1497
(53.0%)

Cranio-osteoarthropathy

Deviation of finger Large fontanelles

Cranio-osteoarthropathy (COA) is a form of primary hypertrophic osteoarthropathy (see this term) characterized by delayed closure of the cranial sutures and fontanels, digital clubbing, arthropathy, and periostosis.

1497
(53.0%)

16p13.11 microduplication syndrome

Dolichocephaly Hand polydactyly

16p13.11 microduplication syndrome is a recently described syndrome associated with variable clinical features including behavioral abnormalities, developmental delay, congenital heart defects and skeletal anomalies.

1497
(53.0%)

Cerebellar ataxia-hypogonadism syndrome

Brachycephaly Clinodactyly of the 5th finger

Autosomal recessive inheritance

Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome (see this term).

1497
(53.0%)

Krabbe disease

Abnormal thumb morphology Cloverleaf skull

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.

1497
(53.0%)

Familial glucocorticoid deficiency

Arachnodactyly Relative macrocephaly

Familial glucocorticoid deficiency (FGD) is a group of primary adrenal insufficiencies characterized clinically by neonatal hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections, and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency.

1506
(53.0%)

Wild type ABeta2M amyloidosis

Abnormal shoulder morphology Abnormality of the thenar eminence Macroglossia

Dialysis-related amyloidosis (DRA), is a type of amyloidosis (see this term) affecting patients with chronic kidney disease (CKD), on long term dialysis characterized by the accumulation of amyloid fibrils consisting of beta 2 microglobulin (β2M) deposits in the musculoskeletal system leading to carpal tunnel syndrome (CTS), chronic arthropathy, cystic bone lesions, destructive osteoarthropathy, and pathologic fractures.

1506
(53.0%)

Squamous cell carcinoma of the esophagus

Chest pain Oral leukoplakia Palmoplantar hyperkeratosis

Esophageal squamous cell carcinoma (ESCC) is a type of esophageal carcinoma (EC; see this term) that can affect any part of the esophagus, but is usually located in the upper or middle third.

1506
(53.0%)

Primary sclerosing cholangitis

Chest pain Palmar telangiectasia Sialadenitis

Autosomal dominant inheritance Multifactorial inheritance

Primary sclerosing cholangitis (PSC) is a rare, slowly progressive liver disease characterized by inflammation and destruction of the intra- and/or extra-hepatic bile ducts that lead to cholestasis, liver fibrosis, liver cirrhosis and ultimately liver failure.

1509
(53.0%)

Tako-Tsubo cardiomyopathy

Brachydactyly Short neck

Takotsubo cardiomyopathy (TC) is a recently described acute cardiac syndrome that mimics acute myocardial infarction and is characterized by ischemic chest symptoms, an elevated ST segment on electrocardiogram, and elevated levels of cardiac disease markers.

1510
(52.9%)

Cystic echinococcosis

Clubbing Orbital cyst Pectus carinatum

Hydatidosis or cyst hydatic disease is a cosmopolitan larval cestodosis caused principally by the Echinococcus granulosus tapeworm, the adult form of which parasitises the intestine of dogs. Hydatidosis generally affects large domestic herbivores; humans are dead-end hosts, infected through contact with herding dogs or through ingestion of food contaminated with canine excrement.

1511
(52.9%)

Chronic inflammatory demyelinating polyneuropathy

Drooling Hand muscle weakness Scoliosis

A chronic monophasic, progressive or relapsing symmetric sensorimotor disorder characterized by progressive muscular weakness with impaired sensation, absent or diminished tendon reflexes and elevated cerebrospinal fluid (CSF) proteins.

1512
(52.8%)

Actinic prurigo

Cheilitis Conjunctivitis

Autosomal dominant inheritance Multifactorial inheritance

A rare, chronic, photodermatosis disease characterized by intensely pruritic, polymorphic, erythematous, excoriated and/or lichenified papules, macules, plaques and nodules, occurring on sun-exposed areas of the skin (particularly face, nose, lips, and ears), frequently associating cheilitis (especially of the lower lip) and conjuctivitis, which are present year-round or only in the spring/summer (depending on geographic location), observed mainly in Native Americans and Mestizos. Cheilitis may be the sole clinical presentation. Histologically, the presence of lymphoid follicles in mucosa is pathognomonic.

1512
(52.8%)

Pseudopelade of Brocq

Aplasia/Hypoplasia of the eyebrow Cheilitis Recurrent skin infections Sparse scalp hair

Pseudo-pelade of Brocq is a rare hair abnormality characterized by onset in adulthood of soft, irregular, flesh-toned patches of alopecia primarily in the parietal and vertex portions of the scalp, without follicular hyperkeratosis or perifollicular inflammation.

1514
(52.8%)

Eng-Strom syndrome

Brachydactyly Camptodactyly of finger Pectus excavatum

Autosomal dominant inheritance

A rare disorder characterized by intrauterine growth retardation and intermittent locking of the finger joints. It has been described in two individuals: a mother and her daughter. The mode of transmission is autosomal dominant.

