398
(49.9%)

transient infantile hypertriglyceridemia and hepatosteatosis

Hepatic fibrosis Hypertriglyceridemia Splenomegaly

Autosomal recessive inheritance

398
(49.9%)

combined immunodeficiency due to ZAP70 deficiency

Eczematoid dermatitis Hepatomegaly Panhypogammaglobulinemia Splenomegaly

Autosomal recessive inheritance

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.

398
(49.9%)

encephalopathy due to prosaposin deficiency

Abnormal glycosphingolipid metabolism Hepatomegaly Optic atrophy Splenomegaly

Autosomal recessive inheritance

Encephalopathy due to prosaposin deficiency is a lysosomal storage disease belonging to the group of sphingolipidoses.

398
(49.9%)

hemochromatosis type 2A

Azoospermia Cirrhosis Increased circulating ferritin concentration Splenomegaly

Autosomal recessive inheritance

Any hemochromatosis type 2 in which the cause of the disease is a mutation in the HJV gene.

398
(49.9%)

polycystic kidney disease 4

Dehydration Periportal fibrosis Renal insufficiency Splenomegaly

Autosomal recessive inheritance

A autosomal dominant polycystic kidney disease that has material basis in mutation in the PKD4 gene.

398
(49.9%)

acrodermatitis enteropathica

Hepatomegaly Hypogonadism Low alkaline phosphatase Splenomegaly

Autosomal recessive inheritance

Acrodermatitis enteropathica (AE) is a rare inherited inborn error of metabolism resulting in a severe zinc deficiency and characterized by acral dermatitis, alopecia, diarrhea and growth failure.

398
(49.9%)

Tangier disease

Decreased HDL cholesterol concentration Hepatomegaly Splenomegaly Visual impairment

Autosomal recessive inheritance

Tangier disease (TD) is a rare lipoprotein metabolism disorder characterized biochemically by an almost complete absence of plasma high-density lipoproteins (HDL), and clinically by liver, spleen, lymph node and tonsil enlargement along with peripheral neuropathy in children and adolescents, and, occasionally, cardiovascular disease in adults.

398
(49.9%)

glycogen storage disease II

Fever Hepatomegaly Macroglossia Splenomegaly

Autosomal recessive inheritance

Glycogen storage disease due to acid maltase deficiency (AMD) is an autosomal recessive trait leading to metabolic myopathy that affects cardiac and respiratory muscles in addition to skeletal muscle and other tissues. AMD represents a wide spectrum of clinical presentations caused by an accumulation of glycogen in lysosomes: Glycogen storage disease due to acid maltase deficiency, infantile onset, non-classic infantile onset and adult onset. Early onset forms are more severe and often fatal.

398
(49.9%)

Sanfilippo syndrome type A

Dense calvaria Heparan sulfate excretion in urine Hepatomegaly Splenomegaly

Autosomal recessive inheritance

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme heparan sulfate sulfatase. It is characterized by behavioral changes, sleep disturbances, mental developmental delays and seizures.

398
(49.9%)

sterile multifocal osteomyelitis with periostitis and pustulosis

Hepatomegaly Hyperkeratosis Joint swelling Splenomegaly

Autosomal recessive inheritance

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.

398
(49.9%)

Sanfilippo syndrome type B

Dense calvaria Heparan sulfate excretion in urine Hepatomegaly Splenomegaly

Autosomal recessive inheritance

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

398
(49.9%)

COG4-CDG

Cirrhosis Elevated alkaline phosphatase Microcephaly Splenomegaly

Autosomal recessive inheritance

COG4-CDG is an extremely rare form of CDG syndrome characterized clinically in the single reported case to date by seizures, some dysmorphic features, axial hyponia, slight peripheral hypertonia and hyperreflexia.

398
(49.9%)

biotinidase deficiency

Hepatomegaly Hyperammonemia Sensorineural hearing impairment Splenomegaly

Autosomal recessive inheritance

Biotinidase deficiency is a late-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism that, if untreated, is characterized by seizures, breathing difficulties, hypotonia, skin rash, alopecia, hearing loss and delayed development.

398
(49.9%)

sialuria

Abnormality of metabolism/homeostasis Hepatomegaly Inguinal hernia Splenomegaly

Autosomal dominant inheritance

Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.

398
(49.9%)

Sanfilippo syndrome type C

Everted lower lip vermilion Heparan sulfate excretion in urine Hepatomegaly Splenomegaly

Autosomal recessive inheritance

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.

