1300
(57.0%)

Alpha-mannosidosis

Bowing of the long bones Macroglossia Mandibular prognathia

Autosomal recessive inheritance

An inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual deficit.

1300
(57.0%)

Autosomal recessive malignant osteopetrosis

Abnormality of the metaphysis Delayed eruption of teeth Mandibular osteomyelitis

Infantile malignant osteopetrosis is a rare congenital disorder of bone resorption characterised by generalised skeletal densification.

1300
(57.0%)

McCune-Albright syndrome

Abnormality of the dentition Mandibular prognathia Metaphyseal chondrodysplasia

Somatic mosaicism

McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP).

1304
(57.0%)

Sclerosteosis

Abnormality of the nose Craniofacial hyperostosis Curved distal phalanges of the hand Diaphyseal thickening

Sclerosteosis is a very rare serious sclerosing hyperostosis syndrome characterized clinically by variable syndactyly and progressive skeletal overgrowth (particularly of the skull), resulting in distinctive facial features (mandibular overgrowth, frontal bossing, midfacial hypoplasia), cranial nerve entrapment causing facial palsy and deafness, and potentially lethal elevation of intracranial pressure.

1305
(57.0%)

Non-eruption of teeth-maxillary hypoplasia-genu valgum syndrome

Genu valgum Hypodontia Malar flattening Maxillozygomatic hypoplasia

Autosomal recessive inheritance

Noneruption of teeth - maxillary hypoplasia - genu valgum is an extremely rare syndrome that is characterized by multiple unerupted permanent teeth, hypoplasia of the alveolar process and of the maxillo-zygomatic region, severe genu valgum and deformed ears.

1306
(57.0%)

Isolated arrhinia

Absent nasal septal cartilage Eyelid coloboma Underdeveloped nasal alae

An extremely rare, major congenital malformation consisting of an absence of the nose ranging from hyporrhinia (absence of external nasal structures) to total arrhinia (absence of external nose, nasal airways, olfactory bulbs, or olfactory nerve) often causing respiratory distress and requiring surgical correction. Arrhinia can be bilateral or unilateral (hemiarrhinia). Associated anomalies include ocular features (hypertelorism, microphthalmia, eyelid coloboma), facial clefts, midline defects and microtia.

1307
(57.0%)

Episodic ataxia type 1

Craniofacial disproportion Hand clenching Scoliosis

Autosomal dominant inheritance

Episodic ataxia type 1 (EA1) is a frequent form of Hereditary episodic ataxia (EA; see this term) characterized by brief episodes of ataxia, neuromyotonia, and continuous interictal myokymia.

1308
(57.0%)

Maternal uniparental disomy of chromosome 6

Cleft palate Cleft upper lip Slender long bone

Maternal uniparental disomy of chromosome 6 is an uniparental disomy of maternal origin characterized by intrauterine growth retardation. Homozygosity for a recessive disease mutation for which only a mother is a carrier may lead to other phenotypes.

1309
(57.0%)

Woolly hair-hypotrichosis-everted lower lip-outstanding ears syndrome

Abnormality of the dentition Aplasia/Hypoplasia of the eyebrow Delayed skeletal maturation Everted lower lip vermilion

1310
(57.0%)

Ulnar hemimelia

Osteomyelitis Radial bowing

Ulnar hemimelia is a congenital ulnar deficiency of the forearm characterized by complete or partial absence of the ulna bone.

1311
(56.9%)

Undetermined early-onset epileptic encephalopathy

Downslanted palpebral fissures Hypodontia Limb hypertonia Microcephaly

1312
(56.9%)

Cooks syndrome

Brachydactyly Broad thumb

Autosomal dominant inheritance

Cooks syndrome is a malformation syndrome affecting the apical structures of digits and presenting with hypo/aplasia of nails and distal phalanges. More than half of digits are usually involved and the thumbs may appear digitalized.

1313
(56.9%)

CINCA syndrome

Brachydactyly Frontal bossing Macrocephaly Metaphyseal dysplasia

Autosomal dominant inheritance

Chronic Infantile Neurological, Cutaneous, and Articular (CINCA) syndrome is characterised by skin rash, joint involvement, chronic meningitis with granulocytes and, in some cases, sensorineural hearing loss and ocular signs.

1314
(56.8%)

Congenital vertical talus

Arachnodactyly Downslanted palpebral fissures Scoliosis Triangular face

Autosomal dominant inheritance

Isolated congenital vertical talus (CVT) is a rare pedal deformity recognizable at birth by a dislocation of the talonavicular joint, resulting in a characteristic radiographic near-vertical orientation of the talus.