1515
(52.8%)

Dentinogenesis imperfecta

Femur fracture Macrocephaly Periorbital fullness Taurodontia

Dentinogenesis imperfecta (DGI) is a hereditary dentin defect (see this term) characterized by abnormal dentin structure resulting in abnormal tooth development.

1516
(52.8%)

Thin ribs-tubular bones-dysmorphism syndrome

Abnormal palate morphology Abnormality of pelvic girdle bone morphology Macrocephaly Slender long bone

An extremely rare, lethal, primary bone dysplasia characterized by thin ribs, thin long bones, high-arched palate and facial features of frontal bossing and low-set, posteriorly rotated ears. Bilateral cryptorchidism may be also observed. There have been no further descriptions in the literature since 1990.

1516
(52.8%)

Permanent neonatal diabetes mellitus

Downturned corners of mouth Epiphyseal dysplasia Prominent metopic ridge

Autosomal dominant inheritance Autosomal recessive inheritance

Permanent neonatal diabetes mellitus (PNDM) is a monogenic form of neonatal diabetes (NDM, see this term) characterized by persistent hyperglycemia within the first 12 months of life in general, requiring continuous insulin treatment.

1518
(52.7%)

AL amyloidosis

Keratoconjunctivitis sicca Macroglossia Pedal edema Vertebral compression fractures

A plasma cell disorder characterized by the aggregation and deposition of insoluble amyloid fibrils derived from misfolding of monoclonal immunoglobulin light chains usually produced by a plasma cell tumor. It usually presents as primary systemic amyloidosis (PSA) with multiple organ involvement and less frequently as primary localized amyloidosis (PLA) restricted to a single organ.

1519
(52.7%)

Distal monosomy 10q

Microcephaly Short philtrum

Autosomal dominant inheritance Sporadic

Distal monosomy 10q is a chromosomal anomaly involving terminal deletion of the long arm of chromosome 10 and is characterized by facial dysmorphism, pre- and postnatal growth retardation, cardiac and genital anomalies, and developmental delay.

1519
(52.7%)

AICA-ribosiduria

Brachycephaly Thin upper lip vermilion Wide mouth

Autosomal recessive inheritance

An extremely severe inborn error of purine biosynthesis characterized clinically in the single reported case to date by profound intellectual deficit, epilepsy, dysmorphic features of the knees, elbows, and shoulders and congenital blindness.

1519
(52.7%)

Faciocardiorenal syndrome

Narrow mouth Plagiocephaly Smooth philtrum

Autosomal recessive inheritance

A very rare syndrome characterized by intellectual deficit, horseshoe kidney, and congenital heart defects.

1519
(52.7%)

Adenylosuccinate lyase deficiency

Brachycephaly Thin upper lip vermilion

Autosomal recessive inheritance

A disorder of purine metabolism characterized by intellectual disability, psychomotor delay and/or regression, seizures, and autistic features.

1519
(52.7%)

Fried syndrome

High palate Scoliosis Short philtrum Thickened calvaria

Fried syndrome is a rare X-linked mental retardation (XLMR) syndrome characterized by psychomotor delay, intellectual deficit, hydrocephalus, and mild facial anomalies.

1519
(52.7%)

Encephalopathy due to sulfite oxidase deficiency

Full cheeks Long philtrum Microcephaly

Encephalopathy due to sulfite oxidase deficiency is a rare neurometabolic disorder characterized by seizures, progressive encephalopathy and lens dislocation.

1519
(52.7%)

X-linked intellectual disability-cerebellar hypoplasia syndrome

Abnormality of the philtrum Frontal bossing Long face

X-linked recessive inheritance X-linked dominant inheritance

X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.

1519
(52.7%)

15q14 microdeletion syndrome

Abnormality of the dentition Microcephaly Smooth philtrum

Autosomal dominant inheritance

15q14 microdeletion syndrome is a recently described syndrome characterized by developmental delay, short stature and facial dysmorphism.

1519
(52.7%)

SSR4-CDG

Abnormality of upper lip vermillion Microcephaly Wide mouth

X-linked recessive inheritance

SSR4-CDG is a form of congenital disorders of N-linked glycosylation characterized by neurologic abnormalities (global developmental delay in language, social skills and fine and gross motor development, intellectual disability, hypotonia, microcephaly, seizures/epilepsy), facial dysmorphism (deep set eyes, large ears, hypoplastic vermillion of upper lip, large mouth with widely spaced teeth), feeding problems often due to chewing difficulties and aversion to food with certain textures, failure to thrive, gastrointestinal abnormalities (reflux or vomiting) and strabismus. The disease is caused by mutations in the gene SSR4 (Xq28).

1519
(52.7%)

Severe intellectual disability-progressive spastic diplegia syndrome

Microcephaly Thin upper lip vermilion

Autosomal dominant inheritance

Severe intellectual disability-progressive spastic diplegia syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by intellectual disability, significant motor delay, severe speech impairment, early-onset truncal hypotonia with progressive distal hypertonia/spasticity, microcephaly, and behavioral anomalies (autistic features, aggression or auto-aggressive behavior, sleep disturbances). Variable facial dysmorphism includes broad nasal tip with small alae nasi, long and/or flat philtrum, thin upper lip vermillion. Visual impairment (strabismus, hyperopia, myopia) is commonly associated.