398
(49.9%)

mucosulfatidosis

Hepatomegaly Hydrocephalus Mucopolysacchariduria Splenomegaly

Autosomal recessive inheritance

Multiple sulfatase deficiency (MSD) is a very rare and fatal lysosomal storage disease characterized by a clinical phenotype that combines the features of different sulfatase deficiencies (whether lysosomal or not) that can have neonatal (most severe), infantile (most common) and juvenile (rare) presentations with manifestations including hypotonia, coarse facial features, mild deafness, skeletal anomalies, ichthyosis, hepatomegaly, developmental delay, progressive neurologic deterioration and hydrocephalus.

398
(49.9%)

Sanfilippo syndrome type D

Heparan sulfate excretion in urine Hepatomegaly Splenomegaly Wide mouth

Autosomal recessive inheritance

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme N-acetylglucosamine-6-sulfatase. It is characterized by behavioral changes, sleep disturbances and mental developmental delays.

398
(49.9%)

congenital generalized lipodystrophy type 4

Hepatic steatosis Hyperinsulinemia Splenomegaly

Autosomal recessive inheritance

Any congenital generalized lipodystrophy in which the cause of the disease is a mutation in the CAVIN1 gene.

398
(49.9%)

mucopolysaccharidosis type 6

Dermatan sulfate excretion in urine Hepatomegaly Inguinal hernia Splenomegaly

Autosomal recessive inheritance

Mucopolysaccharidosis type 6 (MPS 6) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B (ASB) leading to the accumulation of dermatan sulfate.

398
(49.9%)

mullerian derivatives-lymphangiectasia-polydactyly syndrome

Hepatomegaly Inguinal hernia Lymphedema Splenomegaly

Autosomal recessive inheritance

Mullerian derivatives-lymphangiectasia-polydactyly syndrome is characterised by prenatal linear growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, postaxial polydactyly and cryptorchidism. Mullerian duct remnants, lymphangiectasis, and renal anomalies are also present. Three cases have been described. A small penis was observed in two of these cases. The syndrome is likely to be an autosomal recessive or X-linked trait. All the reported patients died neonatally of hepatic failure.

398
(49.9%)

mucopolysaccharidosis type 2

Heparan sulfate excretion in urine Hepatomegaly Inguinal hernia Splenomegaly

X-linked recessive inheritance

Mucopolysaccharidosis type 2 (MPS2) is a lysosomal storage disease leading to a massive accumulation of glycosaminoglycans and a wide variety of symptoms including distinctive coarse facial features, short stature, cardio-respiratory involvement and skeletal abnormalities. It manifests as a continuum varying from a severe to an attenuated form without neuronal involvement.

398
(49.9%)

mucopolysaccharidosis type 7

Hepatomegaly Hydrops fetalis Inguinal hernia Splenomegaly

Autosomal recessive inheritance

Mucopolysaccharidosis type VII (MPS VII) is a very rare lysosomal storage disease belonging to the group of mucopolysaccharidoses.

398
(49.9%)

Hurler syndrome

Hepatosplenomegaly Inguinal hernia Splenomegaly Urinary glycosaminoglycan excretion

Autosomal recessive inheritance

Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy.

398
(49.9%)

nephropathic cystinosis

Hepatomegaly Male hypogonadism Proteinuria Splenomegaly

Autosomal recessive inheritance

An autosomal recessive condition caused by mutation(s) in the CTNS gene, encoding cystinosin. It is a sub-type of cystinosis, in which accumulation of cystine in the kidney results in renal dysfunction.

398
(49.9%)

Beemer-Langer syndrome

Edema Inguinal hernia Periportal fibrosis Splenomegaly

Autosomal recessive inheritance

Short rib-polydactyly syndrome (SRPS), Beemer-Langer type is an extremely rare type of SRPS developing prenatally or immediately after birth and characterized by short and narrow thorax with horizontally oriented ribs. Other bone features include small iliac bones, short tubular bones, bowing of long bones and rarely pre- and post-axial polydactyly. Brain defects are common and some cases of cleft lip, absent internal genitalia and renal, biliary and pancreatic cysts have been reported. The course is rapidly fatal.

398
(49.9%)

mucolipidosis type II

Deficiency of N-acetylglucosamine-1-phosphotransferase Hepatomegaly Inguinal hernia Splenomegaly

Autosomal recessive inheritance

Mucolipidosis II (MLII) is a slowly progressive lysosomal disorder characterized by growth retardation, skeletal abnormalities, facial dysmorphism, stiff skin, developmental delay and cardiomegaly.

