopathy

A sensory neuropathy caused by the effects of a distant neoplasm (usually a small cell carcinoma). It is usually caused by the production of anti-neuronal autoantibodies: anti-Hu (ANNA-1) or anti-CV2 (CRMP-5), which result in cytotoxic T-cell mediated destruction of dorsal root ganglia. It is the most common clinical presentation of paraneoplastic encephalomyelitis. Clinical signs include asymmetric paresthesia of the face, trunk and proximal extremities followed by lancinating pain, vibrioceptive and proprioceptive impairment, and muted reflexes. Clinical course usually follows a progressive neurologic deterioration which stabilizes at a level of severe, permanent disability.


Type II Refractory Celiac Disease

Refractory celiac disease associated with abnormal (clonal) intraepithelial lymphocyte phenotype. It is a precursor of enteropathy-associated T-cell lymphoma.


Refractory Thrombocytopenia

A myelodysplastic syndrome characterized by the presence of at least 10% dysplastic megakaryocytes, found within at least 30 megakaryocytes examined in the bone marrow.


cryopyrin-associated periodic syndrome

Cryopyrin associated periodic syndrome (CAPS) defines a group of autoinflammatory diseases, characterized by recurrent episodes of systemic inflammatory attacks in the absence of infection or autoimmune disease. CAPS comprises 3 disorders on a continuum of severity: severe CINCA syndrome, intermediate Muckle-Wells syndrome (MWS) and milder familial cold urticaria (FCAS).


Myelodysplastic Syndrome, Not Otherwise Specified

Myelodysplastic syndrome with low blasts characterized by the absence of defining genetic abnormalities.


Neurofibromatosis aggravated

A condition causing exacerbation of the clinical features of neurofibromatosis.


acute motor axonal neuropathy

Acute motor axonal neuropathy (AMAN) is a pure motor axonal form of Guillain-Barre syndrome (GBS).


ring chromosome 13

Ring chromosome 13 is a chromosomal anomaly of chromosome 13 characterized by a widely variable phenotype (ranging from mild to severe) principally characterized by intrauterine growth retardation, developmental delay, short stature, moderate to severe intellectual deficit, microcephaly, facial dysmorphism (i.e. upslanting palpebral fissures, hypertelorism, abnormal ears, broad nasal bridge, high arched palate, micrognathia, small mouth, and thin lips), hands and feet anomalies, and genital abnormalities. Additional features reported include behavioral problems, hearing and speech disorders, congenital heart defects, cerebral malformations, and anal atresia.


congenital myasthenic syndrome

Congenital myasthenic syndrome (CMS) is a group of genetic disorders of impaired neuromuscular transmission at the motor endplate characterized by fatigable muscle weakness.


Cornelia de Lange syndrome 2

An X-linked inherited form of Cornelia De Lange syndrome caused by mutations in the SMC1A gene mapped to chromosome Xp11.22. Patients have a milder form of the syndrome compared to patients with the NIPBL gene mutation.


C1Q deficiency

C1q deficiency is a rare disorder associated with recurrent skin lesions, chronic infections, systemic lupus erythematosus (SLE) or SLE-like diseases. It has also been associated with a kidney disease known as mesangial proliferative glomerulonephritis. C1q is a complex and together with other proteins, C1r and C1s, it forms the C1 complex. This complex is important for the activation of the complement system (a group of proteins that work with the immune system). It also disposes cells that are dead. C1q deficiency presents in 2 different forms, absent C1q protein or abnormal C1q protein. Symptoms include infections (ear infections (otitis media), meningitis, urinary tract infections, oral infections); skin lesions (small blisters (vesicles), dark patches, and atrophic areas) that get worse upon light exposure; cataracts; loss of eyelashes, eyebrows, and scalp hair; blood in urine; and glomerulonephritis. About 93% of cases are associated with systemic lupus erythematosus. It can be caused by mutations in the C1QA, C1QB or C1QC genes and is inherited in an autosomal recessive pattern. Treatment depends on the symptoms. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation, a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor.


