900
(39.9%)

congenital disorder of glycosylation with defective fucosylation 1

Feeding difficulties Hirsutism Hypoglycemia Neutropenia

Autosomal recessive inheritance

902
(39.4%)

Aicardi-Goutieres syndrome 5

Dry skin Feeding difficulties in infancy Microcephaly Thrombocytopenia

Autosomal recessive inheritance

Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the SAMHD1 gene.

902
(39.4%)

MPDU1-CDG

Abnormality of the coagulation cascade Dry skin Feeding difficulties Microcephaly

Autosomal recessive inheritance

The CDG (Congenital Disorders of Glycosylation) syndromes are a group of autosomal recessive disorders affecting glycoprotein synthesis. CDG syndrome type If is characterised by psychomotor delay, seizures, failure to thrive, and cutaneous and ocular anomalies.

902
(39.4%)

Down syndrome

Anal atresia Macroglossia Myeloproliferative disorder Single transverse palmar crease

Sporadic

Down syndrome is a chromosomal abnormality caused by the presence of a third (partial or total) copy of chromosome 21 and that is characterized by variable intellectual disability, muscular hypotonia, and joint laxity, often associated with a characteristic facial dysmorphism and various anomalies such as cardiac, gastrointestinal, or endocrine defects.

902
(39.4%)

Cohen syndrome

Feeding difficulties in infancy Neutropenia Open mouth Single transverse palmar crease

Autosomal recessive inheritance

Cohen syndrome (CS) is a rare genetic developmental disorder characterized by microcephaly, characteristic facial features, hypotonia, non-progressive intellectual deficit, myopia and retinal dystrophy, neutropenia and truncal obesity.

906
(39.4%)

autosomal recessive congenital ichthyosis 4A

Abnormal abdomen morphology Ectropion Palmoplantar keratoderma

Autosomal recessive inheritance

Any autosomal recessive congenital ichthyosis in which the cause of the disease is a mutation in the ABCA12 gene.

906
(39.4%)

Acrootoocular syndrome

Abnormal abdomen morphology Narrow palate Numerous nevi

Autosomal recessive inheritance

Acro-oto-ocular syndrome is a very rare disorder associating pseudopapilledema (optic disc swelling not secondary to increased intracranial pressure), mixed hearing loss, facial dysmorphism and limb extremity anomalies.

908
(39.0%)

sulfhemoglobinemia, congenital

Abnormality of blood and blood-forming tissues Cyanosis

Autosomal dominant inheritance

909
(39.0%)

congenital diarrhea 6

Diarrhea Vitamin B12 deficiency

Autosomal dominant inheritance

Any congenital diarrhea in which the cause of the disease is a mutation in the GUCY2C gene.

909
(39.0%)

maternal riboflavin deficiency

Low levels of vitamin B2 Metabolic acidosis Poor suck

Autosomal dominant inheritance

909
(39.0%)

methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

Failure to thrive Gastroesophageal reflux Methylmalonic acidemia

Autosomal recessive inheritance

Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency is a rare inborn error of metabolism disease characterized by mild to moderate, persistent elevation of methylmalonic acid in plasma, urine and cerebrospinal fluid. Clinical presentation may include acute metabolic decompensation with metabolic acidosis (presenting with vomiting, dehydration, confusion, hallucinations), nonspecific neurological symptoms, or may also be asymptomatic.

909
(39.0%)

mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Feeding difficulties in infancy Methylmalonic acidemia Sensorineural hearing impairment

Autosomal recessive inheritance

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterised by the association of a mitochondrial encephalomyopathy and an aminoacidopathy. It has been described in two brothers presenting with developmental delay, neurological signs, deafness, exercise intolerance, lactic acidosis and elevation of several plasmatic amino acids. Mitochondria morphology was found to be abnormal on muscle biopsy. Transmission is likely to be linked to maternal mitochondrial DNA.