1314
(56.8%)

Bazex-Dupré-Christol syndrome

Abnormal clavicle morphology Abnormality of finger Sparse and thin eyebrow Sparse or absent eyelashes

X-linked dominant inheritance

Bazex-Dupré-Christol syndrome is a rare genodermatosis with a predisposition to early-onset basal cell carcinomas.

1314
(56.8%)

Leiomyosarcoma

Back pain Ectropion Facial asymmetry Finger swelling

1317
(56.8%)

Gordon syndrome

Cleft palate Clinodactyly of the 5th finger Pectus excavatum

Autosomal dominant inheritance

Gordon syndrome, also known as distal arthrogryposis type 3, is an extremely rare multiple congenital malformation syndrome characterized by congenital contractures of hand and feet with variable degrees of severity of camptodactyly, clubfoot and, less frequently, cleft palate. Intelligence is normal but in some cases, additional abnormalities, such as short stature, kyphoscoliosis, ptosis, micrognathia, and cryptorchidism may also be present. Gordon syndrome, Marden-Walker syndrome and arthrogryposis with oculomotor limitation and electroretinal anomalies clinically and genetically overlap, and could represent variable expressions of the same condition.

1318
(56.8%)

Thymic carcinoma

Back pain Clubbing Palpebral edema Stomatitis

Thymic carcinoma (TC) is a type of thymic epithelial neoplasm (see this term) characterized by a high malignant potential.

1318
(56.8%)

Primary biliary cholangitis

Chest pain Clubbing Parotitis Xanthelasma

Primary biliary cholangitis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure.

1320
(56.8%)

X-linked intellectual disability, Van Esch type

Clinodactyly of the 5th finger Microcephaly Retrognathia

X-linked intellectual deficit, Van Esch type is characterized by mild to moderate intellectual deficit associated with low birth weight, short stature, microcephaly and variable hypergonadotropic hypogonadism.

1320
(56.8%)

Psoriasis-related juvenile idiopathic arthritis

Abnormality of the temporomandibular joint Abnormality of the wrist Finger dactylitis

Juvenile psoriatic arthritis is a relatively rare form of juvenile idiopathic arthritis (JIA) representing less than 10% of all JIA cases.

1322
(56.7%)

Autosomal dominant epidermolytic ichthyosis

Brachydactyly Conjunctival hamartoma Palmoplantar hyperkeratosis

Autosomal dominant inheritance Autosomal recessive inheritance

Epidermolytic ichthyosis (EI) is a rare keratinopathic ichthyosis (KPI; see this term), that is characterized by a blistering phenotype at birth which progressively becomes hyperkeratotic.

1323
(56.7%)

Dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome

Cone-shaped epiphysis Platyspondyly Short philtrum

Dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome is characterised by the association of dentinogenesis imperfecta, delayed tooth eruption, facial dysmorphology, small stature, sensorineural hearing loss and mild intellectual deficit. It has been described in two brothers born to consanguineous parents. Transmission is autosomal recessive.

1324
(56.6%)

Autosomal recessive spastic paraplegia type 77

Hip dysplasia Macrodontia of permanent maxillary central incisor Retrognathia

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 77 is a rare, pure or complex hereditary spastic paraplegia characterized by an infancy to childhood onset of slowly progressive lower limb spasticity, delayed motor milestones, gait disturbances, hyperreflexia and various muscle abnormalities, including weakness, hypotonia, intention tremor and amyotrophy. Ocular abnormalities (e.g. strabismus, ptosis) and other neurological abnormalities, such as dysarthria, seizures and extensor plantar responses, may also be associated.

1324
(56.6%)

SAPHO syndrome

Abnormality of the sacroiliac joint Mandibular osteomyelitis Periodontitis

A rare, pyogenic autoinflammatory disease, characterized by the association of neutrophilic cutaneous involvement and chronic nonbacterial osteomyelitis.

1326
(56.6%)

Cyclic neutropenia

Cheilitis Oral ulcer Overlapping toe

Autosomal dominant inheritance

1327
(56.6%)

Griscelli syndrome

Abnormal eyelash morphology Encephalocele Femur fracture

Griscelli syndrome (GS) is a rare cutaneous disease characterized by a silvery-gray sheen of the hair and hypopigmentation of the skin, which can be associated to primary neurological impairment (type 1), immunologic impairment (type 2) or be isolated (type 3).