427
(49.8%)

hypervitaminosis a, susceptibility to

Abnormality of the coagulation cascade Abnormality of the liver Ascites Hypercalcemia

Autosomal recessive inheritance

428
(49.8%)

protoporphyria, erythropoietic, 2

Cutaneous photosensitivity Iron deficiency anemia

Autosomal dominant inheritance

429
(49.6%)

congenital disorder of glycosylation type 1C

Elevated serum transaminases during infections Reduced factor XI activity Type I transferrin isoform profile

Autosomal recessive inheritance

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).

429
(49.6%)

PGM1-CDG

Hepatic steatosis Reduced antithrombin III activity Type I transferrin isoform profile

Autosomal recessive inheritance

431
(49.5%)

galactosialidosis

Coarse facial features Conjunctival telangiectasia Hepatosplenomegaly Nonimmune hydrops fetalis

Autosomal recessive inheritance

Galactosialidosis is a lysosomal storage disease characterized by coarse facial features, macular ''cherry red spot'', and dysostosis multiplex. Clinical presentation can be heterogenous ranging from a severe, early-onset, rapidly progressive infantile form to late onset, slowly progressive juvenile/adult form.

431
(49.5%)

familial partial lipodystrophy, Kobberling type

Hepatomegaly Increased facial adipose tissue Insulin-resistant diabetes mellitus Prominent superficial veins

Autosomal dominant inheritance

Familial partial lipodystrophy, Kobberling type, is a very rare form of familial partial lipodystrophy (FPLD) of unknown etiology characterized by lipoatrophy that is confined to the limbs and a normal or increased fat distribution of the face, neck, and trunk. Arterial hypertension and diabetes have also been associated. Inheritance is thought to be autosomal dominant.

431
(49.5%)

glycogen storage disease due to glucose-6-phosphatase deficiency type IB

Hepatomegaly Proteinuria Renal insufficiency Spider hemangioma

Autosomal recessive inheritance

Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type b, or glycogen storage disease (GSD) type 1b, is a type of glycogenosis due to G6P deficiency.

431
(49.5%)

mandibular hypoplasia-deafness-progeroid syndrome

Cryptorchidism Diabetes mellitus Hepatomegaly Telangiectasia

Autosomal dominant inheritance

431
(49.5%)

familial partial lipodystrophy, Dunnigan type

Hepatomegaly Insulin-resistant diabetes mellitus Polycystic ovaries Prominent superficial veins

Autosomal dominant inheritance

Familial Partial lipodystrophy, Dunnigan type (FPLD2) is a rare form of genetic lipodystrophy characterized by a loss of subcutaneous adipose tissue from the trunk, buttocks and limbs; fat accumulation in the neck, face, axillary and pelvic regions; muscular hypertrophy; and usually associated with metabolic complications such as insulin resistance, diabetes mellitus, dyslipidemia and liver steatosis.

431
(49.5%)

gapo syndrome

Abnormality of metabolism/homeostasis Abnormality of the dentition Hepatomegaly Prominent scalp veins

Autosomal recessive inheritance

GAPO syndrome is a multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations

437
(49.4%)

ichthyosis and male hypogonadism

Abnormality of metabolism/homeostasis Congenital ichthyosiform erythroderma Hyperchromic macrocytic anemia Male hypogonadism

X-linked inheritance

437
(49.4%)

myopathy, lactic acidosis, and sideroblastic anemia 1

High palate Increased serum lactate Pallor Sideroblastic anemia

Autosomal recessive inheritance

Any myopathy, lactic acidosis, and sideroblastic anemia in which the cause of the disease is a mutation in the PUS1 gene.

439
(49.4%)

COG1-CDG

Abnormal isoelectric focusing of serum transferrin Anemia Cryptorchidism Recurrent infections

Autosomal recessive inheritance

COG1-CDG is an extremely rare form of CDG syndrome characterized clinically in the few cases reported to date by variable signs including microcephaly, growth retardation, psychomotor retardation and facial dysmorphism.

440
(49.1%)

ethylmalonic encephalopathy

Acrocyanosis Lactic acidosis Petechiae

Autosomal recessive inheritance

Ethylmalonic acid encephalopathy (EE) is defined by elevated excretion of ethylmalonic acid (EMA) with recurrent petechiae, orthostatic acrocyanosis and chronic diarrhoea associated with neurodevelopmental delay, psychomotor regression and hypotonia with brain magnetic resonance imaging (MRI) abnormalities.