913
(39.0%)

lung disease, immunodeficiency, and chromosome breakage syndrome;

Abnormality of the thymus Eczema Increased sensitivity to ionizing radiation Wide anterior fontanel

Autosomal recessive inheritance

914
(38.9%)

congenital bile acid synthesis defect 6

Low levels of vitamin D Steatorrhea Vertical supranuclear gaze palsy

Autosomal recessive inheritance

Any congenital bile acid synthesis defect in which the cause of the disease is a mutation in the ACOX2 gene.

915
(38.9%)

circumvallate placenta syndrome

Abnormality of the skeletal system Abnormality of the skin Intracranial hemorrhage

Autosomal recessive inheritance

915
(38.9%)

combined immunodeficiency due to DOCK8 deficiency

Eczema Eosinophilia Subarachnoid hemorrhage

Autosomal recessive inheritance

Combined immunodeficiency due to dedicator of cytokinesis 8 protein (DOCK8) deficiency is a form of T and B cell immunodeficiency characterized by recurrent cutaneous viral infections, susceptibility to cancer and elevated serum levels of immunoglobulin E (IgE).

917
(38.9%)

Wiskott-Aldrich syndrome 2

Eczema Reduced natural killer cell activity Thrombocytopenia

Autosomal recessive inheritance

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

917
(38.9%)

combined immunodeficiency due to moesin deficiency

Decreased circulating antibody level Eczema Neutropenia Recurrent urinary tract infections

X-linked recessive inheritance

917
(38.9%)

WHIM syndrome

Decreased circulating antibody level Neutropenia Verrucae

Autosomal dominant inheritance

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a congenital autosomal dominant immune deficiency characterized by abnormal retention of mature neutrophils in the bone marrow (myelokathexis) and occasional hypogammaglobulinemia, associated with an increased risk for bacterial infections and a susceptibility to human papillomavirus (HPV) induced lesions (cutaneous warts, genital dysplasia and invasive mucosal carcinoma).

920
(38.7%)

Onychotrichodysplasia and neutropenia

Chronic irritative conjunctivitis Concave nail Intellectual disability, mild Neutropenia

Autosomal recessive inheritance

920
(38.7%)

Noonan syndrome 2

Coarctation of aorta Cryptorchidism Curly hair Leukemia

Autosomal recessive inheritance

920
(38.7%)

vertebral anomalies and variable endocrine and T-cell dysfunction

Abnormal B cell morphology Cleft palate Glabellar hemangioma Low anterior hairline

Autosomal dominant inheritance

923
(38.6%)

Meige disease

Cleft palate Facial edema Hypoplasia of lymphatic vessels Yellow nails

Autosomal dominant inheritance

Meige disease is a frequent form of late-onset, primary lymphedema characterized by lower limb lymphedema typically developing during puberty.

923
(38.6%)

yellow nail syndrome

Hypoplasia of lymphatic vessels Lymphedema Slow-growing nails

Autosomal dominant inheritance

Yellow nail syndrome (YNS) is a very rare syndromic disorder characterized by the variable triad of characteristic yellow nails, chronic respiratory manifestations, and primary lymphedema.

923
(38.6%)

Dahlberg-Borer-Newcomer syndrome

Hypertrichosis Lymphedema Pulmonary lymphangiectasia Renal insufficiency

Autosomal recessive inheritance

Dahlberg-Borer-Newcomer syndrome is a very rare ectodermal dysplasia syndrome, described in 2 adult brothers, characterized by the association of hypoparathyroidism, nephropathy, congenital lymphedema, mitral valve prolapse and brachytelephalangy. Additional features include mild facial dysmorphism, hyperthricoses, and nail abnormalities.

926
(38.6%)

pulmonary arteriovenous malformation (disease)

Cyanosis Pulmonary arteriovenous fistulas

Autosomal recessive inheritance

Pulmonary arteriovenous malformation (PAVM) describes an anatomic communication between a pulmonary artery and a pulmonary vein leading to a right to left extracardiac shunt that can be asymptomatic or can lead to varying manifestations such as dyspnea, hemoptysis, and neurological symptoms.