1328
(56.6%)

Autosomal recessive cutis laxa type 2A

Downslanted palpebral fissures Long philtrum

A rare, genetic, dermis elastic tissue disease characterized by redundant, overfolded skin of variable severity, ranging from wrinkly skin to cutis laxa associated with pre- and post-natal growth retardation, hypotonia, mild to moderate developmental delay, late closure of anterior fontanelle, and craniofacial dysmorphism (including microcephaly, hypertelorism, downslanting palpebral fissures, large, prominent nasal root with funnel nose, small, low-set ears, long philtrum, drooping facial skin). Additional manifestations may include seizures, intellectual disability, congenital hip dislocation, inguinal hernia, and cortical and cerebellar malformations. Pretibial pseudo-ecchymotic skin lesions have occasionally been associated.

1328
(56.6%)

Fetal valproate syndrome

Epicanthus Long philtrum Narrow mouth

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

1328
(56.6%)

Delayed speech-facial asymmetry-strabismus-ear lobe creases syndrome

Downslanted palpebral fissures High palate Long philtrum

Autosomal dominant inheritance

This syndrome is extremely rare and is characterized by delayed speech development, mild facial asymmetry, strabismus and transverse ear lobe creases.

1328
(56.6%)

Deaf blind hypopigmentation syndrome, Yemenite type

Abnormal size of the palpebral fissures Short philtrum

Autosomal recessive inheritance

Yemenite deaf-blind hypopigmentation syndrome is an exceedingly rare genetic disorder characterized by cutaneous pigmentation anomalies, ocular disorders and hearing loss.

1332
(56.5%)

Isolated cleft lip

Non-midline cleft lip Talipes equinovarus Velopharyngeal insufficiency

Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base.

1333
(56.5%)

Endosteal hyperostosis, Worth type

Diaphyseal thickening Mandibular prognathia Torus palatinus

Autosomal dominant inheritance

Worth type autosomal dominant osteosclerosis is a sclerozing bone disorder characterized by generalized skeletal densification, particularly of the cranial vault and tubular long bones, which is not associated to an increased risk of fracture.

1333
(56.5%)

Gaucher disease

Fractures of the long bones Gingival bleeding Trismus

Gaucher disease (GD) is a lysosomal storage disorder encompassing three main forms (types 1, 2 and 3), a fetal form and a variant with cardiac involvement (Gaucher disease - ophthalmoplegia - cardiovascular calcification or Gaucher-like disease).

1333
(56.5%)

Chondrosarcoma

Diastema Epiphyseal dysplasia Epistaxis Trismus

Autosomal recessive inheritance

Chondrosarcoma is a malignant bone tumor arising from cartilaginous tissue, most frequently occuring at the ends of the femur and tibia, the proximal end of the humerus and the pelvis; and presenting with a palpable mass and progressive pain. Chondrosarcoma is usually slow growing at low histological grades and can be well managed by intralesional curettage or en-block wide resection.

1336
(56.5%)

Preeclampsia

Facial paralysis Narrow jaw Postaxial polydactyly

Preeclampsia is a hypertensive disorder of pregnancy that is characterized by new-onset hypertension with proteinuria presenting after 20 weeks of gestation, and depending on mild or severe forms may initially present with severe headache, visual disturbances, and hyperreflexia.

1337
(56.4%)

Dysspondyloenchondromatosis

Abnormality of ulnar metaphysis Platyspondyly

Dysspondyloenchondromatosis is a rare skeletal dysplasia characterized by anisospondyly and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.

1338
(56.4%)

Solitary bone cyst

Abnormal parietal bone morphology Abnormality of the humeral diaphysis

A benign non-epithelial bone cavity that is asymptomatic and that is found most commonly in the second decade of life by chance. The long bones are most often affected, but cases involving the jaw bone have been reported.

1339
(56.4%)

Dermatoosteolysis, Kirghizian type

Abnormal diaphysis morphology Abnormality of the dentition Brachydactyly Scoliosis

Autosomal recessive inheritance

Dermatoosteolysis, Kirghizian type, is characterised by recurrent skin ulceration, arthralgia, fever, peri-articular osteolysis, oligodontia and nail dystrophy. This disease has been described in five sibs in a family of Kirghizian origin (Central Asia). Three of the sibs also presented with keratitis leading to visual impairment or blindess. Transmission is autosomal recessive.

1340
(56.4%)

Alopecia universalis

Absent eyelashes Metaphyseal chondrodysplasia Microcephaly

Autosomal recessive inheritance

A disorder of most severe form of alopecia areata, an inflammatory disease of the hair follicle, which is characterized by a complete loss of hair of the scalp and all the hair-bearing areas of the body.

1341
(56.4%)

Opitz G/BBB syndrome

Cleft lip Epicanthus Large fontanelles

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

1342
(56.3%)

Van den Ende-Gupta syndrome

Arachnodactyly Blepharophimosis Convex nasal ridge

Autosomal recessive inheritance

Van den Ende-Gupta syndrome is a very rare syndrome characterized by blepharophimosis, arachnodactyly, joint contractures, and characteristic dysmorphic features.