1529
(52.7%)

Hereditary orotic aciduria

Downslanted palpebral fissures Hip dysplasia Wide nasal bridge

Autosomal recessive inheritance

A rare autosomal recessive disorder characterized by retarded growth, anemia and excessive urinary excretion of orotic acid. It is due to a severe deficiency in the activity of the pyrimidine pathway enzyme uridine 5'-monophosphate (UMP) synthase (bifunctional enzyme containing two activities: orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase), coded by a single gene (UMPS) localized to chromosome 3q13.

1530
(52.6%)

Epidermolysis bullosa acquisita

Conjunctivitis Syndactyly

A rare, chronic, incurable, sub epithelial autoimmune bullous disease characterized by the presence of tissue bound autoantibodies against type VII collagen within the basement membrane zone of the dermal-epidermal junction of stratified squamous epithelia. The patient's serum may also have anti-type VII collagen autoantibodies. The clinical presentation is varied, and may involve the skin, oral mucosa and the upper third of the esophagus. The classical presentation is reminiscent of hereditary dystrophic epidermolysis bullosa (EB) with skin fragility, blisters and erosions and skin scarring. Other non-classical clinical presentations include an inflammatory bullous pemphigoid-like eruption, a mucous membrane pemphigoid-like eruption, and an IgA bullous dermatosis-like disease.

1530
(52.6%)

Hypocomplementemic urticarial vasculitis

Clubbing Conjunctivitis

Hypocomplementemic urticarial vasculitis (HUV) is an immune complex-mediated small vessel vasculitis characterized by urticaria and hypocomplementemia (low C1q with or without low C3 and C4), and usually associated with circulating anti-C1q autoantibodies. Arthritis, pulmonary disease, ocular inflammation, and glomerulonephritis are common systemic manifestations.

1530
(52.6%)

Cryoglobulinemic vasculitis

Clubbing Keratoconjunctivitis sicca

Autosomal dominant inheritance

Mixed cryoglobulinemia (MC) is a rare multisystem disease characterized by the presence of circulating cryoprecipitable immune complexes in the serum, manifested clinically by a classical triad of purpura, weakness and arthralgia.

1533
(52.6%)

Lambert-Eaton myasthenic syndrome

Back pain Keratoconjunctivitis sicca Limb muscle weakness Xerostomia

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune, presynaptic disorder of neuromuscular transmission characterized by fluctuating muscle weakness and autonomic dysfunction frequently associated with small-cell lung cancer (SCLC).

1534
(52.6%)

Severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome

Coarse facial features Finger joint hypermobility Genu valgum

1535
(52.5%)

Chronic nonbacterial osteomyelitis/Chronic recurrent multifocal osteomyelitis

Abnormality of the metaphysis Craniofacial osteosclerosis

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a chronic autoinflammatory syndrome that is characterized by multiple foci of painful swelling of bones, mainly in the metaphyses of the long bones, in addition to the pelvis, the shoulder girdle and the spine.

1536
(52.5%)

Focal palmoplantar and gingival keratoderma

Focal friction-related palmoplantar hyperkeratosis Gingival overgrowth

Autosomal dominant inheritance

Focal palmoplantar and gingival keratoderma is a very rare form of focal palmoplantar keratoderma characterized by painful circumscribed hyperkeratotic lesions on weight-bearing areas of soles, moderate focal hyperkeratosis of palmar pressure-related areas and an asymptomatic leukokeratosis confined to labial- and lingual- attached gingiva. Additional occasional features may include hyperhidrosis, follicular keratosis and extended oral mucosa involvement.

1536
(52.5%)

Lacrimoauriculodentodigital syndrome

Hypodontia Split hand Xerostomia

Autosomal dominant inheritance

Lacrimoauriculodentodigital (LADD) syndrome is a multiple congenital anomaly syndrome characterized by hypoplasia, aplasia or atresia of the lacrimal system; anomalies of the ears and hearing loss; hypoplasias, apalsias or atresias of the salivary glands; dental anomalies and digital malformations.

1536
(52.5%)

Naegeli-Franceschetti-Jadassohn syndrome

Abnormality of dental enamel Palmoplantar hyperkeratosis

Autosomal dominant inheritance

Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is a rare ectodermal dysplasia that affects the skin, sweat glands, nails, and teeth.

1536
(52.5%)

Anonychia with flexural pigmentation

Abnormal skin morphology of the palm Carious teeth Convex nasal ridge

Autosomal dominant inheritance

A disorder that is characterised by anonychia and skin abnormalities (hyper- and hypopigmentation in axillae and groins, dry palmar and plantar skin leading to sore and cracked soles). It has been described in a mother and her two children. The mode of transmission is autosomal dominant.