926
(38.6%)

atrioventricular septal defect 3

Cyanosis Hypertension Pulmonary arterial hypertension

Autosomal dominant inheritance

Any atrioventricular septal defect in which the cause of the disease is a mutation in the GJA1 gene.

926
(38.6%)

hemangiomatosis, cutaneous, with associated features

Acrocyanosis Hemangiomatosis Hypertelorism

Autosomal recessive inheritance

926
(38.6%)

Coffin-Lowry syndrome

Acrocyanosis Cutis marmorata Inguinal hernia

X-linked dominant inheritance Sporadic

Coffin-Lowry syndrome (CLS) is a rare genetic neurological disorder characterized by psychomotor and growth retardation, facial dysmorphism, digit abnormalities, and progressive skeletal changes.

930
(38.6%)

leukocyte adhesion deficiency type II

Abnormality of metabolism/homeostasis Recurrent otitis media Reduction of neutrophil motility Widow's peak

Autosomal recessive inheritance

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

931
(38.5%)

desquamative interstitial pneumonia

Abnormality of metabolism/homeostasis Cyanosis Recurrent upper respiratory tract infections

Autosomal recessive inheritance

A rare idiopathic interstitial pneumonia characterized by accumulation of macrophages in alveolar spaces and interstitial inflammation. It usually occurs in smokers. Some patients develop progressive interstitial lung fibrosis.

932
(38.5%)

cardiomyopathy-hypotonia-lactic acidosis syndrome

Cyanosis Hypertrophic cardiomyopathy Metabolic acidosis

Autosomal recessive inheritance

Cardiomyopathy-hypotonia-lactic acidosis syndrome is characterised by hypertrophic cardiomyopathy, muscular hypotonia and the presence of lactic acidosis at birth. It has been described in two sisters (both of whom died within the first year of life) from a nonconsanguineous Turkish family. The syndrome is caused by a homozygous point mutation in the exon 3A of the SLC25A3 gene encoding a mitochondrial membrane transporter.

932
(38.5%)

microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome

Acrocyanosis Bradycardia Glucose intolerance Thick lower lip vermilion

Autosomal recessive inheritance

Microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome is a rare, genetic congenital anomalies/dysmorphic syndrome characterized by growth failure, global developmental delay, profound intellectual disability, autistic behaviors, acquired second-degree heart block with bradycardia and vasomotor instability. Hands and feet present with long fusiform fingers, campto-clinodactyly and crowded toes while craniofacial dysmorphism includes microcephaly, broad forehead, thin eyebrows, upslanting palpebral fissures, large ears with prominent antihelix, prominent nose, long philtrum, thin upper lip vermillion and prominent lower lip. Neurological signs include hypotonia, brisk reflexes, dystonic-like movements and truncal ataxia and imaging shows cerebellar hypoplasia and simplified gyral pattern.

934
(38.5%)

hereditary neurocutaneous angioma

Gastrointestinal hemorrhage Hemangioma Hematuria

Autosomal dominant inheritance

Hereditary neurocutaneous angioma is characterised by the association of cerebral and cutaneous angiomatous lesions. It has been described in less than 10 families. Clinical manifestations of the cerebral lesions include epilepsy, cerebral haemorrhage, and focal neurological deficit. Transmission is autosomal dominant.

934
(38.5%)

isovaleric acidemia

Cerebellar hemorrhage Metabolic acidosis Thrombocytopenia Vomiting

Autosomal recessive inheritance

Isovaleric acidemia (IVA) is an autosomal recessively inherited organic aciduria characterized by a deficiency in isovaleryl-CoA dehydrogenase, that has wide clinical variability and that can present in infancy with acute manifestations of vomiting, failure to thrive, seizures, lethargy, a characteristic ''sweaty feet'' odor, acute pancreatitis and mild to severe developmental delay or in childhood with metabolic acidosis (brought on by prolonged fasting, an increased intake of protein-rich food or infections) and that can be fatal if not treated immediately. Chronic intermittent presentations and asymptomatic patients have also been reported.