441
(49.1%)

mycosis fungoides

Eczema Erythema Lymphadenopathy Lymphoma

Classical mycosis fungoides is the most common type of mycosis fungoides (MF), a form of cutaneous T-cell lymphoma, and is characterized by slow progression from patches to more infiltrated plaques and eventually to tumors.

441
(49.1%)

Spondyloenchondrodysplasia with immune dysregulation

Low-set ears Lymphadenopathy Purpura

Autosomal recessive inheritance

443
(48.9%)

congenital afibrinogenemia

Abnormal bleeding Splenic rupture

Autosomal recessive inheritance

Familial afibrinogenemia is a coagulation disorder characterized by bleeding symptoms due to a complete absence of circulating fibrinogen.

443
(48.9%)

Fanconi anemia, complementation group W

Myelodysplasia Polysplenia Renal hypoplasia

Autosomal recessive inheritance

445
(48.7%)

aplasia cutis congenita-intestinal lymphangiectasia syndrome

Aplasia cutis congenita over the scalp vertex Hypoproteinemia Intestinal lymphangiectasia Lymphopenia

Autosomal recessive inheritance

Aplasia cutis congenita - intestinal lymphangiectasia is an extremely rare association syndrome, described in only two brothers to date (one of which died at 2 months of age), characterized by aplasia cutis congenita of the vertex and generalized edema (as well as hypoproteinemia and lymphopenia) due to intestinal lymphangiectasia. There have been no further descriptions in the literature since 1985.

445
(48.7%)

angioosteohypertrophic syndrome

Abnormality of blood and blood-forming tissues Hyperpigmented nevi and streak Lymphangioma Lymphedema

Sporadic

Angio-osteohypertrophic (AOH) syndrome is 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.

445
(48.7%)

Vici syndrome

Abnormality of the thymus Acidosis Decreased proportion of CD4-positive helper T cells Hypopigmentation of the skin

Autosomal recessive inheritance

Vici syndrome is a very rare and severe congenital multisystem disorder characterized by the principal features of agenesis of the corpus callosum, cataracts, oculocutaneous hypopigmentation, cardiomyopathy and combined immunodeficiency.

445
(48.7%)

CHARGE syndrome

Abnormal palmar dermatoglyphics Aplasia/Hypoplasia of the thymus Hypocalcemia Lymphopenia

Autosomal dominant inheritance Sporadic

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).

449
(48.2%)

chylomicronemia, familial, due to circulating inhibitor of lipoprotein lipase

Hyperlipoproteinemia Splenomegaly

Autosomal dominant inheritance

449
(48.2%)

autoimmune lymphoproliferative syndrome type 2B

Defective B cell activation Eczema Splenomegaly

Autosomal recessive inheritance

Autoimmune lymphoproliferative syndrome (ALPS) with recurrent viral infections is a rare genetic disorder characterized by lymphadenopathy and/or splenomegaly and recurrent infections due to herpes viruses.

451
(48.1%)

MHC class II deficiency

Cholangitis Cutaneous anergy Neutropenia Viral hepatitis

Autosomal recessive inheritance

Immunodeficiency by defective expression of HLA class 2 is a rare primary genetic immunodeficiency disorder characterized by partial or complete absence of human leukocyte antigen class 2 expression resulting in severe defect in both cellular and humoral immune response to antigens. The disorder presents clinically as marked susceptibility to infections, severe malabsorption and failure to thrive and is often fatal in early childhood.

452
(48.0%)

hereditary spherocytosis type 3

Hemolytic anemia Spherocytosis

Autosomal recessive inheritance

Any hereditary spherocytosis in which the cause of the disease is a mutation in the SPTA1 gene.

452
(48.0%)

pyropoikilocytosis, hereditary

Hemolytic anemia Microspherocytosis

Autosomal recessive inheritance

An autosomal recessive inherited severe hemolytic anemia. It is a subtype of hereditary elliptocytosis and is characterized by partial spectrin deficiency.

452
(48.0%)

hereditary spherocytosis type 5

Hemolytic anemia Spherocytosis

Autosomal recessive inheritance

Any hereditary spherocytosis in which the cause of the disease is a mutation in the EPB42 gene.

455
(47.8%)

cyanosis and hepatic disease

Abnormal abdomen morphology Cyanosis

Autosomal recessive inheritance

456
(47.8%)

Fanconi anemia, complementation group S

Anemia Chromosome breakage Low anterior hairline Narrow palate

Autosomal recessive inheritance

457
(47.7%)

IRIDA syndrome

Elevated hepcidin level Hypochromic microcytic anemia Poikilocytosis

Autosomal recessive inheritance

IRIDA (Iron-refractory iron deficiency anemia) syndrome is a rare autosomal recessive iron metabolism disorder characterized by iron deficiency anemia (hypochromic, microcytic) that is often unresponsive to oral iron intake and partially responsive to parenteral iron treatment.

457
(47.7%)

hemolytic anemia due to erythrocyte adenosine deaminase overproduction

Hemolytic anemia Hyperuricemia Stomatocytosis

Autosomal dominant inheritance

Hemolytic anemia due to erythrocyte adenosine deaminase overproduction is a rare, genetic, hematologic disease characterized by mild, chronic hemolytic anemia (due to highly elevated adenosine deaminase activity in red blood cells resulting in their premature destruction), elevated reticulocyte count, splenomegaly and mild hyperbilirubinemia. Other cells and tissues are not affected.

459
(47.6%)

mismatch repair cancer syndrome 1

Abnormal abdomen morphology Cafe-au-lait spot Leukemia

Autosomal recessive inheritance

A rare childhood cancer predisposition syndrome caused by biallelic inheritance of mutations in MLH1, MSH2, MSH6, or PMS2 genes. It is characterized by the development of childhood cancers, usually hematological malignancies and/or brain tumors, and colorectal cancers with multiple intestinal polyps. The majority of patients show signs of neurofibromatosis type 1.

460
(47.3%)

microgastria-limb reduction defect syndrome

Asplenia Biliary tract abnormality Cryptorchidism

Sporadic

This syndrome is characterised by the association of microgastria with a limb reduction defect.

460
(47.3%)

Wolf-Hirschhorn syndrome

Accessory spleen Biliary tract abnormality Cryptorchidism

Autosomal dominant inheritance Sporadic

Wolf-Hirschhorn syndrome (WHS) is a developmental disorder characterized by typical craniofacial features, prenatal and postnatal growth impairment, intellectual disability, severe delayed psychomotor development, seizures, and hypotonia.

462
(47.3%)

proteasome-associated autoinflammatory syndrome 2

Fever Lymphadenopathy Skin rash Thrombocytopenia

Autosomal dominant inheritance

463
(47.3%)

Diamond-Blackfan anemia 17

Anemia Hyperpigmentation of the skin

Autosomal dominant inheritance

463
(47.3%)

oculocerebral hypopigmentation syndrome of Preus

Generalized hypopigmentation High palate Hypochromic anemia

Autosomal recessive inheritance

463
(47.3%)

Fanconi anemia complementation group P

Anemia Cafe-au-lait spot Cryptorchidism

Autosomal recessive inheritance

Any Fanconi anemia in which the cause of the disease is a mutation in the SLX4 gene.

466
(47.2%)

portal hypertension, noncirrhotic

Portal hypertension Splenomegaly

Autosomal recessive inheritance

466
(47.2%)

acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome

Hepatic fibrosis Intellectual disability, mild Splenomegaly

Autosomal recessive inheritance

An autosomal recessive cerebellar ataxia that has material basis in homozygous or compound heterozygous mutation in the SCYL1 gene on chromosome 11q13.

466
(47.2%)

Hurler-Scheie syndrome

Hepatomegaly Micrognathia Splenomegaly

Autosomal recessive inheritance

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.

466
(47.2%)

sarcoidosis, susceptibility to, 2

Hepatomegaly Splenomegaly Uveitis

Autosomal dominant inheritance

Any sarcoidosis in which the cause of the disease is a mutation in the BTNL2 gene.

466
(47.2%)

short-rib thoracic dysplasia 15 with polydactyly

Hepatomegaly Horseshoe kidney Splenomegaly

Autosomal recessive inheritance

466
(47.2%)

spondyloepimetaphyseal dysplasia, Shohat type

Hepatomegaly Splenomegaly Thin vermilion border

Autosomal recessive inheritance

Spondyloepimetaphyseal dysplasia congenita, Shohat type is characterized by severely disproportionate short stature, short limbs, small chest, short neck, thin lips, severe lumbar lordosis, marked genu varum, joint laxity, distended abdomen, mild hepatomegaly and splenomegaly.