1536
(52.5%)

Distal nebulin myopathy

High palate Weakness of the intrinsic hand muscles

Distal nebulin myopathy is a rare, slowly progressive, autosomal recessive distal myopathy characterized by early onset of predominantly distal muscle weakness and atrophy affecting lower leg extensor muscles, finger extensors and neck flexors. Muscle histology does not always show nemaline rods.

1536
(52.5%)

Mutilating palmoplantar keratoderma with periorificial keratotic plaques

Abnormality of the tongue Palmoplantar hyperhidrosis

Mutilating palmoplantar keratoderma (PPK) with periorificial keratotic plaques (also known as Olmsted syndrome) is a hereditary palmoplantar keratoderma characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma and periorificial keratotic plaques.

1542
(52.4%)

Juvenile myoclonic epilepsy

Abnormality of the mouth Palmoplantar hyperhidrosis

Autosomal dominant inheritance Autosomal recessive inheritance Multifactorial inheritance

Juvenile myoclonic epilepsy is the most common hereditary idiopathic generalized epilepsy syndrome and is characterized by myoclonic jerks of the upper limbs on awakening, generalized tonic-clonic seizures manifesting during adolescence and triggered by sleep deprivation, alcohol intake, and cognitive activities, and typical absence seizures (30% of cases).

1543
(52.3%)

Camptodactyly-fibrous tissue hyperplasia-skeletal dysplasia syndrome

Arachnodactyly Coarse facial features Scoliosis

Camptodactyly - fibrous tissue hyperplasia - skeletal dysplasia syndrome is an extremely rare chondrodysplastic malformation syndrome that is characterized by the combination of arachnodactyly, becoming evident at around the age of 10, camptodactyly (hammertoes) and scoliosis. A mild facial dysmorphism including a broad nose and flaring nostrils, and a mild intellectual disability were also noted. Camptodactyly - fibrous tissue hyperplasia - skeletal dysplasia syndrome has been described once in 3 siblings and is suspected to follow autosomal recessive transmission. There have been no further descriptions in the literature since 1972.

1543
(52.3%)

Parana hard skin syndrome

Pectus carinatum Round face Tapered finger

Autosomal recessive inheritance

Parana hard skin syndrome is a rare genetic skin disorder characterized by very early-onset of progressive skin thickening over the entire body (except for eyelids, neck and ears), progressively limited joint mobility with gradual freezing of joints, and eventual severe chest and abdomen movement restriction, manifesting with restrictive pulmonary disease, which may lead to death. Additional features include severe growth restriction and osteoporosis. There have been no further descriptions in the literature since 1974.

1543
(52.3%)

Arthrogryposis-oculomotor limitation-electroretinal anomalies syndrome

Arachnodactyly Pectus excavatum Triangular face

Autosomal dominant inheritance Autosomal recessive inheritance

Distal arthrogryposis type 5 is an inherited developmental defect syndrome characterized by multiple congenital contractures of limbs, without primary neurologic and/or muscle disease that affects limb function, and ocular anomalies (ptosis, external ophtalmoplegia and/or strabismus). Intelligence is normal.

1543
(52.3%)

Idiopathic pulmonary fibrosis

Clubbing of fingers Epistaxis Scoliosis

Autosomal dominant inheritance

Idiopathic pulmonary fibrosis (IPF) is a nonneoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known cause.

1547
(52.3%)

Dent disease

Delayed epiphyseal ossification Enlargement of the wrists Microcephaly

Dent disease is a rare genetic renal tubular disease characterized by manifestations of proximal tubule dysfunction.

1548
(52.3%)

Renal tubular dysgenesis

Bilateral single transverse palmar creases Microcephaly

Renal tubular dysgenesis is a rare disorder of the fetus characterized by absent or poorly developed proximal tubules of the kidneys, persistent oligohydramnios, leading to Potter sequence (facial dysmorphism with large and flat low-set ears, lung hypoplasia, arthrogryposis and limb positioning defects), and skull ossification defects. It can be acquired during fetal development due to drugs taken by the mother or certain disorders (twin-twin transfusion syndrome, TTTS) or inherited in an autosomal recessive manner.

1548
(52.3%)

Triple A syndrome

Abnormality of the hypothenar eminence Microcephaly

Autosomal recessive inheritance

Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration.

1550
(52.3%)

Autosomal recessive limb-girdle muscular dystrophy type 2U

Macroglossia Scapular winging

Autosomal recessive inheritance

A rare subtype of autosomal recessive limb-girdle muscular dystrophy disorder characterized by infantile to childhood-onset of slowly progressive, principally proximal, shoulder and/or pelvic-girdle muscular weakness that typically presents with positive Gowers' sign and is associated with elevated creatine kinase levels, hyporeflexia, joint and achilles tendon contractures, and muscle hypertrophy, usually of the thighs, calves and/or tongue. Other highly variable features include cerebellar, cardiac and ocular abnormalities.

1550
(52.3%)

Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome

Kyphoscoliosis Proximal muscle weakness in upper limbs Tongue atrophy

1550
(52.3%)

Otofaciocervical syndrome

Abnormal clavicle morphology High palate Scapular winging

Otofaciocervical syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit. Vertebral defects and short stature may also be associated.