Bruton-type agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, and is characterized in affected males by recurrent bacterial infections during infancy.


IFN-gamma Receptor 1 Deficiency

A condition of decreased or absent presence or activity of interferon gamma receptor 1. Deficiency of this protein is associated with immunodeficiency 27A and immunodeficiency 27B.


de novo Myelodysplastic Syndrome

A primary myelodysplastic syndrome not associated with prior radiation or chemotherapy treatment.


fetal valproate syndrome

Fetal valproate syndrome (FVS), is an anticonvulsant drug-related embryofetopathy that can occur when a fetus is exposed to valproic acid (VPA), characterized by distinct facial dysmorphism, congenital anomalies and developmental delay (especially in language and communication).


syndromic X-linked intellectual disability 5

X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (XDIBS), or Pettigrew syndrome is a central nervous system malformation characterized by severe intellectual deficit, early hypotonia with progression to spasticity and contractures, choreoathetosis, seizures, dysmorphic face (long face with prominent forehead), and brain imaging abnormalities such as Dandy-Walker malformation, and iron deposition.


Parana hard-skin syndrome

A rare disorder characterized by rigid, thick skin that covers the entire body and affects movements. The movement of the chest and abdomen is severely restricted. Affected individuals develop respiratory insufficiency which may lead to death.


tempi syndrome

TEMPI syndrome is a rare multi-systemic disease characterized by the presence of Telangiectasias, Erythrocytosis with elevated erythropoietin levels, Monoclonal gammopathy, Perinephric-fluid collections, and Intrapulmonary shunting.


Fanconi anemia complementation group D2

Fanconi anemia caused by mutations of the FANCD2 gene. This gene is involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing.


Griscelli syndrome type 2

Griscelli syndrome type 2 (GS2) is a rare, inherited condition that affects the skin, hair, and immune system. People with GS2 have unusually light skin and silver-colored hair. They are also prone to recurrent infections and develop an immune condition called hemophagocytic lymphohistiocytosis (HLH). HLH can damage organs and tissues throughout the body, causing life-threatening complications. GS2 is caused by changes (mutations) in the RAB27A gene and is inherited in an autosomal recessive manner. The only current treatment that can extend survival is stem cell transplantation (a bone marrow transplant). Untreated, most children with GS2 do not survive past early childhood.


Opitz G/BBB syndrome

Opitz G/BBB syndrome (OS) is a multiple congenital anomalies disorder characterized by malformations of the midline including hypertelorism, laryngo-tracheo-esophalgeal defects and hypospadias. There are two clinically indistinguishable genetic subtypes of Opitz G/BBB: X-linked Opitz G/BBB syndrome (XLOS), and autosomal dominant Opitz G/BBB syndrome (ADOS).


Myhre syndrome

Myhre syndrome is characterized by striking muscular build, short stature, reduced joint mobility, brachydactyly, mixed hearing loss and mental retardation of variable severity. Facial dysmorphism with short palpebral fissures, short philtrum, thin lips, maxillary hypoplasia and prognathism is present. Thick skin has been observed in six patients.


Myelodysplastic Syndrome/Acute Myeloid Leukemia with Myelodysplasia-Related Gene Mutations

Myelodysplastic syndromes/acute myeloid leukemias characterized by the presence of gene mutations that are associated with myelodysplasia.


long QT syndrome 14

Any long QT syndrome in which the cause of the disease is a mutation in the CALM1 gene.


acrocephalosyndactyly

Acrocephalosyndactyly (ACS) syndromes represent a group of inherited congenital malformation disorders characterized by craniosynostosis and fusion or webbing of the fingers or toes, often with other associated manifestations.


severe combined immunodeficiency due to CD70 deficiency

A rare primary immunodeficiency caused by homozygous CD70 mutation. It is characterized by susceptibility to Epstein-Barr virus infection, hypogammaglobulinemia, and development of B-cell non-Hodgkin lymphomas and Hodgkin lymphomas.