466
(47.2%)

Zimmermann-Laband syndrome 1

Hepatomegaly Long penis Splenomegaly

Autosomal dominant inheritance

Any Zimmermann-Laband syndrome in which the cause of the disease is a mutation in the KCNH1 gene.

466
(47.2%)

COACH syndrome 1

Cirrhosis Renal insufficiency Splenomegaly

Autosomal recessive inheritance

A very rare subtype of Joubert syndrome and related disorders (JSRD) characterized by the neurological features of JS associated with congenital hepatic fibrosis (CHF).

466
(47.2%)

paternal uniparental disomy of chromosome 14

Hepatomegaly Inguinal hernia Splenomegaly

Autosomal dominant inheritance Sporadic

466
(47.2%)

syndromic multisystem autoimmune disease due to ITCH deficiency

Dolichocephaly Hepatomegaly Splenomegaly

Autosomal recessive inheritance

466
(47.2%)

Simpson-Golabi-Behmel syndrome type 1

Hepatomegaly Inguinal hernia Splenomegaly

X-linked recessive inheritance

Any Simpson-Golabi-Behmel syndrome in which the cause of the disease is a mutation in the GPC3 gene.

477
(47.1%)

CLOVES syndrome

Capillary malformation Facial asymmetry Splenomegaly

Somatic mosaicism Sporadic

CLOVE syndrome is characterized by Congenital Lipomatous Overgrowth, progressive, complex and mixed truncal Vascular malformations, and Epidermal nevi.

477
(47.1%)

cardiofaciocutaneous syndrome 1

Hydronephrosis Hyperkeratosis Splenomegaly

Autosomal dominant inheritance

Any cardiofaciocutaneous syndrome in which the cause of the disease is a mutation in the BRAF gene.

479
(47.0%)

primary intestinal lymphangiectasia

Abnormal hair morphology Edema Intestinal lymphangiectasia Lymphopenia

Autosomal dominant inheritance

Primary intestinal lymphangiectasia (PIL) is a rare intestinal disease characterized by dilated intestinal lacteals which cause lymph leakage into the small bowel lumen. Clinical manifestations include edema related to hypoalbuminemia (protein-losing enteropathy), asthenia, diarrhea, lymphedema and failure to thrive in children.

480
(47.0%)

thrombophilia due to protein S deficiency, autosomal dominant

Purpura Warfarin-induced skin necrosis

Autosomal dominant inheritance

Autosomal dominant form of hereditary thrombophilia due to congenital protein S deficiency.

480
(47.0%)

thrombophilia due to protein C deficiency, autosomal dominant

Abnormality of the eye Deep venous thrombosis Pulmonary embolism Warfarin-induced skin necrosis

Autosomal dominant inheritance

480
(47.0%)

hereditary hemorrhagic telangiectasia type 4

Cerebral hemorrhage Cyanosis Lip telangiectasia

Autosomal dominant inheritance Heterogeneous

483
(46.9%)

MGAT2-CDG

Abnormal isoelectric focusing of serum transferrin Long eyelashes Midfrontal capillary hemangioma Reduced factor XI activity

Autosomal recessive inheritance

MGAT2-CDG is a form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (large, posteriorly rotated ears with prominent antihelices, convex nasal ridge, open mouth, large and crowded teeth), stereotypic hand movements, seizures, and varying degrees of developmental delay. A bleeding tendency is also observed and this results from diminished platelet aggregation. The disease is caused by loss-of-function mutations in the gene MGAT2 (14q21).

484
(46.9%)

retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Micronodular cirrhosis Proteinuria Retinal hemorrhage Telangiectasia

Autosomal dominant inheritance

Retinal vasculopathy and cerebral leukodystrophy (RVCL) is an inherited group of small vessel diseases comprised of cerebroretinal vasculopathy (CRV), hereditary vascular retinopathy (HRV) and hereditary endotheliopathy with retinopathy, nephropathy and stroke (HERNS); all exhibiting progressive visual impairment as well as variable cerebral dysfunction.

484
(46.9%)

classic homocystinuria

Cutis marmorata Hepatic steatosis Homocystinuria Thromboembolism

Autosomal recessive inheritance

Classical homocystinuria due to cystathionine beta-synthase (CbS) deficiency is characterized by the multiple involvement of the eye, skeleton, central nervous system, and vascular system.