1343
(56.3%)

Kufor-Rakeb syndrome

Abnormality of finger Blepharospasm Difficulty in tongue movements

Autosomal recessive inheritance

Kufor-Rakeb syndrome (KRS) is a rare genetic neurodegenerative disorder characterized by juvenile Parkinsonism, pyramidal degeneration (dystonia), supranuclear palsy, and cognitive impairment.

1344
(56.3%)

Hyperostosis corticalis generalisata

Diaphyseal thickening Mandibular prognathia Syndactyly

Autosomal recessive inheritance

Hyperostosis corticalis generalisata, also known as van Buchem disease, is a rare craniotubular hyperostosis characterized by hyperostosis of the skull, mandible, clavicles, ribs and diaphyses of the long bones, as well as the tubular bones of the hands and feet. Clinical manifestations include increased skull thickness with cranial nerve entrapment causing inconsistent cranial nerve palsies.

1345
(56.2%)

Epiblepharon

Clinodactyly Epicanthus Hypodontia Xerostomia

1346
(56.2%)

Familial benign copper deficiency

Deep philtrum Diaphyseal thickening Wide nasal bridge

Familial benign copper deficiency is a rare disorder of mineral absorption and transport characterized by hypocupremia that manifests as failure to thrive, mild anemia, repeated seizures, hypotonia, and seborrheic skin. Spurring of the femur and tibia are also noted on radiographic imaging. Symptoms are reversible or improve with supplements of oral copper. There have been no further descriptions in the literature since 1988.

1347
(56.1%)

Nasal dermoid cyst

Bifid tongue Encephalocele Recurrent sinusitis Unilateral cleft lip

Autosomal dominant inheritance

1347
(56.1%)

Supernumerary nostril

Abnormality of ethmoid sinus Abnormality of the face Osteoma Unilateral cleft lip

Supernumerary nostril is an extremely rare congenital malformation characterized by the presence of one or more accessory nostrils, with or without accessory cartilage, located medially, above, below or laterally to the other nostrils. Unlike in polyrhinia (see this term) there is no duplication of the nasal septum/cavity. Supernumerary nostril is often associated with other congenital malformations usually of face.

1349
(56.1%)

Actinomycosis

Clubbing Periodontitis Sinusitis

1350
(56.1%)

Autosomal dominant prognathism

Everted lower lip vermilion Mandibular prognathia

Autosomal dominant inheritance

A rare, genetic, developmental defect during embryogenesis disorder characterized by abnormal forward projection of the mandible beyond the standard relation to the cranial base, with lower incisors often overlapping the upper incisors, that is inherited in an autosomal dominant manner. Association with mildly everted lower eyelids, flat malar area, thickened lower lip and craniosynostosis has been reported.

1350
(56.1%)

Oral submucous fibrosis

Cheilitis Narrow mouth Trismus

Oral submucous fibrosis (OSMF) is a chronic, progressive disease that alters the fibroelasticity of the oral submucosa, prevalent in India and Southeast Asia but rare elsewhere, and characterized by burning and pain in the oral cavity, loss of gustatory sensation, the presence of blanched fibrous bands and stiffening of the oral mucosa and oro-pharynx (leading to trismus and a progressive reduction in mouth opening) and an increased risk of developing oral squamous cell cancer (3-19%). It is usually associated with the chewing of the areca nut (an ingredient in betel quid) but the exact etiology is unknown and there is currently no effective treatment.

1352
(55.9%)

Trisomy Xq28

Epicanthus Pectus excavatum Tented upper lip vermilion

X-linked recessive inheritance

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

1352
(55.9%)

Omphalocele syndrome, Shprintzen-Goldberg type

Downslanted palpebral fissures Scoliosis Thin upper lip vermilion

Autosomal dominant inheritance

Shprintzen–Goldberg omphalocele syndrome is a very rare inherited malformation syndrome characterized by omphalocele, scoliosis, mild dysmorphic features (downslanted palpebral fissures, s-shaped eyelids and thin upper lip), laryngeal and pharyngeal hypoplasia and learning disabilities.

1354
(55.8%)

Otoonychoperoneal syndrome

Abnormal diaphysis morphology Dolichocephaly Upslanted palpebral fissure

Autosomal recessive inheritance

1355
(55.8%)

Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

Clinodactyly of the 5th finger Hip dysplasia Radioulnar synostosis Sensorineural hearing impairment

Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome is characterised by the association of proximal fusion of the radius and ulna with congenital amegakaryocytic thrombocytopaenia. Less than 10 cases have been reported in the literature so far. The syndrome is transmitted as an autosomal dominant trait and is caused by mutations in the HOXA11 gene (7p15).

1356
(55.8%)

Anonychia-microcephaly syndrome

Abnormality of the dentition Clinodactyly of the 5th finger Microcephaly

A multiple congenital anomaly disorder characterized by anonychia congenita totalis and microcephaly, and normal intelligence along with some minor anomalies including single transverse palmar creases, fifth-finger clinodactyly and widely-spaced teeth.

1356
(55.8%)

Hydrocephaly-tall stature-joint laxity syndrome

Arachnodactyly Frontal bossing High, narrow palate

Autosomal recessive inheritance

Hydrocephaly-tall stature-joint laxity syndrome is a multiple congenital anomalies syndrome described in two sisters and characterized by the presence of hydrocephalus (onset in infancy), tall stature, joint laxity, and thoracolumbar kyphosis. There have been no further descriptions in the literature since 1989.

1356
(55.8%)

Microcephaly-cardiomyopathy syndrome

Clinodactyly of the 5th finger High, narrow palate Microcephaly Sloping forehead

Autosomal recessive inheritance

Microcephaly-cardiomyopathy syndrome is characterised by severe intellectual deficit, microcephaly and dilated cardiomyopathy. Hand and foot anomalies have also been reported. The syndrome has been described in three individuals. Transmission is autosomal recessive.

1356
(55.8%)

Cryptorchidism-arachnodactyly-intellectual disability syndrome

Abnormality of the dentition Arachnodactyly Dolichocephaly

Cryptorchidism-arachnodactyly-intellectual disability syndrome is a rare, multiple congenital anomalies syndrome characterized by psychomotor delay, severe intellectual deficit, severe muscle hypoplasia (with absence of subcutaneous fatty tissue), generalized contractures, craniofacial dysmorphic features (dolichocephaly, esotropia, ears of unequal size, high palate), chest and spinal deformities (i.e. sternum shifted to side, kyphoscoliosis), pulmonary anomalies (unilateral hypoplastic bronchial system), arachnodactyly, and genital abnormalities (cryptorchidism, hypospadias, testicular agenesis). Repeated respiratory tract infections and atelectasis are also associated. There have been no further descriptions in the literature since 1970.

1356
(55.8%)

Sagliker syndrome

Abnormality of finger Abnormality of the dentition Frontal bossing

1356
(55.8%)

Tricho-dento-osseous syndrome

Abnormality of the mastoid Finger clinodactyly Taurodontia

Autosomal dominant inheritance

Tricho-dento-osseous dysplasia (TDO) belongs to the ectodermal dysplasias and is characterised by curly/kinky hair at birth, enamel hypoplasia with discolouration and molar taurodontism, increased overall bone mineral density (BMD) and increased thickness of the cortical bones of the skull.

1356
(55.8%)

Bangstad syndrome

Abnormality of the dentition Deviation of finger Microcephaly

Autosomal recessive inheritance

Bangstad syndrome is a rare endocrine disease characterized by the association of primordial birdheaded nanism, progressive ataxia, goiter, primary gonadal insufficiency and insulin resistant diabetes mellitus. Plasma concentrations of TSH, PTH, LH, FSH, ACTH, glucagon, and insulin are usually elevated. A generalized cell membrane defect was suggested to be the pathophysiological abnormality in these patients. The mode of inheritance was thought to be autosomal recessive. There have been no further descriptions in the literature since 1989.

1356
(55.8%)

Microphthalmia with brain and digit anomalies

High palate Microcephaly Proximal placement of thumb

Autosomal dominant inheritance

Microphthalmia with brain and digit anomalies is characterised by anophthalmia or microphthalmia, retinal dystrophy, and/or myopia, associated in some cases with cerebral anomalies. It has been described in two families. Polydactyly may also be present. Linkage analysis allowed identification of mutations in the BMP4 gene, which has already been shown to play a role in eye development.

1356
(55.8%)

Trigonocephaly-short stature-developmental delay syndrome

Broad secondary alveolar ridge Fifth finger distal phalanx clinodactyly Small anterior fontanelle

X-linked recessive inheritance

Trigonocephaly-short stature-developmental delay syndrome is characterised by short stature, trigonocephaly and developmental delay. It has been described in three males. Moderate intellectual deficit was reported in one of the males and the other two patients displayed psychomotor retardation. X-linked transmission has been suggested but autosomal recessive inheritance can not be ruled out.

1356
(55.8%)

Harrod syndrome

Arachnodactyly Microcephaly Narrow mouth

Harrod syndrome is characterized by the association of intellectual deficit, facial dysmorphism (a highly arched palate, pointed chin, and small mouth, hypotelorism, a long nose and large protruding ears), arachnodactyly, hypogenitalism (undescended testes and hypospadias) and failure to thrive.

1356
(55.8%)

Ring chromosome 12 syndrome

Abnormal 5th finger morphology Abnormal facial shape High, narrow palate Microcephaly

Ring chromosome 12 syndrome is a rare chromosomal anomaly syndrome with a highly variable phenotype principally characterized by postnatal growth retardation, variable degrees of developmental delay and intellectual disability, microcephaly and facial dysmorphism (incl. epicanthal folds, low-set, cupped ears, prominent nose with flat nasal bridge, high arched palate, micrognathia). Skeletal abnormalities (e.g. pectus excavatum, clinodactyly), congenital heart malformations, cryptorchidism, café-au-lait spots and epilepsy have also been reported.

1356
(55.8%)

Megalencephaly-capillary malformation-polymicrogyria syndrome

Hand polydactyly Macrocephaly Wide mouth

Somatic mutation Sporadic

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a polymalfomative syndrome characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations (most distinctively polymicrogyria), abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism.

1356
(55.8%)

Lhermitte-Duclos disease

Hand polydactyly Macrocephaly Macroglossia

A very rare disorder characterized by abnormal development and enlargement of the cerebellum, and an increased intracranial pressure.

1369
(55.7%)

Microcephaly-microcornea syndrome, Seemanova type

Brachycephaly Epicanthus Narrow mouth Retrognathia

Microcephaly-microcornea syndrome, Seemanova type is characterised by microcephaly and brachycephaly, eye anomalies (microphthalmia, microcornea, congenital cataract), hypogenitalism, severe intellectual deficit, growth retardation and progressive spasticity. It has been described in two patients (a male and his sister's son). Both patients also presented with facial dysmorphism, including upslanting palpebral fissures, epicanthal folds, highly arched palate, microstomia, and retrognathia. This syndrome is transmitted as an X-linked trait.

1369
(55.7%)

Dermoodontodysplasia

Abnormal eyelid morphology Hypodontia Mandibular prognathia

Autosomal dominant inheritance

Dermo-odonto dysplasia belongs to the group of tricho-odonto-onychial dysplasias. It is characterised by signs of variable severity: dry and thin skin, dental anomalies, nail alteration and trichodysplasia. Fourteen cases have been described so far. Autosomal dominant transmission is likely.

1371
(55.7%)

Congenital cystic eye

Cryptophthalmos Meningoencephalocele

1372
(55.6%)

Woolly hair

Hypodontia Palmoplantar hyperkeratosis Sparse lateral eyebrow

Woolly hair is a rare congenital abnormality of the structure of the scalp hair marked by extreme kinkiness of the hair.

1373
(55.6%)

Osteoblastoma

Jaw swelling Odontoma Sinusitis Telecanthus

A rare, neoplastic disease characterized by a typically benign, locally aggressive, non self-limiting, osteoblastic bone tumor, usually located on the spine, proximal humerus and hip (although any bone may be involved), generally manifesting with slowly progressive, dull aching pain which is difficult to localize and is not relieved by nonsteroidal anti-inflammatory drugs or aspirin. Neurologic symptoms, such as cranial nerve palsies, myelopathy, neuralgia, radiculopathy, paraparesis or paraplegia, may be associated if the spine is involved. Imaging reveals a lytic (or mixed lytic and blastic) lesion with a radiolucent nidus (> 2 cm) associated with reactive sclerotic bone.

1373
(55.6%)

Dyskeratosis congenita

Abnormality of the dentition Blepharitis Hypoplasia of the maxilla Microcephaly

Dyskeratosis congenita (DC) is a rare ectodermal dysplasia that often presents with the classic triad of nail dysplasia, skin pigmentary changes, and oral leukoplakia associated with a high risk of bone marrow failure (BMF) and cancer.

1375
(55.6%)

Distal symphalangism

Brachydactyly Microdontia Scoliosis Synostosis of carpal bones

Autosomal dominant inheritance

Distal symphalangism is a very rare bone disorder characterized by ankylosis of the distal interphalangeal joints of the hands and/or feet.

1376
(55.6%)

Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome

Absent eyelashes Palmar telangiectasia

Hypotrichosis - lymphedema - telangiectasia is an extremely rare syndromic lymphedema disorder characterized by early-onset hypotrichosis, childhood-onset lymphedema, and variable telangiectasia, particularly of the palms.