934
(38.5%)

severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive

Conjunctivitis Diarrhea Panhypogammaglobulinemia T lymphocytopenia

Autosomal recessive inheritance

Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.

934
(38.5%)

autosomal recessive agammaglobulinemia 1

Agammaglobulinemia Conjunctivitis Diarrhea Neutropenia

Autosomal recessive inheritance

934
(38.5%)

ALG12-CDG

Feeding difficulties Hypocalcemia Patent ductus arteriosus Prolonged partial thromboplastin time

Autosomal recessive inheritance

A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. The disease is caused by loss of function mutations of the gene ALG12 (22q13.33).

939
(38.4%)

DDOST-CDG

Decreased liver function Strabismus Type I transferrin isoform profile

Autosomal recessive inheritance

DDOST-CDG is a form of congenital disorders of N-linked glycosylation characterized by failure to thrive, developmental delay, hypotonia, strabismus and hepatic dysfunction. The disease is caused by mutations in the gene DDOST (1p36.1).

939
(38.4%)

STT3A-CDG

Abnormal glycosylation Feeding difficulties Microcephaly

Autosomal recessive inheritance

STT3A-CDG is a form of congenital disorders of N-linked glycosylation characterized by developmental delay, intellectual disability, failure to thrive, hypotonia and seizures. STT3A-CDG is caused by mutations in the gene STT3A (11q23.3).

939
(38.4%)

ALG11-CDG

Microcephaly Type I transferrin isoform profile Vomiting

Autosomal recessive inheritance

A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (microcephaly, high forehead, low posterior hairline, strabismus), hypotonia, failure to thrive, intractable seizures, developmental delay, persistent vomiting and gastric bleeding. Additional features that may be observed include fat pads anomalies, inverted nipples, and body temperature oscillation. The disease is caused by mutations in the gene ALG11 (13q14.3).

942
(38.4%)

sporadic porphyria cutanea tarda

Fragile skin Hepatic fibrosis Hyperpigmentation of the skin Porphyrinuria

Autosomal dominant inheritance Heterogeneous

An instance of porphyria cutanea tarda that is acquired during the lifetime of the individual.

942
(38.4%)

multiple endocrine neoplasia type 1

Abnormality of the thyroid gland Hypoglycemia Pancreatic islet cell adenoma Subcutaneous lipoma

Autosomal dominant inheritance

Multiple endocrine neoplasia Type 1 (MEN1) is a frequent form of MEN, a rare inherited cancer syndrome, characterized by the development of neuroendocrine tumors of the parathyroid, pancreas, and anterior pituitary gland, and less commonly the adrenal cortical gland, with other non-endocrine tumors in some patients.

942
(38.4%)

partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome

Abnormality of the face Insulin resistance Lack of facial subcutaneous fat Pancreatitis

Autosomal dominant inheritance

942
(38.4%)

PPARG-related familial partial lipodystrophy

Cirrhosis Insulin-resistant diabetes mellitus Polycystic ovaries Prominent superficial veins

Autosomal dominant inheritance

942
(38.4%)

Williams syndrome

Diabetes mellitus Portal hypertension Premature graying of hair Recurrent urinary tract infections

Autosomal dominant inheritance

Williams syndrome is 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)

947
(38.3%)

gluthathione peroxidase deficiency

Compensated hemolytic anemia Neonatal hyperbilirubinemia

Autosomal recessive inheritance

947
(38.3%)

hemolytic anemia due to pyrimidine 5' nucleotidase deficiency

Hemoglobinuria Hemolytic anemia

Autosomal recessive inheritance

Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency is a rare, hereditary, hemolytic anemia due to an erythrocyte nucleotide metabolism disorder characterized by mild to moderate hemolytic anemia associated with basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. Patients present with variable features of jaundice, splenomegaly, hepatomegaly, gallstones, and sometimes require transfusions. Rare cases of mild development delay and learning difficulties are reported.