mitochondrial DNA depletion syndrome 4a

Alpers Huttenlocher syndrome (AHS) is a cerebrohepatopathy and a rare and severe form of mitochondrial DNA (mtDNA) depletion syndrome characterized by the triad of progressive developmental regression, intractable seizures, and hepatic failure.


proteasome-associated autoinflammatory syndrome 1

An autosomal recessive condition caused by mutation(s) in the PSMB8 gene, encoding proteasome subunit beta type-8. It is characterized by early onset annular erythematous plaques, partial lipodystrophy, and recurrent fever.


CODAS syndrome

Codas syndrome is a multiple congenital anomalies syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies.


DNA ligase IV deficiency

LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).


congenital myasthenic syndrome 5

Congenital myasthenic syndrome caused by mutation(s) in the COLQ gene, encoding acetylcholinesterase collagenic tail peptide. It is inherited in an autosomal recessive manner.


transient hypogammaglobulinemia

A broad classification for humoral immunodeficiencies. These disorders may be caused by inadequate activation of progenitor B cells, defective class-switching or the effects of medications. Despite the potential for increased susceptibility to infection, these disorders are self-limited with eventual normalization of serum antibody levels.


Childhood Myelodysplastic Syndrome with Low Blasts, Not Otherwise Specified

Childhood myelodysplastic syndrome with low blasts in which further characterization is not available.


Vertiginous syndrome

A group of disorders characterized by the sensation of constant motion or spinning despite not moving.


Sandifer syndrome

Sandifer syndrome is a paroxysmal dystonic movement disorder occurring in association with gastro-oesophageal reflux, and, in some cases, hiatal hernia.


thoracic outlet syndrome

A syndrome resulting from the compression of the blood vessels or nerves in the space between the clavicle and first rib (thoracic outlet). It is caused by car accident injuries or repetitive job or sport-related injuries. Signs and symptoms include pain in the shoulders and neck, numbness in the fingers, and weakening grip.


epidermodysplasia verruciformis, susceptibility to, 4

An autosomal recessive condition caused by mutation(s) in the RHOH gene, encoding Rho-related GTP-binding protein RhoH. It presents in childhood and is characterized by defects in T-cell development and signaling leading to increased susceptibility to certain human papilloma viruses (HPV) that cause warty skin lesions that are unresponsive to treatment.


Fanconi anemia complementation group N

Any Fanconi anemia in which the cause of the disease is a mutation in the PALB2 gene.


trichothiodystrophy

Trichothiodystrophy or TTD is a heterogeneous group disorders characterized by short, brittle hair with low-sulphur content (due to an abnormal synthesis of the sulfur containing keratins).


selective IgG subclass deficiency

A classification of dysgammaglobulinemias characterized by low or undetectable serum levels of one of the four immunoglobulin class G (IgG) subclasses. Selective IgG1 deficiency is rare and primarily decreases the immune response to bacterial protein antigens. Selective IgG2 deficiency is the most common subclass deficiency among children and primarily leads to an inadequate response to bacterial polysaccharide antigens. Selective IgG3 deficiency is the most common subclass deficiency among adults and also primarily lowers the response to bacterial proteins. Selective IgG4 deficiency may be a clinically insignificant developmental variant, as IgG4 is a subclass that is virtually undetectable until the end of the first decade of life. Low levels of any IgG subclass will reduce the immune system's effectiveness and thus the clinical presentation of these diseases is usually recurrent infection, particularly by encapsulated bacteria.


Hermansky-Pudlak syndrome 2

A type of Hermansky-Pudlak syndrome (HPS), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and neutropenia.


Myelodysplastic Syndrome with Mutated TP53

Myelodysplastic syndrome characterized by the presence of TP53 gene mutations.


leukocyte adhesion deficiency type II

Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD characterized by recurrent bacterial infections, severe growth delay and severe intellectual deficit.


chromosome 16p12.1 deletion syndrome, 520kb

A condition caused by a 520 kb deletion at 16p12.1. It is characterized by developmental delay, craniofacial dysmorphology and congenital heart defects.


cauda equina syndrome with neurogenic bladder

A rare neurologic disorder caused by impingement of the nerve roots of the cauda equina secondary to disk herniation, spinal stenosis, vertebral fracture, neoplasm or infection. Clinical signs may include bladder or bowel dysfunction, paresthesia and weakness of the lower extremities. The development of neurogenic bladder implies that surgical decompression was either ineffective, delayed or not attempted.


classic dopamine transporter deficiency syndrome

Classic Dopamine Transporter Deficiency Syndrome describes a subset of SLC6A3-related DTDS cases which present in early infancy. This disorder is usually first identified by neonatal distress and irritability, feeding difficulties, and motor developmental delay.


fetal hydantoin syndrome

Fetal hydantoin syndrome is a drug-related embryofetopathy that can occur when an embryo/fetus is exposed to the anticonvulsant drug phenytoin, characterized by distinct craniofacial anomalies (hypertelorism and epicanthal folds, short nose and deep nasal bridge, malformed and low set ears, short neck) as well as hypoplastic distal phalanges and underdevelopment of nails of fingers and toes, prenatal and postnatal growth retardation, and neurological impairment (at a 2-3 times higher risk than that of the general population) including cognitive deficits and motor developmental delay. Less commonly, microcephaly, ocular defects, oral clefts, umbilical and inguinal hernias, hypospadias and cardiac anomalies have also been reported.


POEMS syndrome

POEMS syndrome is a paraneoplastic syndrome characterized by polyradiculoneuropathy (P), organomegaly (O), endocrinopathy (E), clonal plasma cell disorder (M), and skin changes (S). Other features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis, and elevated VEGF levels.


trisomy X

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX).


Refractory Neurofibromatosis Type 1

Neurofibromatosis type 1 that is resistant to treatment.


Fanconi anemia complementation group I

Fanconi anemia caused by mutations in the FANCI gene, encoding Fanconi anemia group I protein.


myelodysplastic syndrome associated with isolated del(5q)

A myelodysplastic syndrome characterized by a deletion between bands q31 and 33 on chromosome 5. The number of blasts in the bone marrow and blood is <5%. The bone marrow is usually hypercellular or normocellular with increased number of often hypolobated megakaryocytes. The peripheral blood shows macrocytic anemia. This syndrome occurs predominantly but not exclusively in middle age to older women. The prognosis is good and transformation to acute leukemia is rare. (WHO, 2001)


common variable immunodeficiency 11

An autosomal recessive subtype of common variable immunodeficiency caused by mutation(s) in the IL21 gene, encoding interleukin-21.


Alport syndrome

A rare renal disease characterized by glomerular nephropathy with hematuria progressing to end-stage renal disease (ESRD), frequently associated with sensorineural deafness, and occasionally with ocular anomalies.


neurofibromatosis 1

The most common type of neurofibromatosis.  It is characterized clinically by cutaneous and subcutaneous tumors with patches of hyperpigmentation. The hyperpigmented skin areas, are present from birth and found anywhere on the body surface.  They can vary markedly in size and color.  The dark brown areas are called cafe-au-lait spots. The multiple cutaneous and subcutaneous tumors are nerve sheath tumors, called neurofibromas.  They can develop anywhere along the peripheral nerve fibers. Neurofibromas can become quite large, causing a major disfigurement, eroding bone, and compressing various peripheral nerve structures.  Type 1 neurofibromatosis has dominant inheritance, with a gene locus on the proximal long arm of chromosome 17.


mismatch repair cancer syndrome

An autosomal dominant hereditary neoplastic syndrome caused by mutations in the PMS2, MLH1, MSH2, or APC genes. There are two types described, type 1, characterized by the presence of glioblastoma and often associated with hereditary nonpolyposis colorectal carcinoma, and type 2, characterized by the presence of medulloblastoma and familiar adenomatous polyposis.


orofaciodigital syndrome type 6

Joubert syndrome with orofaciodigital defect (or oral-facial-digital syndrome type 6, OFD6) is a very rare subtype of Joubert syndrome and related disorders (JSRD) characterized by the neurological features of JS associated with orofacial anomalies and often polydactyly.


complement component 3 deficiency

A rare genetic disorder with an autosomal recessive pattern of inheritance. It is caused by the ineffective or decreased biosynthesis of the third complement component, C3. C3 deficiency may also be acquired acutely post-infection or chronically from co-morbid autoimmune disorders. If C3 is adequately synthesized, its rapid depletion may result in a functional deficiency. Clinical signs of the inherited deficiency present within the first decade of life and are consistent with the signs of recurrent systemic infection or immune complex disease. Deficiency of serum C3 and its major cleavage product, C3b, will decrease the effective humoral immune response to encapsulated bacteria. Deficiency of C3 also impairs clearance of circulating immune complexes and therefore predisposes to rheumatic and renal disease.


Congenital iodine deficiency syndrome of mixed type

Congenital iodine deficiency syndrome associated with overlapping features of both the neurological and myxedematous variants.


developmental defect during embryogenesis

A disease that has its basis in the disruption of embryonic morphogenesis.


MHC class I deficiency

Immunodeficiency by defective expression of HLA class 1 is a very rare, primary, genetic, immunodeficiency disorder characterized by partial or complete absence of human leukocyte antigen class I expression resulting in a non-specific clinical picture of impaired immune response and susceptibility to infections.


multiple system atrophy

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure (cardiovascular and/or urinary), parkinsonism, cerebellar impairment and corticospinal signs with a median survival of 6-9 years.


Williams syndrome

A rare genetic multisystemic neurodevelopmental disorder characterized by a distinct facial appearance, cardiac anomalies (most frequently supravalvular aortic stenosis), cognitive and developmental abnormalities, and connective tissue abnormalities (such as joint laxity)


Genitourinary syndrome of menopause

A spectrum of lower urogenital tract signs and symptoms that are associated with the decreased production of estrogen experienced during menopause.  Findings may include genital dryness, burning or irritation, dyspareunia, decreased libido, urinary urgency, dysuria and recurrent urinary tract infections.


cerebrooculofacioskeletal syndrome 4

Any COFS syndrome in which the cause of the disease is a mutation in the ERCC1 gene.


Miller-Dieker lissencephaly syndrome

A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.


T-B+ severe combined immunodeficiency due to JAK3 deficiency

Severe combined immunodeficiency (SCID) T-B+ due to JAK3 deficiency is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.


lymphoproliferative syndrome 1

A condition of decreased or absent presence or activity of IL2-inducible t-cell kinase. Deficiency of this protein is associated with lymphoproliferative syndrome 1, an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia..


Rare Neoplastic Syndrome

A broad classification for uncommon disorders in which the development of neoplasms occur in association with a characteristic set of signs or symptoms. These disorders commonly have a genetic basis. The types of neoplasms themselves are not necessarily uncommon.


Ogden syndrome

Ogden syndrome is a rare, genetic progeroid syndrome characterized by a variable phenotype including postnatal growth delay, severe global developmental delay, hypotonia, non-specific dysmorphic facies with aged appearance and cryptorchidism, as well as cardiac arrthymias and skeletal anomalies. Patients typically present with widely opened fontanels, mainly truncal hypotonia, a waddling gait with hypertonia of the extremities, small hands and feet, broad great toes, scoliosis and redundant skin with lack of subcutaneous fat.


The HDR syndrome is an inherited condition consisting of hypoparathyroidism, sensorineural deafness and renal disease.