1376
(55.6%)

Juvenile dermatomyositis

Palmoplantar hyperkeratosis Palpebral edema Periorbital edema

Autosomal dominant inheritance

Juvenile dermatomyositis (JDM) is the early-onset form of dermatomyositis (DM, see this term), a systemic, autoimmune inflammatory muscle disorder, characterized by proximal muscle weakness, evocative skin lesion, and systemic manifestations.

1378
(55.5%)

Barber-Say syndrome

Ablepharon Shawl scrotum Wide mouth

Autosomal dominant inheritance Autosomal recessive inheritance

Barber Say syndrome (BSS) is a rare ectodermal dysplasia with neonatal onset characterized by congenital generalized hypertrichosis, atrophic skin, ectropion and microstomia.

1379
(55.5%)

Tyrosinemia type 2

Malar flattening Palmoplantar hyperkeratosis

Autosomal recessive inheritance

Tyrosinemia type 2 is an inborn error of tyrosine metabolism characterized by hypertyrosinemia with oculocutaneous manifestations and, in some cases, intellectual deficit.

1380
(55.4%)

Colobomatous microphthalmia

Microcephaly Orbital cyst Preaxial polydactyly

Colobomatous microphthalmia is a developmental disorder of the eye characterized by unilateral or bilateral microphthalmia associated with ocular coloboma.

1381
(55.4%)

Bronchogenic cyst

Cleft lip Cleft mandible Pectus excavatum

Bronchogenic cysts (BCs) are congenital malformations resulting from abnormal budding of the foregut and are most commonly found in the mediastinum.

1382
(55.3%)

Familial adenomatous polyposis

Abnormality of the maxilla Cleft lip Delayed eruption of teeth

Familial adenomatous polyposis (FAP) is characterized by the development of hundreds to thousands of adenomas in the rectum and colon during the second decade of life.

1383
(55.3%)

Kawasaki disease

Cheilitis Conjunctivitis Mastoiditis

Multifactorial inheritance

Kawasaki disease (KD) is a febrile, systemic, self-limiting vasculitis affecting children and characterized by inflammation in the medium sized vessels associated with coronary arterial aneurysms (CAA) that may be life threatening when untreated. KD is the most common cause of acquired heart disease in children in developed countries and is a risk factor for ischemic heart disease in adulthood.

1384
(55.3%)

Neuralgic amyotrophy

Cleft palate Narrow mouth Scapular winging Sprengel anomaly

Neuralgic amyotrophy (NA) is an uncommon disorder of the peripheral nervous system characterized by the sudden onset of extreme pain in the upper extremity followed by rapid multifocal motor weakness and atrophy and a slow recovery in months to years. NA includes both an idiopathic (INA, also known as Parsonage-Turner syndrome) and hereditary (HNA) form.

1385
(55.2%)

Intermediate osteopetrosis

Abnormality of the dentition Erlenmeyer flask deformity of the femurs Osteosclerosis of the base of the skull

Autosomal recessive inheritance

Intermediate osteopetrosis is a rare, genetic primary bone dysplasia with increased bone density characterized by susceptibility to fractures after minor trauma, anemia, and characteristic skeletal radiographic changes, such as sandwich vertebra, bone-within-bone appearance, Erlenmeyer-shaped femoral metaphysis, and mild osteosclerosis of the skull base. Dental anomalies and visual impairment secondary to optic nerve compression have been rarely described.

1386
(55.1%)

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

Brachycephaly Malar flattening Narrow mouth Thin upper lip vermilion

Autosomal dominant inheritance

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome is a rare, genetic, syndromic intellecutal disability disorder characterized by craniofacial dysmorphism (microcephaly, hypotonic facies, strabismus, long and flat malar region, posteriorly rotated ears, flat nasal bridge with broad nasal tip, short philtrum, thin vermillion border, open mouth with down-turned corners, high arched palate, pointed chin), global developmental delay, intellectual disability and variable neurobehavioral abnormalities (autism spectrum disorder, aggressivness, self injury). Additional features include vision abnormalities and variable sensorineural hearing loss, as well as short stature, hypotonia and gastrointestinal manifestations (e.g. poor feeding, gastroesophageal reflux, constipation).

1387
(55.1%)

Trichodermodysplasia-dental alterations syndrome

Abnormality of the hip bone Delayed eruption of teeth Scoliosis Sparse or absent eyelashes

Trichodermodysplasia-dental alterations syndrome is a rare, genetic ectodermal dysplasia syndrome characterized by sparse, thin, brittle scalp hair, as well as sparse eyebrows, eyelashes, axillary and pubic hair, delayed eruption of deciduous teeth and hypodontia of both dentitions. Mild palmoplantar keratosis, café-au-lait spots on back, mild dystrophy of nails, and tibial deflection of toes are also associated. There have been no further descriptions in the literature since 1986.

1388
(55.1%)

Autosomal recessive complex spastic paraplegia due to Kennedy pathway dysfunction

Ankle clonus Cleft palate Microcephaly

1388
(55.1%)

Global developmental delay-neuro-ophthalmological abnormalities-seizures-intellectual disability syndrome

Cleft palate Limb hypertonia Microcephaly

1388
(55.1%)

Kallmann syndrome

Cleft palate Dandy-Walker malformation Pes cavus

Kallmann syndrome (KS) is a developmental genetic disorder characterized by the association of congenital hypogonadotropic hypogonadism (CHH) due to gonadotropin-releasing hormone (GnRH) deficiency, and anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs).

1388
(55.1%)

Walker-Warburg syndrome

Cleft palate Metatarsus valgus Microcephaly

Walker-Warburg Syndrome (WWS) is a rare form of congenital muscular dystrophy associated with brain and eye abnormalities.

1392
(55.1%)

Reactive arthritis

Atlantoaxial instability Clubbing Conjunctivitis Periodontitis

Reactive arthritis (ReA) is an autoimmune disorder belonging to the group of seronegative spondyloarthropathies and is characterized by the classic triad of arthritis, urethritis and conjunctivitis.

1393
(55.1%)

Craniofacial conodysplasia

Abnormality of the face Cone-shaped epiphyses of the phalanges of the hand Craniofacial dysostosis

Craniofacial conodysplasia is characterised by craniofacial dysplasia, cone-shaped physes of the hands and feet, and neurological manifestations resembling cerebral palsy. It has been described in one family. The syndrome appeared to be transmitted as a dominant trait.

1394
(55.0%)

Geroderma osteodysplastica

Abnormality of epiphysis morphology Hip dislocation Malar flattening Mandibular prognathia

Autosomal recessive inheritance

Geroderma osteodysplastica (GO) is characterized by lax and wrinkled skin (especially on the dorsum of the hands and feet and abdomen), progeroid features, hip dislocation, joint laxity, severe short stature/dwarfism, severe osteoporosis, vertebral abnormalities and spontaneous fractures, and developmental delay and mild intellectual deficit.

1395
(55.0%)

Autosomal recessive hypophosphatemic rickets

Craniosynostosis Delayed eruption of teeth Enlargement of the wrists Genu varum

A rare hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia and slow growth.

1395
(55.0%)

Hypocalcemic vitamin D-dependent rickets

Delayed epiphyseal ossification Delayed eruption of teeth Enlargement of the wrists Frontal bossing

Hypocalcemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate hypophosphatemia.

1397
(55.0%)

X-linked intellectual disability, Shashi type

Blepharophimosis Everted lower lip vermilion Macroorchidism

X-linked recessive inheritance

X-linked intellectual disability, Shashi type is characterised by moderate intellectual deficit, obesity, macroorchidism and a characteristic facies (large ears, a prominent lower lip and puffy eyelids). It has been described in nine boys from two families. Transmission is X-linked and the causative gene has been localised to the q21.3-q27 region of the X chromosome.

1397
(55.0%)

Ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome

Eclabion Ectropion Hypogonadism

Autosomal recessive inheritance

Ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome is an ectodermal dysplasia syndrome characterized by severe generalized lamellar icthyosis at birth with alopecia, eclabium, ectropion and intellectual disability. Although similar to Sjögren-Larsson syndrome, this syndrome lacks the presence of neurologic or macular changes. There have been no further descriptions in the literature since 1987.

1397
(55.0%)

Acrodermatitis enteropathica

Abnormal eyelid morphology Abnormality of the tongue Cheilitis

Autosomal recessive inheritance

A rare inherited inborn error of metabolism resulting in a severe zinc deficiency and characterized by acral dermatitis, alopecia, diarrhea and growth failure.

1400
(55.0%)

ANE syndrome

Hypodontia Microcephaly Ulnar deviation of the hand

Autosomal recessive inheritance

A rare, genetic, neuro-endocrino-cutaneous disorder characterized by highly variable degrees of alopecia, moderate to severe intellectual disability, progressive, late-onset motor deterioration and combined anterior pituitary hormone deficiency, manifesting with central hypogonadotropic hypogonadism, delayed or absent puberty, growth hormone deficiency (resulting in short stature), progressive central adrenal insufficiency and a hypoplastic anterior pituitary gland. Additional features include hypodontia, flexural reticulate hyperpigmentation, gynecomastia, microcephaly and kyphoscoliosis.