947
(38.3%)

anemia, nonspherocytic hemolytic, associated with abnormality of red cell membrane

Abnormality of metabolism/homeostasis Nonspherocytic hemolytic anemia

Autosomal recessive inheritance

947
(38.3%)

Heinz body anemia

Abnormality of metabolism/homeostasis Nonspherocytic hemolytic anemia

Autosomal dominant inheritance

947
(38.3%)

glutathione synthetase deficiency without 5-oxoprolinuria

Glyoxalase deficiency Hemolytic anemia

Autosomal recessive inheritance

947
(38.3%)

sideroblastic anemia 2

Decreased mean corpuscular volume Hypochromia Increased circulating ferritin concentration

Autosomal recessive inheritance Heterogeneous

947
(38.3%)

Diamond-Blackfan anemia 13

Elevated red cell adenosine deaminase level Normocytic anemia

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS29 gene.

947
(38.3%)

gamma-glutamylcysteine synthetase deficiency

Abnormality of metabolism/homeostasis Hemolytic anemia Polyneuropathy

Autosomal recessive inheritance

Gamma-glutamylcysteine synthetase deficiency is principally characterized by hemolytic anemia, (usually rather mild), however, the presence of neurological symptoms has also been reported.

947
(38.3%)

familial juvenile hyperuricemic nephropathy type 2

Anemia Hyperuricemia Renal hypoplasia

Autosomal dominant inheritance

Familial juvenile hyperuricemic nephropathy type 2 is a rare autosomal dominantly inherited disease of childhood characterized by hypoproliferative anemia, hyperuricemia and slowly progressing kidney failure due to dysregulation of the renin-angiotensin system (RAS).

947
(38.3%)

primary CD59 deficiency

Hemolytic anemia Paroxysmal nocturnal hemoglobinuria Polyneuropathy

Autosomal recessive inheritance

947
(38.3%)

hyperlysinemia (disease)

Abnormality of the genitourinary system Anemia Hyperlysinemia

Autosomal recessive inheritance

Hyperlysinaemia is a lysine metabolism disorder characterised by elevated levels of lysine in the cerebrospinal fluid and blood. Variable degrees of saccharopinuria are also present.

947
(38.3%)

X-linked sideroblastic anemia with ataxia

Abnormality of metabolism/homeostasis Dysarthria Sideroblastic anemia

X-linked recessive inheritance

X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare syndromic, inherited form of sideroblastic anemia in which the cause of the disease is a mutation in the ABCB7 gene and is characterized by mild to moderate anemia (with hypochromia and microcytosis) and early-onset, non- or slowly progressive spinocerebellar ataxia.

947
(38.3%)

aceruloplasminemia

Anemia Diabetes mellitus Torticollis

Autosomal recessive inheritance

Aceruloplasminemia is an adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.

947
(38.3%)

growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome

Increased serum lactate Macrocytic anemia Visual impairment

Autosomal recessive inheritance

Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the SFXN4 gene.

947
(38.3%)

glycogen storage disease due to phosphoglycerate kinase 1 deficiency

Exercise-induced myoglobinuria Hemolytic anemia Renal insufficiency

X-linked recessive inheritance

Phosphoglycerate kinase (PGK) deficiency is a metabolic disorder characterized by variable combinations of nonspherocytic hemolytic anemia, myopathy, and various central nervous system abnormalities.