1550
(52.3%)

Autosomal recessive limb-girdle muscular dystrophy type 2C

Macroglossia Scapular winging Scoliosis

Autosomal recessive inheritance

A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by a childhood onset of progressive shoulder and pelvic girdle muscle weakness and atrophy frequently associated with calf hypertrophy, diaphragmatic weakness, and/or variable cardiac abnormalities. Mild to moderate elevated serum creatine kinase levels and positive Gowers sign are reported.

1550
(52.3%)

Hemophilia A

Abnormality of the elbow Back pain Gingival bleeding

Autosomal dominant inheritance X-linked recessive inheritance

Hemophilia A is the most common form of hemophilia (see this term) characterized by spontaneous or prolonged hemorrhages due to factor VIII deficiency.

1555
(52.3%)

Bencze syndrome

Submucous cleft hard palate Telecanthus

Autosomal dominant inheritance

Bencze syndrome or hemifacial hyperplasia with strabismus is a malformation syndrome involving the abnormal growth of the facial skeleton as well as its soft tissue structure and organs, and is characterized by mild facial asymmetry with unaffected neurocranium and eyeballs, as well as by esotropia, amblyopia and/or convergent strabismus, and occasionally submucous cleft palate. Transmission is autosomal dominant. There have been no further descriptions in the literature since 1979.

1556
(52.2%)

Optic pathway glioma

Lisch nodules Pseudoarthrosis Scoliosis

Optic pathway glioma (OPG) is a benign tumor that develop along the optic nerve (chiasm, tracts, and radiations) characterized by impairment or loss of vision and may be accompanied by diencephalic symptoms such as reduced growth and alteration in sleeping patterns. OPG are often linked to neurofibromatosis type 1 (NF1, see this term).

1557
(52.2%)

Ameloonychohypohidrotic syndrome

Abnormality of dental enamel Everted lower lip vermilion

Autosomal dominant inheritance

A rare ectodermal dysplasia syndrome characterized by the association of hypocalcified and hypoplastic tooth enamel, distal finger and toenail onycholysis with subungueal hyperkeratosis, and functional hypohidrosis. Additional manifestations include seborrheic scalp dermatitis and rough, dry skin. Lacrymal punctae may be occasionally absent. There have been no further descriptions in the literature since 1975.

1557
(52.2%)

Hereditary folate malabsorption

Cerebral calcification Cheilitis Glossitis

Autosomal recessive inheritance

Hereditary folate malabsorption (HFM) is an inherited disorder of folate transport characterized by a systemic and central nervous system (CNS) folate deficiency manifesting as megaloblastic anemia, failure to thrive, diarrhea and/or oral mucositis, immunologic dysfunction and neurological disorders.

1557
(52.2%)

Glucagonoma

Angular cheilitis Glossitis Pancreatic calcification

Glucagonoma is a rare, functioning type of pancreatic neuroendocrine tumor (PNET; see this term) that hypersecretes glucagon, leading to a syndrome comprised of necrolytic migratory erythema, diabetes mellitus, anemia, weight loss, mucosal abnormalities, thromboembolism, gastrointestinal and neuropsychiatric symptoms.

1560
(52.2%)

X-linked intellectual disability, Hedera type

Drooling Hypomimic face Hyporeflexia of upper limbs Scoliosis

X-linked recessive inheritance

X-linked intellectual disability, Hedera type is a rare X-linked intellectual disability syndrome characterized by an onset in infancy of delayed motor and speech milestones, generalized tonic-clonic seizures and drop attacks, and mild to moderate intellectual disability. Additional, less common manifestations include scoliosis, ataxia (resulting in progressive gait disturbance), and bilateral pes planovalgus. Physical appearance is normal with no dysmorphic features reported.

1561
(52.1%)

Tolosa-Hunt syndrome

Blepharospasm Chemosis Trismus

Tolosa-Hunt syndrome is an ophthalmoplegic syndrome, affecting all age groups, characterized by acute attacks (lasting a few days to a few weeks) of periorbital pain, ipsilateral ocular motor nerve palsies, ptosis, disordered eye movements and blurred vision usually caused by a non-specific inflammatory process in the cavernous sinus and superior orbital fissure. It has an unpredicatable course with spontaneous remission occurring in some and recurrence of attacks in others.

1561
(52.1%)

Cholangiocarcinoma

Limbal dermoid Trismus

Cholangiocarcinoma (CCA) is a biliary tract cancer (BTC, see this term) originating in the epithelium of the biliary tree, either intra or extra hepatic.

1563
(52.1%)

Milroy disease

Ankle swelling Epicanthus

Milroy disease is a frequent form of primary lymphedema (see this term) characterized generally by painless, chronic lower-limb lymphedema found at birth or developing in the early neonatal period.