486
(46.8%)

hydroxyacyl glutathione hydrolase deficiency

Elliptocytosis Glyoxalase deficiency

Autosomal dominant inheritance

486
(46.8%)

familial hypobetalipoproteinemia 1

Acanthocytosis Decreased LDL cholesterol concentration Rod-cone dystrophy

Autosomal recessive inheritance

Any hypobetalipoproteinemia in which the cause of the disease is a mutation in the APOB gene.

488
(46.5%)

combined immunodeficiency due to GINS1 deficiency

Dry skin Lymphadenopathy Microcephaly Neutropenia

Autosomal recessive inheritance

489
(46.4%)

glycine N-methyltransferase deficiency

Hepatomegaly Hypermethioninemia

Autosomal recessive inheritance

Glycine N-methyltransferase deficiency (GNMT deficiency) is a very rare condition characterized by persistent and isolated excess levels of methionine in the blood (hypermethioninemia). The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver disease. Methionine may also be increased in urine. However, because elevated levels of methionine in the blood itself is a risk factor for development of neurological signs and symptoms, people with GNMT deficiency can have neurological problems when methionine levelsare greater than 800μmol/L. GNMT deficiency is caused by mutations in the GNMT gene. Inheritance is autosomal recessive. Treatment is not needed in most cases.

489
(46.4%)

long chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Hepatomegaly Hypoglycemia Pigmentary retinopathy

Autosomal recessive inheritance

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a mitochondrial disorder of long chain fatty acid oxidation characterized in most patients by onset in infancy/ early childhood with hypoketotic hypoglycemia, metabolic acidosis, liver disease, hypotonia and frequently cardiac involvement with arrhythmias and/or cardiomyopathy.

489
(46.4%)

CIDEC-related familial partial lipodystrophy

Acanthosis nigricans Hepatic steatosis Hepatomegaly Hypertriglyceridemia

Autosomal recessive inheritance

489
(46.4%)

hyperzincemia with functional zinc depletion

Hepatomegaly Increased serum zinc Osteoporosis

Autosomal dominant inheritance

489
(46.4%)

glycogen storage disease IXa

Hepatomegaly Hypoglycemia Motor delay

X-linked recessive inheritance

Any glycogen storage disease in which the cause of the disease is a mutation in the PHKA2 gene.

489
(46.4%)

combined oxidative phosphorylation defect type 9

Global developmental delay Hepatomegaly Increased serum lactate

Autosomal recessive inheritance

Combined oxidative phosphorylation defect type 9 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly. Laboratory studies report increased plasma lactate and alanine, abnormal liver enzymes and decreased activity of mitochondrial respiratory chain complexes I, III, IV, and V.

489
(46.4%)

glycogen storage disease VI

Failure to thrive in infancy Hepatomegaly Hypoglycemia

Autosomal recessive inheritance

Liver phosphorylase deficiency, or glycogen storage disease type 6b (Hers' disease, GSD 6b) is a benign and rare form of glycogen storage disease.

489
(46.4%)

Amish lethal microcephaly

Hepatomegaly Lactic acidosis Progressive microcephaly

Autosomal recessive inheritance

Amish lethal microcephaly is a very rare syndrome characterized by extreme microcephaly and early death, within the first year.

489
(46.4%)

Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young

Hepatomegaly Proteinuria

Autosomal dominant inheritance

Any Fanconi syndrome in which the cause of the disease is a mutation in the HNF4A gene.

489
(46.4%)

carnitine palmitoyl transferase II deficiency, severe infantile form

Hepatomegaly Hypoketotic hypoglycemia Macrovesicular hepatic steatosis Seizure

Autosomal recessive inheritance

The severe infantile form of carnitine palmitoyltransferase II (CPT II) deficiency, an inherited disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the early-onset form of the disease.

489
(46.4%)

fructose-1,6-bisphosphatase deficiency

Hepatomegaly Irritability Metabolic acidosis

Autosomal recessive inheritance

Fructose-1,6-biphosphatase (FBP) deficiency is a disorder of fructose metabolism characterized by recurrent episodes of fasting hypoglycemia with lactic acidosis, that may be life-threatening in neonates and infants.

489
(46.4%)

retinitis pigmentosa 59

Cryptorchidism Cystoid macular edema Hepatomegaly

Autosomal recessive inheritance

Any retinitis pigmentosa in which the cause of the disease is a mutation in the DHDDS gene.