947
(38.3%)

autosomal dominant Kenny-Caffey syndrome

Anemia Hypocalcemia Macrocephaly

Autosomal dominant inheritance

An autosomal dominant form of Kenny-Caffey Syndrome due to mutation(s) in the FAM111A gene, encoding protein FAM111A. This condition is characterized by transient hypocalcemia, delayed closure of the anterior fontanel, eye anomalies, including microphthalmia, proportionate short stature, and cortical thickening and medullary stenosis of the tubular bones.

947
(38.3%)

mitochondrial complex III deficiency nuclear type 8

Anemia Increased serum lactate Optic disc pallor

Autosomal recessive inheritance

Any mitochondrial complex III deficiency in which the cause of the disease is a mutation in the LYRM7 gene.

964
(38.1%)

abnormal neutrophil chemotactic response

Abnormal leukocyte morphology Congenital ichthyosiform erythroderma Eczema

964
(38.1%)

linear and whorled nevoid hypermelanosis

Eosinophilia Hyperpigmented streaks

Autosomal dominant inheritance Sporadic

Linear and whorled nevoid hypermelanosis (LWNH) is a rare skin condition characterized by swirling streaks of hyperpigmented (darkened) skin. The pigmentation follows the lines of Blashko and is mainly located on the trunk and limbs. It is present at birth or appears in the first few weeks of life. It typically progresses for one to two years and then stabilizes. Hyperpigmentation is usually the only symptom but there are isolated reports of other symptoms, involving mostly the central nervous system, musculoskeletal system, and heart. While most cases of LWNH are sporadic, apparent genetic transmission rarely has been described. A few people with LWNH have been diagnosed with chromosomal mosaicism.

964
(38.1%)

Hermansky-Pudlak syndrome 9

Hypopigmentation of the skin Leukopenia Thrombocytopenia

Autosomal recessive inheritance

Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the BLOC1S6 gene.

967
(38.1%)

Noonan syndrome 4

Cryptorchidism Keratosis pilaris Prolonged bleeding time Ventricular septal defect

Autosomal dominant inheritance

Any Noonan syndrome in which the cause of the disease is a mutation in the SOS1 gene.

968
(38.0%)

inflammatory bowel disease 28

Hematochezia Pyoderma

Autosomal recessive inheritance

Any inflammatory bowel disease in which the cause of the disease is a mutation in the IL10RA gene.

968
(38.0%)

intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency

Eczema Feeding difficulties Hodgkin lymphoma Hypospadias

Autosomal recessive inheritance

970
(37.8%)

dyskeratosis congenita, autosomal dominant 6

Abnormality of the dentition Aplastic anemia Esophageal stenosis Nail dystrophy

Autosomal dominant inheritance Autosomal recessive inheritance

A dyskeratosis congenita that has material basis in an autosomal dominant mutation of ACD on chromosome 16q22.1.

970
(37.8%)

intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities

Eosinophilia Feeding difficulties Narrow mouth Thin eyebrow

Autosomal dominant inheritance

972
(37.6%)

combined inflammatory and immunologic defect

Abnormality of the lymph nodes Growth abnormality Neutropenia Reduced delayed hypersensitivity

972
(37.6%)

short-limb skeletal dysplasia with severe combined immunodeficiency

Abnormal thorax morphology Agammaglobulinemia Hypoplasia of the thymus Lymphopenia

Autosomal recessive inheritance

Short-limb skeletal dysplasia with severe combined immunodeficiency is an extremely rare type of SCID characterized by the classical signs of T-B- SCID (severe and recurrent infections, diarrhea, failure to thrive, absence of T and B lymphocytes), associated with skeletal anomalies like short stature, bowing of the long bones and metaphyseal abnormalities of variable degree of severity.

972
(37.6%)

reticular dysgenesis

Hypoplasia of the thymus Lack of T cell function Lymphopenia

Autosomal recessive inheritance

Reticular dysgenesis is the most severe form of severe combined immunodeficiency (SCID) and is characterized by bilateral sensorineural deafness and a lack of innate and adaptive immune functions leading to fatal septicemia within days after birth if not treated.