1563
(52.1%)

Autosomal dominant spastic ataxia type 1

Abnormal eyelid morphology Pes cavus

Autosomal dominant inheritance

A rare, genetic, autosomal dominant spastic ataxia disorder characterized by lower-limb spasticity and ataxia in the form of head jerks, ocular movement abnormalities, dysarthria, dysphagia and gait disturbances.

1563
(52.1%)

Netherton syndrome

Hemihypertrophy Sparse and thin eyebrow Sparse eyelashes

Autosomal recessive inheritance

Netherton syndrome (NS) is a skin disorder characterized by congenital ichthyosiform erythroderma (CIE), a distinctive hair shaft defect (trichorrhexis invaginata; TI) and atopic manifestations.

1566
(52.0%)

Spastic paraplegia-severe developmental delay-epilepsy syndrome

Downturned corners of mouth Hip dislocation Microcephaly

Autosomal recessive inheritance

Spastic paraplegia-severe developmental delay-epilepsy syndrome is a rare, genetic, complex spastic paraplegia disorder characterized by an infantile-onset of psychomotor developmental delay with severe intellectual disability and poor speech acquisition, associated with seizures (mostly myoclonic), muscular hypotonia which may be noted at birth, and slowly progressive spasticity in the lower limbs leading to severe gait disturbances. Ocular abnormalities and incontinence are commonly associated. Other symptoms may include verbal dyspraxia, hypogenitalism, macrocephaly and sensorineural hearing loss, as well as dystonic movements and ataxia with upper limb involvement.

1566
(52.0%)

Congenital muscular dystrophy with intellectual disability

Abnormality of the tongue muscle Facial palsy Hip dislocation Microcephaly

Congenital muscular dystrophy with intellectual disability is a rare, genetic, congenital muscular dystrophy due to dystroglycanopathy disorder characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy and delayed or arrested motor development, associated with mild to severe intellectual disability and variable brain abnormalities on neuroimaging studies. Feeding difficulties, joint and spinal deformities, respiratory insufficiency, and ocular anomalies (e.g. strabismus, retinal dystrophy, oculomotor apraxia) may be associated. Decreased or absent alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed.

1568
(51.8%)

Bruck syndrome

Bowing of the long bones Triangular face Wormian bones

Bruck syndrome is characterised by the association of osteogenesis imperfecta and congenital joint contractures.

1568
(51.8%)

Osteoporosis-pseudoglioma syndrome

Frontal bossing Metaphyseal widening Preauricular skin tag

Autosomal recessive inheritance

Osteoporosis pseudoglioma syndrome is a very rare autosomal recessive disorder characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures.

1570
(51.8%)

Syndactyly type 6

Frontal bossing Syndactyly

Syndactyly type 6 is a rare, genetic, non-syndromic, congenital limb malformation disorder characterized by unilateral fusion of second to fifth fingers, amalgamation of distal phalanges in a knot-like structure, and second- and third-toe fusion. Some individuals present only with webbing between second and third toes, without involvement of fingers.

1570
(51.8%)

Isolated scaphocephaly

Dolichocephaly Frontal bossing Syndactyly

Isolated scaphocephaly is a form of nonsyndromic craniosynostosis characterized by premature fusion of the sagittal suture.

1570
(51.8%)

Biemond syndrome type 2

Mandibulofacial dysostosis Polydactyly

Autosomal recessive inheritance

Biemond syndrome type 2 (BS2) is a rare genetic neurological and developmental disorder reported in a very small number of patients with a poorly defined phenotype which includes iris coloboma, short stature, obesity, hypogonadism, postaxial polydactyly, and intellectual disability. Hydrocephalus and facial dysostosis were also reported. BS2 shares features with Bardet-Biedl syndrome. There have been no further descriptions in the literature since 1997.

1570
(51.8%)

Mulibrey nanism

Macrocephaly Syndactyly Triangular face

Autosomal recessive inheritance

A rare developmental defect during embryogenesis characterized by growth delay and multiorgan manifestations.

1574
(51.8%)

Autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome

Movement abnormality of the tongue Upper limb hypertonia

Autosomal recessive inheritance

A rare, genetic, autosomal recessive spastic ataxia disease characterized by onset in early childhood of spastic paraparesis, cerebellar ataxia, dysarthria and optic atrophy.

1574
(51.8%)

Oculopharyngodistal myopathy

Difficulty in tongue movements Distal upper limb amyotrophy

Autosomal dominant inheritance Autosomal recessive inheritance

A rare, genetic neuromuscular disease characterized by progressive external ocular, facial and pharyngeal muscle weakness, leading to variable degrees of ptosis, ophthalmoparesis, facial muscle atrophy, dysarthria and dysphagia, as well as distal muscle weakness and atrophy of lower and upper extremities. Respiratory muscle involvement is common, but sensorineural hearing loss, asymmetrical extremity weakness and severe proximal weakness are rare.

1574
(51.8%)

Choreoacanthocytosis

Difficulty in tongue movements Distal upper limb muscle weakness

Autosomal recessive inheritance

Chorea-acanthocytosis (ChAc) is a form of neuroacanthocytosis (see this term) and is characterized clinically by a Huntington disease-like phenotype with progressive neurological symptoms including movement disorders, psychiatric manifestations and cognitive disturbances.

