798
(42.2%)

Lambert syndrome

Inguinal hernia Jaundice

Autosomal recessive inheritance

Lambert syndrome is a very rare syndrome described in four sibs of one French family and characterized by branchial dysplasia (malar hypoplasia, macrostomia, preauricular tags and meatal atresia), club feet, inguinal herniae and cholestasis due to paucity of interlobular bile ducts and intellectual deficit.

798
(42.2%)

cholestasis with gallstone, ataxia, and visual disturbance

Jaundice Retinal degeneration

Autosomal recessive inheritance

798
(42.2%)

dysmyelination with jaundice

Cryptorchidism Jaundice

Autosomal recessive inheritance

798
(42.2%)

peroxisome biogenesis disorder 10b

Neurogenic bladder Prolonged neonatal jaundice

Autosomal recessive inheritance

798
(42.2%)

pituitary hormone deficiency, combined, 1

Jaundice Macroglossia

Autosomal dominant inheritance Autosomal recessive inheritance

Any combined pituitary hormone deficiencies, genetic form in which the cause of the disease is a mutation in the POU1F1 gene.

798
(42.2%)

microcephalic osteodysplastic primordial dwarfism type I

Cryptorchidism Prolonged neonatal jaundice

Autosomal recessive inheritance

A microcephalic osteodysplastic primordial dwarfism that has material basis in homozygous or compound heterozygous mutation in the RNU4ATAC gene, encoding a small nuclear RNA (snRNA) component of the U12-dependent (minor) spliceosome, on chromosome 2q14.2. It is characterized by dwarfism, microcephaly, and neurologic abnormalities, including mental retardation, brain malformations, and ocular, auditory sensory deficits.

807
(42.1%)

cleft lip/palate-intestinal malrotation-cardiopathy syndrome

Abnormality of the tongue Pancreatic islet-cell hyperplasia Visceromegaly

Autosomal recessive inheritance

Cleft lip/palate - intestinal malrotation - cardiopathy is a multiple congenital anomaly syndrome described in 5 patients to date, characterized by flat face, hypertelorism, flat occiput, upward slanting palpebral fissures, cleft palate, micrognathia, short neck, and severe congenital heart defects which were lethal in 3 of the 5 patients reported. Malrotation of the intestine, bilateral clinodactyly, bilobed tongue, short fourth metatarsals and bifid thumbs were reported in individual cases. There have been no further descriptions in the literature since 1997.

808
(42.0%)

Finnish type amyloidosis

Abnormal abdomen morphology Cutis laxa Generalized amyloid deposition Renal insufficiency

Autosomal dominant inheritance

808
(42.0%)

thyrotoxicosis

Abnormal abdomen morphology Abnormality of metabolism/homeostasis Pretibial myxedema Proptosis

A hypermetabolic syndrome caused by the elevation of thyroid hormone levels in the serum. Signs and symptoms include tachycardia, palpitations, tremor, weight loss, warm weather intolerance, and moist skin. Causes include Graves disease, toxic nodular goiter, toxic thyroid nodule, and lymphocytic thyroiditis.

808
(42.0%)

hypotonia with lactic acidemia and hyperammonemia

Abnormal renal tubule morphology Ascites Edema Redundant neck skin

Autosomal recessive inheritance

This syndrome is characterised by severe hypotonia, lactic academia and congenital hyperammonaemia.

811
(42.0%)

spastic paraplegia and Evans syndrome

Autoimmune thrombocytopenia Coombs-positive hemolytic anemia Spastic paraplegia

Autosomal recessive inheritance

811
(42.0%)

pancytopenia-developmental delay syndrome

Anemia Leukopenia Microcephaly

Autosomal recessive inheritance

811
(42.0%)

eosinophilia, familial

Anemia Eosinophilia Thrombocytopenia

Autosomal dominant inheritance

Familial occurrence, with more than one generation being affected, of persistent eosinophilia, an increase in the number of eosinophils in the blood, in the absence of known causal factors.

811
(42.0%)

ghosal hematodiaphyseal dysplasia

Leukopenia Refractory anemia Thrombocytopenia

Autosomal recessive inheritance

Ghosal hematodiaphyseal dysplasia syndrome (GHDD) is a rare disorder characterized by increased bone density (predominantly diaphyseal) and aregenerative corticosteroid-sensitive anemia.

811
(42.0%)

Diamond-Blackfan anemia 4

Atrial septal defect Macrocytic anemia Neutropenia Reticulocytopenia

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS17 gene.

811
(42.0%)

Diamond-Blackfan anemia 8

Macrocytic anemia Neutropenia Thick upper lip vermilion

Autosomal dominant inheritance

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

811
(42.0%)

Diamond-Blackfan anemia 5

Hypospadias Leukopenia Macrocytic anemia Reticulocytopenia

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL35A gene.

811
(42.0%)

radioulnar synostosis with amegakaryocytic thrombocytopenia 2

Anemia Hydrocele testis Neutropenia

Autosomal dominant inheritance

Any radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome in which the cause of the disease is a mutation in the MECOM gene.

811
(42.0%)

Diamond-Blackfan anemia 11

Anemia Neutropenia Renal agenesis

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL26 gene.

811
(42.0%)

ataxia-pancytopenia syndrome

Acute myelomonocytic leukemia Hypoplastic anemia Nystagmus

Autosomal dominant inheritance

Ataxia-pancytopenia syndrome is a rare genetic disease characterized by cerebellar ataxia, cytopenias and predisposition to bone marrow failure and myeloid leukaemia. 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.

821
(42.0%)

Diamond-Blackfan anemia 16

Anemia Atrial septal defect

Autosomal dominant inheritance

821
(42.0%)

pulmonary hemosiderosis

Iron deficiency anemia Recurrent intrapulmonary hemorrhage

Autosomal dominant inheritance Autosomal recessive inheritance

Idiopathic pulmonary hemosiderosis is a respiratory disease due to repeated episodes of diffuse alveolar hemorrhage without any underlying apparent cause, most often in children. Anemia, cough, and pulmonary infiltrates on chest radiographs are found in majority of the patients.

823
(42.0%)

neutrophil immunodeficiency syndrome

Impaired oxidative burst Poor wound healing Rectal abscess

Autosomal dominant inheritance

Neutrophil immunodeficiency syndrome is a primary immunodeficiency characterized by neutrophilia with severe neutrophil dysfunction, leukocytosis, a predisposition to bacterial infections and poor wound healing, including an absence of pus in infected areas.

823
(42.0%)

leukocyte adhesion deficiency 1

Gingivitis Leukocytosis Poor wound healing Rectal abscess

Autosomal recessive inheritance

Leukocyte adhesion deficiency type I (LAD-I) is a form of LAD characterized by life-threatening, recurrent bacterial infections.

823
(42.0%)

dyskeratosis congenita, autosomal dominant 2

Abnormality of the dentition Chronic diarrhea Premature graying of hair Thrombocytopenia

Autosomal dominant inheritance Autosomal recessive inheritance Genetic anticipation

A dyskeratosis congenita that has material basis in an autosomal dominant mutation of TERT on chromosome 5p15.33.

826
(41.8%)

autosomal recessive cutis laxa type 2A

Abnormal isoelectric focusing of serum transferrin Cutis laxa Inguinal hernia

Autosomal recessive inheritance

An autosomal recessive cutis laxa type II classic type that has material basis in homozygous or compound heterozygous mutations in the ATP6V0A2 gene on chromosome 12q24.

827
(41.6%)

Fanconi anemia complementation group D1

Acute myeloid leukemia Anal atresia Cafe-au-lait spot Chromosomal breakage induced by crosslinking agents

Autosomal recessive inheritance

Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations is a rare cancer-predisposing syndrome, associated with the D1 subgroup of Fanconi anemia (FA), characterized by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies. Bone marrow suppression and the incidence of developmental abnormalities are less frequent than in other FA, but cancer risk is very high with the spectrum of childhood cancers including Wilms tumor, brain tumor (often medulloblastoma) and ALL/AML.

827
(41.6%)

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Cafe-au-lait spot Hypoglycemia Thrombocytopenia Umbilical hernia

Autosomal dominant inheritance

827
(41.6%)

Dubowitz syndrome

Aplastic anemia Decreased circulating IgA level Inguinal hernia Sacral dimple

Autosomal recessive inheritance

Dubowitz syndrome (DS) is a rare multiple congenital syndrome characterized primarly by growth retardation, microcephaly, distinctive facial dysmorphism, cutaneous eczema, a mild to severe intellectual deficit and genital abnormalities.

830
(41.3%)

neonatal acute respiratory distress due to SP-B deficiency

Abnormality of metabolism/homeostasis Cyanosis Pulmonary arterial hypertension

Autosomal recessive inheritance Heterogeneous

830
(41.3%)

primary hyperoxaluria type 1

Acrocyanosis Cutis marmorata Hematuria Renal insufficiency

Autosomal recessive inheritance

Primary hyperoxaluria type 1 (PH1) is a rare disorder of glyoxylate metabolism characterized by the accumulation of oxalate due to a deficiency of the peroxisomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). Clinical presentation is variable, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement.

832
(41.2%)

hypercholanemia, familial 1

Low levels of vitamin K Pruritus Steatorrhea

Autosomal recessive inheritance

A very rare genetic disorder characterized clinically by elevated serum bile acid concentrations, itching, and fat malabsorption reported in patients of Old Order Amish descent.

833
(41.1%)

Tn polyagglutination syndrome

Abnormal erythrocyte morphology Autoimmunity

Somatic mutation

833
(41.1%)

Monosomy 7 myelodysplasia and leukemia syndrome 1

Acute myeloid leukemia Increased mean corpuscular volume Thrombocytopenia

Autosomal dominant inheritance Autosomal recessive inheritance

835
(41.1%)

Muckle-Wells syndrome

Abnormality of the skin Conjunctivitis Leukocytosis Renal amyloidosis

Autosomal dominant inheritance

Muckle-Wells syndrome (MWS) is an intermediate form of cryopyrin-associated periodic syndrome (CAPS) and is characterized by recurrent fever (with malaise and chills), recurrent urticaria-like skin rash, sensorineural deafness, general signs of inflammation (eye redness, headaches, arthralgia/myalgia) and potentially life-threatening secondary amyloidosis (AA type).

835
(41.1%)

hereditary mucoepithelial dysplasia

Chronic mucocutaneous candidiasis Eosinophilia Hematuria Keratoconjunctivitis

Autosomal dominant inheritance

Hereditary mucoepithelial dysplasia (HMD) is a condition that affects the skin, hair, mucosa (areas ofthe body that are lined with mucus), gums (gingiva), eyes, nose and lungs. Symptoms typically begin in infancy and may include development of cataracts (clouding of the eye lens); blindness; hair loss (alopecia); abnormal changes to the perineum (the area between the anus and external genitalia); and small, skin-colored bumps (keratosis pilaris). Terminal lung disease has also been reported. The cause of HMD is thought to be an abnormality in desmosomes and gap junctions, which are structures involved in cell-to-cell contact. HMD typically follows autosomal dominant inheritance, but has occurred sporadically (in an individual who has no family history of the condition). Treatment typically focuses on individual symptoms of the condition.

837
(41.0%)

laterality defects, autosomal dominant

Asplenia Growth abnormality

Autosomal dominant inheritance

837
(41.0%)

heterotaxy, visceral, 4, autosomal

Ectopia of the spleen Ventricular septal defect

Autosomal dominant inheritance

Any visceral heterotaxy in which the cause of the disease is a mutation in the ACVR2B gene.

837
(41.0%)

heterotaxy, visceral, 2, autosomal

Polysplenia Transposition of the great arteries

Autosomal dominant inheritance

837
(41.0%)

primary ciliary dyskinesia 14

Otitis media Polysplenia

Autosomal recessive inheritance

Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the CCDC39 gene.

837
(41.0%)

holoprosencephaly 11

Cleft palate Polysplenia

Autosomal dominant inheritance Sporadic

Any holoprosencephaly in which the cause of the disease is a mutation in the CDON gene.

837
(41.0%)

isolated congenital hypoglossia/aglossia

Asplenia Narrow mouth

Sporadic

Isolated aglossia and hypoglossia are terms covering the spectrum from partial to total absence of the tongue. These congenital malformations have been classified as part of the group of oromandibular-limb hypogenesis syndromes (OLHS).

837
(41.0%)

right atrial isomerism (disease)

Asplenia Inguinal hernia

Autosomal recessive inheritance

A visceral heterotaxy characterized by complete atrioventricular septal defect with a common atrium and univentricular AV connection, total anomalous pulmonary drainage, and transposition or malposition of the great arteries and may be associated with bilateral trilobed lungs, midline liver, asplenia and situs inversus affecting other organs that has material basis in homozygous mutation in the GDF1 gene on chromosome 19p12.

837
(41.0%)

heterotaxy, visceral, 7, autosomal

Atrial septal defect Polysplenia

Autosomal recessive inheritance

Any visceral heterotaxy in which the cause of the disease is a mutation in the MMP21 gene.

837
(41.0%)

primary ciliary dyskinesia 1

Asplenia Sinusitis

Autosomal recessive inheritance Heterogeneous

Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the DNAI1 gene.

837
(41.0%)

tetraamelia syndrome 1

Absent external genitalia Asplenia

Autosomal recessive inheritance Heterogeneous

837
(41.0%)

heterotaxy, visceral, 1, X-linked

Asplenia Horseshoe kidney

X-linked recessive inheritance

X-linked visceral heterotaxy type 1 is a very rare form of heterotaxy that has only been reported in a few families. Heterotaxy is the right/left transposition of thoracic and/or abdominal organs. This condition is caused by mutations in the ZIC3 gene, is inherited in an X-linked recessive fashion, and is usually seen in males. Physical features include heart abnormalities such as dextrocardia, transposition of great vessels, ventricular septal defect, patent ductus arteriosus, pulmonic stenosis ; situs inversus, and missing (asplenia) and/or extra spleens (polysplenia).Affected individualscan also experience abnormalities in the development of the midline of the body, which can cause holoprosencephaly, myelomeningocele, urological anomalies, widely spaced eyes (hypertelorism), cleft palate, and abnormalities of the sacral spine and anus. Heterotaxia with recurrent respiratory infections are called primary ciliary dyskinesia.

837
(41.0%)

Sweeney-Cox syndrome

Asplenia Narrow mouth

Autosomal dominant inheritance

837
(41.0%)

Feingold syndrome type 1

Annular pancreas Asplenia High palate

Autosomal dominant inheritance

Feingold syndrome type 1 (FS1) is a rare inherited malformation syndrome characterized by microcephaly, short stature and numerous digital anomalies.

837
(41.0%)

Matthew-Wood syndrome

Hypoplasia of the uterus Hypoplastic spleen

Autosomal recessive inheritance

Matthew-Wood syndrome is a rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia.

837
(41.0%)

hydrolethalus syndrome 1

Accessory spleen Hypospadias

Autosomal recessive inheritance

Any hydrolethalus syndrome in which the cause of the disease is a mutation in the HYLS1 gene.

852
(41.0%)

Jacobsen syndrome

Annular pancreas Cryptorchidism Thrombocytopenia

Sporadic

Jacobsen syndrome is a multiple congenital anomaly/mental retardation (MCA/MR) contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11.

853
(40.9%)

congenital neuronal ceroid lipofuscinosis

Abnormality of the spleen Hepatic failure

Autosomal recessive inheritance

Congenital neuronal ceroid lipofuscinosis (CNCL) is a severe form of neuronal ceroid lipofuscinosis (NCL) with onset at birth characterized by primary microcephaly, neonatal epilepsy, and death in early infancy.

853
(40.9%)

Tuftsin deficiency

Abnormality of the spleen

Autosomal dominant inheritance

855
(40.8%)

hepatic veno-occlusive disease-immunodeficiency syndrome

Abnormality of the liver Absence of lymph node germinal center Decreased circulating IgG level Microcephaly

Autosomal recessive inheritance

Hepatic veno-occlusive disease-immunodeficiency syndrome is characterized by the association of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease.

855
(40.8%)

Bruton-type agammaglobulinemia

Agammaglobulinemia Enteroviral hepatitis Lymph node hypoplasia Recurrent urinary tract infections

X-linked recessive inheritance

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.

857
(40.8%)

Noonan syndrome 1

Abnormal bleeding Low posterior hairline Lymphedema Patent ductus arteriosus

Autosomal dominant inheritance

Noonan syndrome caused by mutations in the PTPN11 gene.

858
(40.7%)

Hennekam lymphangiectasia-lymphedema syndrome 1

Bilateral single transverse palmar creases Cryptorchidism Intestinal lymphangiectasia Lymphedema

Autosomal recessive inheritance

Any Hennekam syndrome in which the cause of the disease is a mutation in the CCBE1 gene.

858
(40.7%)

Costello syndrome

Hyperpigmentation of the skin Hypoglycemia Lymphangiectasis Renal insufficiency

Autosomal dominant inheritance Sporadic

Costello syndrome (CS) is a rare multisystemic disorder characterized by failure to thrive, short stature, developmental delay or intellectual disability, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors.

860
(40.7%)

DK1-CDG

Abnormal isoelectric focusing of serum transferrin Dilated cardiomyopathy Ichthyosis Sparse and thin eyebrow

Autosomal recessive inheritance

DK1-CDG is characterised by muscular hypotonia and ichthyosis. It has been described in four children from two consanguineous families. All the affected children died during early infancy, two from dilated cardiomyopathy. The syndrome is caused by a deficiency in dolichol kinase 1 (DK1), an enzyme involved in the de novo biosynthesis of dolichol phosphate. The mutations identified in the DK1 gene led to a 96 to 98% reduction in DK activity.

861
(40.7%)

cranioectodermal dysplasia 4

Bone marrow hypocellularity Ectodermal dysplasia Nephropathy Recurrent pneumonia

Autosomal recessive inheritance

861
(40.7%)

dyskeratosis congenita, autosomal dominant 3

Cryptorchidism Leukopenia Premature graying of hair Thrombocytopenia

Autosomal dominant inheritance

A dyskeratosis congenita that has material basis in an autosomal dominant mutation of TINF2 on chromosome 14q12.

863
(40.7%)

nephropathy, progressive tubulointerstitial, with cholestatic liver disease

Cholestatic liver disease Nephropathy

Autosomal recessive inheritance

863
(40.7%)

cholestasis, progressive familial intrahepatic, 4

Hepatic failure Hepatocellular carcinoma Intrahepatic cholestasis

Autosomal recessive inheritance

Any progressive familial intrahepatic cholestasis in which the cause of the disease is a mutation in the TJP2 gene.

863
(40.7%)

nephronophthisis 18

Cholestasis Nephronophthisis

Autosomal recessive inheritance

Any nephronophthisis in which the cause of the disease is a mutation in the CEP83 gene.

863
(40.7%)

nephronophthisis 16

Cholestasis Hepatic fibrosis Renal insufficiency

Autosomal recessive inheritance

Any nephronophthisis in which the cause of the disease is a mutation in the ANKS6 gene.

863
(40.7%)

Senior-Loken syndrome 9

Cholestasis Hepatic fibrosis Nephronophthisis

Autosomal recessive inheritance

Any Senior-Loken syndrome in which the cause of the disease is a mutation in the TRAF3IP1 gene.

863
(40.7%)

MEDNIK syndrome

Cholestasis Cirrhosis High forehead

Autosomal recessive inheritance

MEDNIK syndrome, previously known as Erythrokeratodermia Variabilis type 3 (EKV3), is characterized by intellectual deficit, enteropathy, sensorineural hearing loss, peripheral neuropathy, lamellar and erythrodermic ichthyosis, and keratodermia (MEDNIK stands for Mental retardation, Enteropathy, Deafness, peripheral Neuropathy, Ichtyosis, Keratodermia).

869
(40.4%)

ALG3-CDG

Bifid uvula Small nail Type I transferrin isoform profile Vomiting

Autosomal recessive inheritance

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).

870
(40.3%)

body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency

Atherosclerosis Cutis laxa Epistaxis

Autosomal recessive inheritance

Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency is a very rare genetic skin disease characterized by severe skin laxity affecting the trunk and limbs.

870
(40.3%)

osteogenesis imperfecta type 17

Delayed speech and language development Intraventricular hemorrhage Soft skin

Autosomal recessive inheritance

Any osteogenesis imperfecta in which the cause of the disease is a mutation in the SPARC gene.

870
(40.3%)

immunodeficiency 49

Cutis laxa Eosinophilia Hypertelorism Pulmonary artery stenosis

Autosomal dominant inheritance

Any primary immunodeficiency disease in which the cause of the disease is a mutation in the BCL11B gene.

870
(40.3%)

CHIME syndrome

Acute lymphoblastic leukemia Palmoplantar hyperkeratosis Tetralogy of Fallot Ureteropelvic junction obstruction

Autosomal recessive inheritance

CHIME syndrome is a rare ectodermal dysplasia syndrome characterized by ocular colobomas, cardiac defects, ichthyosiform dermatosis, intellectual disability, conductive hearing loss and epilepsy.

870
(40.3%)

Rubinstein-Taybi syndrome due to CREBBP mutations

Cryptorchidism Leukemia Patent ductus arteriosus Single transverse palmar crease

Autosomal dominant inheritance Heterogeneous Sporadic

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

875
(40.2%)

primary immunodeficiency syndrome due to p14 deficiency

Decreased circulating total IgM Hypopigmentation of the skin Neutropenia

Autosomal recessive inheritance

Primary immunodeficiency syndrome due to p14 deficiency is characterised by short stature, hypopigmentation, coarse facies and frequent bronchopulmonary Streptococcus pneumoniae infections.

875
(40.2%)

Griscelli syndrome type 2

Accumulation of melanosomes in melanocytes Hemophagocytosis Recurrent bacterial infections Reduced delayed hypersensitivity

Autosomal recessive inheritance

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.

875
(40.2%)

X-linked Alport syndrome

Ichthyosis Nephritis Proteinuria Thrombocytopenia

X-linked inheritance X-linked dominant inheritance Heterogeneous

X-linked form of Alport syndrome.

875
(40.2%)

Lichtenstein syndrome

Decreased circulating IgA level Neutropenia Single transverse palmar crease

Autosomal recessive inheritance

Lichstenstein syndrome is characterised by frequent infections associated with osteoporosis, a tendency for fractures and osseous anomalies. It has been described in two monozygotic twin brothers. Transmission is autosomal recessive.

875
(40.2%)

nephrotic syndrome 14

Ichthyosis Lymphopenia Proteinuria

Autosomal recessive inheritance

875
(40.2%)

Noonan syndrome 6

Cafe-au-lait spot Edema Juvenile myelomonocytic leukemia

Autosomal dominant inheritance

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

875
(40.2%)

Fanconi anemia complementation group I

Cafe-au-lait spot Chromosomal breakage induced by crosslinking agents Neutropenia

Autosomal recessive inheritance

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

875
(40.2%)

CBL-related disorder

Cafe-au-lait spot Juvenile myelomonocytic leukemia Lymphedema

Autosomal dominant inheritance

CBL-related disorder is a genetic condition caused by pathogenic variants in the Cbl ubiquitin ligase gene, (CBL; HGNC:1541). Due to the proposed mechanism indicating the CBL gene's relationship to the RAS-MAPK pathway and the phenotypic presentation similar to that of the RASopathies, CBL-related disorder should be considered a RASopathy disorder. Though there is a wide spectrum of phenotypic variability, broadly, patients with CBL-related disorder have presented with developmental delay, intellectual disability, neurodevelopmental alterations, prenatal lymphatic anomalies, cardiac malformations as well as vascular anomalies particularly affecting the brain (e.g. Moya-moya arteriopathies), craniofacial features indicative of a RASopathy, hypotonia, feeding difficulties, edema of the legs, musculoskeletal and respiratory thorax abnormalities, ectodermal features including cafe-au-lait spots, immunological and hematological disorders and susceptibility to tumors diagnosed as juvenile myelomonocytic leukemia (JMML) that is usually self-remitting. Note tumor risk beyond JMML has not yet been thoroughly assessed. Due to the clinical presentation of a broad spectrum of these and other phenotypes in patients with variants in CBL, these conditions are currently defined by experts in reference to the causal gene, CBL.

883
(40.2%)

Fanconi anemia complementation group N

Aplastic anemia Cafe-au-lait spot Chromosomal breakage induced by crosslinking agents Ventricular septal defect

Autosomal recessive inheritance

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

884
(40.2%)

holocarboxylase synthetase deficiency

Metabolic acidosis Skin rash Thrombocytopenia Vomiting

Autosomal recessive inheritance

Holocarboxylase synthetase (HCS) deficiency is a life-threatening early-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism, that, if untreated, is characterized by vomiting, tachypnea, irritability, lethargy, exfoliative dermatitis, and seizures that can worsen to coma.

884
(40.2%)

NAD(P)HX dehydratase deficiency

Cerebral edema Pancytopenia Skin rash Vomiting

Autosomal recessive inheritance

884
(40.2%)

granulocytopenia with immunoglobulin abnormality

Decreased circulating antibody level Diarrhea Granulocytopenia Recurrent skin infections

Autosomal recessive inheritance

884
(40.2%)

leukoencephalopathy, arthritis, colitis, and hypogammaglobulinema

Diarrhea Eczema Elevated erythrocyte sedimentation rate Neutropenia

Autosomal recessive inheritance X-linked inheritance

884
(40.2%)

Pelger-Huet anomaly

Abnormality of chromosome segregation Eczema Thrombocytopenia Umbilical hernia

Autosomal dominant inheritance

An autosomal dominant inherited condition caused by mutations in the lamin B receptor gene. It is characterized by defects in the neutrophil lobulation, resulting in the presence of dumbbell-shaped neutrophils with bilobed nuclei in the peripheral blood smear.

889
(40.2%)

Addison disease

Adrenal hypoplasia Cyanosis Hypoglycemia Vomiting

Autosomal recessive inheritance

Addison disease (AD) is a chronic and rare endocrine disorder due to autoimmune destruction of the adrenal cortex and resulting in a glucocorticoid and mineralocorticoid deficiency. Properly speaking AD designates autoimmune adrenalitis, but it is a term commonly used to describe any form of chronic primary adrenal insufficiency (CPAI).

889
(40.2%)

Riley-Day syndrome

Acrocyanosis Glomerular sclerosis Recurrent fever Vomiting

Autosomal recessive inheritance

A congenital disorder caused by mutations in the IKBKAP gene. It is characterized by damage of the sympathetic and parasympathetic and sensory nervous system.

891
(40.0%)

immune deficiency disease

Cholangitis Decreased circulating total IgM Fulminant hepatitis Recurrent bacterial infections

Autosomal recessive inheritance

891
(40.0%)

cystic fibrosis

Biliary cirrhosis Dehydration Exocrine pancreatic insufficiency Failure to thrive

Autosomal recessive inheritance

Cystic fibrosis (CF) is a genetic disorder characterized by the production of sweat with a high salt content and mucus secretions with an abnormal viscosity.

891
(40.0%)

psoriasis 14, pustular

Cholangitis Fever Furrowed tongue

Autosomal recessive inheritance

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

891
(40.0%)

cerebrotendinous xanthomatosis

Abnormal circulating cholesterol concentration Cataract Cholelithiasis

Autosomal recessive inheritance

Cerebrotendinous xanthomatosis (CTX) is an anomaly of bile acid synthesis characterized by neonatal cholestasis, childhood-onset cataract, adolescent to young adult-onset tendon xanthomata, and brain xanthomata with adult-onset neurologic dysfunction.

891
(40.0%)

renal cysts and diabetes syndrome

Biliary tract abnormality Hypoplasia of the uterus Proteinuria

Autosomal dominant inheritance

Renal cysts and diabetes syndrome (RCAD) is a rare form of maturity-onset diabetes of the young (MODY) characterized clinically by heterogeneous cystic renal disease and early-onset familial non-autoimmune diabetes. Pancreatic atrophy, liver dysfunction and genital tract anomalies are also features of the syndrome.

891
(40.0%)

peroxisome biogenesis disorder 12A (Zellweger)

Cholelithiasis Hyperbilirubinemia Renal tubular dysfunction

Autosomal recessive inheritance

891
(40.0%)

pancreatic hypoplasia-diabetes-congenital heart disease syndrome

Biliary atresia Diabetes mellitus Inguinal hernia Pancreatic hypoplasia

Autosomal dominant inheritance

Pancreatic hypoplasia-diabetes-congenital heart disease syndrome is characterized by partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis).

891
(40.0%)

X-linked intellectual disability-craniofacioskeletal syndrome

Absent gallbladder Cryptorchidism Hypocalcemia

X-linked recessive inheritance X-linked dominant inheritance

X-linked intellectual disability-craniofacioskeletal syndrome is a rare, hereditary, syndromic intellectual disability characterized by craniofacial and skeletal abnormalities in association with mild intellectual disability in females and early postnatal lethality in males. In addition to mild cognitive impairment, females present with microcephaly, short stature, skeletal features and extra temporal lobe gyrus. In males, intrauterine growth impairment, cardiac and urogenital anomalies have been reported.

891
(40.0%)

Bardet-Biedl syndrome 1

Biliary tract abnormality Diabetes mellitus Micropenis

Autosomal recessive inheritance

A Bardet-Biedl syndrome that has material basis in homozygous mutation in the BBS1 gene on chromosome 11q13.

900
(39.9%)

dyskeratosis congenita, autosomal recessive 5

Colitis Decreased circulating antibody level Leukopenia Nail dystrophy

Autosomal dominant inheritance Autosomal recessive inheritance

A dyskeratosis congenita that has material basis in an autosomal dominant mutation of RTEL1 on chromosome 20q13.33.