972
(37.6%)

hyper-IgM syndrome type 3

Absence of lymph node germinal center Decreased circulating IgA level Neutropenia

Autosomal recessive inheritance

A form of Hyper IgM syndrome characterized by mutations of the CD40 gene. In this type, Immature B cells cannot receive signal 2 from helper T cells which is necessary to mature into mature B cells.

972
(37.6%)

lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome

Abnormality of the thymus Decreased circulating IgA level Decreased proportion of CD4-positive helper T cells Gonadal dysgenesis

Autosomal recessive inheritance

Lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome is characterised by immune deficiency, gonadal dysgenesis and fatal lung fibrosis. So far, it has been described in two sisters born to consanguineous parents. Both karyotypes were normal female (46,XX). No genetic anomalies could be identified by comparative genome hybridization analysis of their genomes or by analysis of genes known to be associated with these types of anomalies.

977
(37.6%)

Parana hard-skin syndrome

Abnormal abdomen morphology Abnormality of the skin

Autosomal recessive inheritance

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.

978
(37.6%)

immunoglobulin A deficiency 2

Abnormal lymphocyte morphology Decreased circulating IgA level Recurrent infection of the gastrointestinal tract

Any selective IgA deficiency disease in which the cause of the disease is a mutation in the TNFRSF13B gene.

978
(37.6%)

Pelger-Huet-like anomaly and episodic fever with abdominal pain

Abdominal pain Abnormality of blood and blood-forming tissues Fever

Autosomal recessive inheritance

978
(37.6%)

immunodeficiency 18

Defective T cell proliferation Lymphopenia Recurrent gastroenteritis

Autosomal recessive inheritance

Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18.

978
(37.6%)

primary intraosseous venous malformation

Elevated alkaline phosphatase Gingival bleeding Umbilical hernia

Autosomal recessive inheritance

Primary intraosseous venous malformation is a rare, genetic vascular anomaly characterized by severe blood vessel expansion (most frequently within the craniofacial bones) with painless bone enlargement (usually of mandibule, maxilla and/or orbital, nasal, and frontal bones), typically resulting in facial asymmetry and contour deformation. Midline abnormalities, such as diastasis recti, supraumbilical raphe, and hiatus hernia, are commonly associated. Additional features reported include gingival bleeding, ectopic tooth eruption, exophthalmos, loss of vision, nausea, and vomiting.

978
(37.6%)

agammaglobulinemia 3, autosomal recessive

Agammaglobulinemia Diarrhea Neutropenia

Autosomal recessive inheritance

Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the CD79A gene.

978
(37.6%)

agammaglobulinemia 4, autosomal recessive

Agammaglobulinemia Diarrhea Neutropenia

Autosomal recessive inheritance

Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the BLNK gene.

978
(37.6%)

enteropathy, familial, with villous edema and immunoglobulin G2 deficiency

Edema Neutropenia Vomiting

Autosomal dominant inheritance

978
(37.6%)

Wolfram syndrome 2

Abnormal bleeding Diabetes mellitus Gastric ulcer

Autosomal recessive inheritance

Any Wolfram syndrome in which the cause of the disease is a mutation in the CISD2 gene.

978
(37.6%)

action myoclonus-renal failure syndrome

Dysphagia Proteinuria Thrombocytopenia

Autosomal recessive inheritance

Action myoclonus-renal failure syndrome (AMRF) is a rare epilepsy syndrome characterized by progressive myoclonus epilepsy in association with primary glomerular disease. Patients present with neurologic symptoms (including tremor, action myoclonus, tonic-clonic seizures, later ataxia and dysarthria) that may precede, occur simultaneously or be followed by renal manifestations including proteinuria that progresses to nephrotic syndrome and end-stage renal disease. In some patients, sensorimotor peripheral neuropathy, sensorineural hearing loss and dilated cardiomyopathy are associated symptoms.