1577
(51.7%)

Ring chromosome 3 syndrome

Dacryocystitis Sialadenitis Sinusitis

Ring chromosome 3 syndrome is a rare chromosomal anomaly syndrome with a highly variable phenotype principally characterized by pre- and postnatal growth retardation, short stature, developmental delay, mild to severe intellectual disability, microcephaly and mild dysmorphic features (incl. triangular face, dysplastic ears, upslanting palpebral fissures, epicanthic folds, broad nasal bridge, full nasal tip, long philtrum, downturned corners of the mouth, and micro/retrognathia). Additional manifestations reported include hypotonia, mild articular limitation, hearing loss, digital anomalies (i.e. clinodacytyly, brachydactyly), café-au-lait patches and hypospadias.

1577
(51.7%)

Plague

Glossitis Keratoconjunctivitis Sinusitis

Plague is a severe bacterial infection caused by the Gram-negative bacterium Yersinia pestis.

1577
(51.7%)

Relapsing polychondritis

Arthritis Conjunctivitis Recurrent aphthous stomatitis Recurrent sinusitis

Relapsing polychondritis (RP) is a rare, clinically heterogeneous, multisystemic inflammatory disease characterized by inflammation of the cartilage and proteoglycan rich structures leading to cartilage damage with joint, ocular and cardiovascular involvement.

1577
(51.7%)

Eosinophilic granulomatosis with polyangiitis

Conjunctival nodule Sialadenitis Sinusitis

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic vasculitis of small-to medium vessels, characterized by asthma, transient pulmonary infiltrates, and hypereosinophilia.

1581
(51.7%)

Neonatal ichthyosis-sclerosing cholangitis syndrome

Abnormality of dental enamel Hypodontia Sparse and thin eyebrow Sparse eyelashes

Autosomal recessive inheritance

Neonatal ichthyosis-sclerosing cholangitis (NISCH syndrome) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis.

1581
(51.7%)

Hermansky-Pudlak syndrome

Abnormality of dental enamel Epistaxis Long eyelashes

Hermansky-Pudlak syndrome (HSP) is a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and, in some cases, neutropenia, pulmonary fibrosis, or granulomatous colitis. HPS comprises eight known disorders (HPS-1 to HPS-8), the majority of which present with the same clinical phenotype to varying degrees of severity.

1581
(51.7%)

Pilomatrixoma

Calcinosis cutis Chalazion Ranula

Autosomal dominant inheritance Somatic mutation

Pilomatrixoma is a rare and benign hair cell-derived tumor occurring mostly in young adults (usually under the age of 20) and characterized as a 3-30 mm solitary, painless, firm, mobile, deep dermal or subcutaneous tumor, most commonly found in the head, neck or upper extremities. When superficial, the tumors tint the skin blue-red. Multiple pilomatrixomas are seen in myotonic dystrophy, Gardner syndrome, Rubinstein-Taybi syndrome, and Turner syndrome (see these terms).

1584
(51.7%)

Postaxial tetramelic oligodactyly

Abnormality of finger Abnormality of the metacarpal bones

Autosomal dominant inheritance

Postaxial tetramelic oligodactyly is a rare, genetic, congenital limb malformation disorder characterized by isolated, postaxial oligodactyly in all four extremities. Patients present a consistent pattern of malformation ranging from complete absence of the 5th metacarpals, metatarsals and phalanges to complete absence of the 5th metacarpals and metatarsals, with some residual distal 5th phalanges. There have been no further descriptions in the literature since 1993.

1585
(51.7%)

Adenylosuccinate synthetase-like 1-related distal myopathy

Distal upper limb muscle weakness Impaired mastication

1586
(51.6%)

Chromomycosis

Cicatricial ectropion Epistaxis Sinusitis

Chromomycosis is a chronic cutaneous and subcutaneous fungal infection, found mainly in subtropical and tropical areas (in soil and plant debris and transmitted by traumatic inoculation), and characterized clinically by slow growing, verrucous nodules, squamous plaques, or chronic limited lesions which are most commonly found on the lower limbs and which are characterized histologically by the presence of muriform cells. It is caused by dematiaceous fungi, with the main etiological agents being Fonsecaea pedrosoi, Phialophora verrucosa and Cladophialophora carrionii. Rarely, it can be caused by Rhinocladiella aquaspersa.

1586
(51.6%)

Central serous chorioretinopathy

Chalazion Sinusitis

1588
(51.6%)

Autosomal dominant hyper-IgE syndrome

Abnormality of the dentition Cleft palate Sinusitis

Autosomal dominant inheritance

A very rare primary immunodeficiency disorder characterized by the clinical triad of high serum IgE (>2000 IU/ml), recurring staphylococcal skin abscesses, and recurrent pneumonia with formation of pneumatoceles.