978
(37.6%)

3-methylglutaconic aciduria type 8

Increased serum lactate Neutropenia Poor suck

Autosomal recessive inheritance

978
(37.6%)

Krabbe disease

Autoimmune thrombocytopenia Recurrent fever Vomiting

Autosomal recessive inheritance

Krabbe disease is a lysosomal disorder that affects the white matter of the central and peripheral nervous systems. It includes infantile, late-infantile/juvenile and adult forms.

978
(37.6%)

immunodeficiency-centromeric instability-facial anomalies syndrome 1

Decreased circulating IgA level Diarrhea T lymphocytopenia

Autosomal recessive inheritance

Any immunodeficiency-centromeric instability-facial anomalies syndrome in which the cause of the disease is a mutation in the DNMT3B gene.

978
(37.6%)

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Abnormality of the coagulation cascade Feeding difficulties Hypoglycemia

Autosomal recessive inheritance

Any 3-methylglutaconic aciduria in which the cause of the disease is a mutation in the SERAC1 gene.

978
(37.6%)

Bartter disease type 2

Impaired platelet aggregation Renal salt wasting Vomiting

Autosomal recessive inheritance Heterogeneous

Any Bartter syndrome in which the cause of the disease is a mutation in the KCNJ1 gene.

978
(37.6%)

mosaic variegated aneuploidy syndrome 1

Feeding difficulties in infancy Leukemia Premature chromatid separation

Autosomal recessive inheritance

Any mosaic variegated aneuploidy syndrome in which the cause of the disease is a mutation in the BUB1B gene.

993
(37.5%)

peripheral motor neuropathy-dysautonomia syndrome

Achalasia Cyanosis Decreased nerve conduction velocity

Autosomal recessive inheritance

Peripheral motor neuropathy-dysautonomia syndrome is characterised by distal, slowly progressive muscular weakness, childhood-onset amyotrophy, autonomic dysfunction characterized by profuse sweating, distal cyanosis related to cold weather, orthostatic hypotension, and esophageal achalasia. It has been described in two sisters. Inheritance appears to be autosomal recessive.

993
(37.5%)

Chiari malformation type II

Cyanosis Dysphagia Hydrocephalus

Multifactorial inheritance

Arnold-Chiari malformation type II is a rare, central nervous system malformation characterized by caudal displacement of the cerebellum, pons, medulla and fourth ventricle through the foramen magnum into the spinal canal, and is typically associated with myelomeningocele. Variable other central nervous system abnormalities might be present (partial or complete agenesis of the corpus callosum, a small fourth ventricle, obstructive hydrocephalus, falx and tentorium defects, and polygyria). Symptoms include hypotonia, apnea with cyanosis, dysphagia, opisthotonus, nystagmus, spasticity, ataxia, and occipital headache.

995
(37.5%)

diabetes mellitus, transient neonatal, 3

Elevated hemoglobin A1c Hyperglycemia

Autosomal dominant inheritance

Any transient neonatal diabetes mellitus in which the cause of the disease is a mutation in the KCNJ11 gene.

996
(37.3%)

cholangiocarcinoma, susceptibility to

Cholangiocarcinoma

996
(37.3%)

cholelithiasis

Cholelithiasis

Polygenic inheritance

The presence of calculi in the gallbladder.

996
(37.3%)

primary biliary cholangitis 1

Biliary cirrhosis

Autosomal dominant inheritance

996
(37.3%)

fibrosclerosis, multifocal

Abnormality of the liver Abnormality of the neck Sclerosing cholangitis

Autosomal recessive inheritance

996
(37.3%)

Meckel syndrome, type 3

Bile duct proliferation Hepatic fibrosis Multicystic kidney dysplasia

Autosomal recessive inheritance

Any Meckel syndrome in which the cause of the disease is a mutation in the TMEM67 gene.