1589
(51.6%)

Optic disc pit

Cleft lip Orbital cyst Retinopathy

1590
(51.6%)

Tumor necrosis factor receptor 1 associated periodic syndrome

Abnormality of the sacroiliac joint Chest pain Conjunctivitis

Autosomal dominant inheritance

Tumor necrosis factor receptor 1 associated periodic syndrome (TRAPS) is a periodic fever syndrome, characterized by recurrent fever, arthralgia, myalgia and tender skin lesions lasting for 1 to 3 weeks, associated with skin, joint, ocular and serosal inflammation and complicated by secondary amyloidosis (see this term).

1591
(51.6%)

Adult-onset distal myopathy due to VCP mutation

Back pain Facial diplegia Intrinsic hand muscle atrophy Scapular winging

A rare, genetic distal myopathy disorder characterized by middle age-onset of distal leg muscle weakness, atrophy in the anterior compartment resulting in foot drop, without proximal or scapular skeletal muscle weakness. Rapidly progressive dementia, Paget disease of bone and hand weakness have been reported. Muscle biopsy shows pronounced myopathic changes with rimmed vacuoles.

1591
(51.6%)

Autosomal recessive limb-girdle muscular dystrophy type 2L

Facial palsy Flexion contracture of finger Scapular winging Wrist flexion contracture

Autosomal recessive inheritance

A form of limb-girdle muscular dystrophy most often characterized by an adult onset (but ranging from 11 to 51 years) of mainly proximal lower limb weakness, with difficulties standing on tiptoes being one of the initial signs. Proximal upper limb and distal lower limb weakness is also common, as well as atrophy of the quadriceps (most commonly), biceps brachii, and lower leg muscles. Calf hypertrophy has also been reported in some cases. LGMD2L progresses slowly, with most patients remaining ambulatory until late adulthood.

1591
(51.6%)

GNE myopathy

Facial palsy Scapular winging Shoulder girdle muscle weakness Weakness of long finger extensor muscles

Autosomal dominant inheritance Autosomal recessive inheritance

GNE myopathy is a rare autosomal recessive distal myopathy characterized by early adult-onset, slowly to moderately progressive distal muscle weakness that preferentially affects the tibialis anterior muscle and that usually spares the quadriceps femoris. Muscle biopsy reveals presence of rimmed vacuoles.

1591
(51.6%)

MYH7-related late-onset scapuloperoneal muscular dystrophy

Hand muscle weakness Hyperlordosis Myopathic facies Shoulder girdle muscle weakness

X-linked recessive inheritance

1591
(51.6%)

Autosomal recessive progressive external ophthalmoplegia

Hand muscle weakness Mask-like facies Scapular winging

1591
(51.6%)

Gastrointestinal stromal tumor

Back pain Palmar hyperkeratosis Periorbital edema

Autosomal dominant inheritance Sporadic

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, typically presenting in adults over the age of 40 (mean age 63), and only rarely in children, in various regions of the GI tract, most commonly the stomach or small intestine but also less commonly in the esophagus, appendix, rectum and colon. GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass, blood in stool, and intestinal obstruction. GISTs can also be seen in familial syndromes such as Carney triad and neurofibromatosis type 1.

1597
(51.5%)

Autosomal recessive spastic paraplegia type 53

Microcephaly Upper limb hypertonia

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 53 (SPG53) is a very rare, complex type of hereditary spastic paraplegia characterized by early-onset spastic paraplegia (with spasticity in the lower extremities that progresses to the upper extremities) associated with developmental and motor delay, mild to moderate cognitive and speech delay, skeletal dysmorphism (e.g. kyphosis and pectus), hypertrichosis and mildly impaired vibration sense. SPG53 is due to mutations in the VPS37A gene (8p22) encoding vacuolar protein sorting-associated protein 37A.

1597
(51.5%)

Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome

Macrocephaly Upper limb asymmetry

Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome is a rare, genetic, polymalformative syndrome characterized by progressive, proportionate, asymmetric segmental overgrowth (with soft tissue hypertrophy and ballooning effect) that develops and progresses rapidly in early childhood, arteriovenous and lymphatic vascular malformations, lipomatosis and linear epidermal nevus (arranged in whorls along the lines of Blaschko). Clinical symptoms of Cowden syndrome, such as macrocephaly and progressive development of numerous hypertrophic hamartomatous and neoplastic lesions involving multiple organs and systems, are also associated. Patients present an increased risk of developing cancer.

1597
(51.5%)

Autosomal recessive limb-girdle muscular dystrophy type 2T

Distal upper limb muscle weakness Microcephaly

Autosomal recessive inheritance

A form of limb-girdle muscular dystrophy, that can present from birth to early childhood, characterized by hypotonia, microcephaly, mild proximal muscle weakness (leading to delayed walking and difficulty climbing stairs), mild intellectual disability and epilepsy. Additional manifestations reported in some patients include cataracts, nystagmus, cardiomyopathy, and respiratory insufficiency.

1597
(51.5%)

Autosomal dominant centronuclear myopathy

Macrocephaly at birth Proximal muscle weakness in upper limbs

Autosomal dominant inheritance

A rare, inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy.