701
(66.8%)

Patent ductus arteriosus-bicuspid aortic valve-hand anomalies syndrome

Abnormal hand morphology Abnormality of the face Short 5th metacarpal

Autosomal dominant inheritance

Patent ductus arteriosus - bicuspid aortic valve - hand anomalies syndrome is a very rare heart-hand syndrome (see this term) that is characterized by a variety of cardiovascular anomalies including patent arterial duct, bicuspid aortic valve and pseudocoarctation of the aorta in conjunction with hand anomalies such as brachydactyly and ulnar ray derivative i.e. fifth metacarpal hypoplasia. Transmission is most likely autosomal dominant.

702
(66.8%)

Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome

Abnormality of fibula morphology Aplasia/Hypoplasia of the thumb Aplasia/Hypoplasia of the tibia

Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome is a rare, genetic dysostosis syndrome, with marked inter- and intra-familial variation, typically characterized by triphalangeal thumbs, hand and/or foot polysyndactyly and/or absent/hypoplastic tibiae (associated with duplication of fibulae in some cases), although isolated triphalangeal thumbs have also been reported. It is often accompanied with remarkable short stature and additional features may include radio-ulnar synostosis and hand oligodactyly, as well as abnormal carpal and metatarsal bones.

702
(66.8%)

Retiform hemangioendothelioma

Hemangioma Small finger

702
(66.8%)

Camptobrachydactyly

Aplasia/Hypoplasia of the thumb Septate vagina

Autosomal dominant inheritance

Camptobrachydactyly is an extremely rare brachydactyly syndrome, characterized by short broad hands and feet with brachydactyly associated with congenital flexion contractures of the proximal and/or distal interphalangeal joints of the fingers, as well as syndactyly of feet. Polydactyly, septate vagina and urinary incontinence were also occasionally reported. Camptobrachydactyly has been described in 18 members of 1 family, suggesting an autosomal dominant inheritance. There have been no further descriptions in the literature since 1972.

702
(66.8%)

DK1-CDG

Adactyly Dry skin

Autosomal recessive inheritance

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

702
(66.8%)

Diphallia

Absent thumb Inguinal hernia

A rare, non-syndromic, urogenital tract malformation characterized by complete or partial penile duplication, ranging from only glans duplication to the presence of two penis shafts with either one (i.e. bifid phallus) or two (i.e. true diphallia) corpora cavernosum in each. Additional anomalies, such as urethra duplication, an abnormal voiding pattern, hypo- or epispadias, bifid/ectopic scrotum, bladder exstrophy or duplication, are frequently associated, but it may also present as an isolated anomaly. In severe cases, pubic symphysis diastasis, imperforate or duplicated anus, colon/ rectosigmoidal duplication, inguinal hernia and vertebral anomalies may be observed.

702
(66.8%)

Pigmented villonodular synovitis

Hypertelorism Small finger

Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disorder of the synovial membrane primarily affecting young adults (with a peak age of onset in the second to fourth decade of life) characterized by proliferative, locally invasive tumor-like lesions, usually involving a single joint, tendon sheath or bursa (most commonly the joints of the knee and hip and rarely others such as the ankle, shoulder and temporomandibular joints). It presents with pain and limitation of motion along with swelling, heat and tenderness over the involved joint, eventually leading to arthritic degeneration and significant locomotor deficit, if left untreated. PVNS can recur in patients even after treatment.

708
(66.7%)

Short stature-advanced bone age-early-onset osteoarthritis syndrome

Midface retrusion Short thumb

A rare, primary bone dysplasia characterized by proportional short stature, early cessation of bone growth, accelerated skeletal maturation, variable presence of early-onset osteoarthritis and osteochondritis dissecans, and normal endocrine evaluation. The variable dysmorphic features include mild to relative macrocephaly, frontal bossing, midfacial hypoplasia, flat nasal bridge, brachydactyly, broad thumbs, and lordosis.

708
(66.7%)

Osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome

Frontal bossing Short distal phalanx of finger

Osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome is characterised by osteoporosis, macrocephalus, brachytelephalangy, and hyperextensibility of the joints. Congenital amaurosis and intellectual deficit have also been reported. This syndrome has been described in three members of one family.

708
(66.7%)

Keutel syndrome

Long face Short distal phalanx of finger

Autosomal recessive inheritance

Keutel syndrome is characterised by diffuse cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenoses and facial dysmorphism.

711
(66.7%)

Lethal recessive chondrodysplasia

Macroglossia Micrognathia Micromelia Short long bone

Lethal recessive chondrodysplasia is an extremely rare lethal form of chondrodysplasia characterized by severe micromelic dwarfism, short and incurved limbs with normal hands and feet, facial dysmorphism (disproportionately large skull, frontal prominence, slightly flattened nasal bridge and short neck), muscular hypotonia, hyperlaxity of the extremities, and a narrow thorax. Most patients die of respiratory distress during the first hours or weeks of life. There have been no further descriptions in the literature since 1988.

712
(66.5%)

Ulna metaphyseal dysplasia syndrome

Abnormality of the dentition Abnormality of the ulna Aplasia/Hypoplasia of the radius

Autosomal dominant inheritance

Ulna metaphyseal dysplasia syndrome is a rare primary bone dysplasia characterized by dysplasia of the distal ulnar metaphyses, as well as metacarpal/metatarsal dysplasia and metaphyseal changes resembling enchondromata. Patients usually present bony swelling of the wrists with or without pain (knees and ankles may also be affected). Other variably associated features include platyspondyly, skeletal development delay, short stature and coxa valga.

712
(66.5%)

Camurati-Engelmann disease

Abnormality of the ulna Aplasia/Hypoplasia of the radius Carious teeth

Autosomal dominant inheritance

Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability. Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability.

714
(66.5%)

3q29 microduplication syndrome

Deep philtrum Downslanted palpebral fissures Large fontanelles Toe syndactyly

Autosomal dominant inheritance

3q29 microduplications are recently described chromosomal abnormalities with unclear clinical significance.

714
(66.5%)

Pyruvate dehydrogenase deficiency

Epicanthus Long philtrum Osteolytic defects of the middle phalanx of the 4th toe Trigonocephaly

Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders. Six subtypes related to the affected subunit of the PDH complex have been recognized with significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, and PDH phosphatase deficiency (see these terms).

714
(66.5%)

Okamoto syndrome

Long palpebral fissure Microcephaly Polydactyly Tented upper lip vermilion

Okamoto syndrome is characterised by congenital hydronephrosis, intellectual deficit, growth retardation, cleft palate, generalised hypotonia and a characteristic face. Cardiac anomalies have also been reported. To date, 6 cases have been reported.

717
(66.5%)

Dysmorphism-short stature-deafness-disorder of sex development syndrome

Cleft soft palate Highly arched eyebrow Micrognathia

Dysmorphism-short stature-deafness-disorder of sex development syndrome is characterized by dysmorphism (including facial asymmetry, arched eyebrows, hypertelorism, broad and flat nasal bridge, microtia, small nose with anteverted nostrils, micrognathia), deafness, cleft palate, male pseudohermaphroditism, and growth and psychomotor retardation. It has been described in two siblings. It is transmitted as an autosomal recessive trait.

718
(66.5%)

Hypoplastic tibiae-postaxial polydactyly syndrome

Aplasia/Hypoplasia of the thumb Depressed nasal tip Short tibia

Hypoplastic tibia-polydactyly syndrome is a very rare congenital malformation syndrome characterized by bilateral hypoplasia of the tibia with polydactyly of the feet and hands.

719
(66.5%)

Congenital fiber-type disproportion myopathy

Flexion contracture of finger High palate Micrognathia Tented upper lip vermilion

Autosomal dominant inheritance Autosomal recessive inheritance X-linked recessive inheritance Heterogeneous

A rare genetic, congenital, non-dystrophic myopathy characterized by neonatal or infantile-onset hypotonia and mild to severe generalized muscle weakness.

720
(66.5%)

Limb-mammary syndrome

Blepharitis Cleft lip Clinodactyly of the 5th finger Malar flattening

Autosomal dominant inheritance

Limb-mammary syndrome (LMS) is a rare disease belonging to the group of ectodermal dysplasias.

721
(66.5%)

Immune thrombocytopenic purpura

Absent radius Gingival bleeding

Autosomal dominant inheritance

Immune thrombocytopenic purpura (or immune thrombocytopenia; ITP) is an autoimmune coagulation disorder characterized by isolated thrombocytopenia (a platelet count <100,000/microL), in the absence of any underlying disorder that may be associated with thrombocytopenia.

722
(66.4%)

Jackson-Weiss syndrome

Abnormal palate morphology Mandibular prognathia Short metatarsal

Autosomal dominant inheritance

Jackson-Weiss syndrome (JWS) is a rare genetic disorder characterized by foot malformations (tarsal and metatarsal fusions; short, broad, medially deviated great toes) and in some patients craniosynostosis with facial anomalies. Hands are normal in affected patients.

723
(66.4%)

Brachydactyly-mesomelia-intellectual disability-heart defects syndrome

Abnormal palate morphology Brachydactyly Mesomelia Micrognathia

Brachydactyly-mesomelia-intellectual disability-heart defects syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by developmental delay, intellectual disability, thin habitus with narrow shoulders, mesomelic shortness of the arms, craniofacial dysmorphism (e.g. long lower face, maxillary hypoplasia, beak nose, short columella, prognathia, high arched palate, obtuse mandibular angle), brachydactyly (mostly involving middle phalanges) and cardiovascular anomalies (i.e. aortic root dilatation, mitral valve prolapse).

723
(66.4%)

Osteoglosphonic dysplasia

Brachydactyly Choanal atresia Micrognathia Multiple unerupted teeth Rhizomelia

Autosomal dominant inheritance

A rare disorder characterized by dwarfism, severe craniofacial abnormalities and multiple unerupted teeth.

725
(66.3%)

Craniofrontonasal dysplasia-Poland anomaly syndrome

Aplasia/Hypoplasia involving bones of the skull Sparse eyebrow Unilateral brachydactyly Wide mouth

Cranio-fronto-nasal dysplasia - Poland anomaly is a polymalformative syndrome characterised by craniosynostosis, Poland anomaly (see this term), cranio-fronto-nasal dysplasia, and genital and breast anomalies. Less than ten cases have been described so far.

726
(66.3%)

Camptodactyly of fingers

Brachydactyly Downslanted palpebral fissures Micrognathia Triangular face

Autosomal dominant inheritance

Camptodactyly of fingers is a rare, genetic, non-syndromic, congenital limb malformation disorder characterized by a painless, non-traumatic, non-neurogenic, often bilateral, permanent flexion contracture at the proximal interphalangeal joint of a postaxial finger, resulting in permanent volar inclination of the affected digit. The fifth finger is always involved, but additional digits might also be affected.

726
(66.3%)

Prominent glabella-microcephaly-hypogenitalism syndrome

Brachydactyly Micrognathia Prominent nasal bridge Short palpebral fissure

Autosomal recessive inheritance

Prominent glabella – microcephaly – hypogenitalism is a very rare syndrome described in two sibs and characterized by prenatal onset of growth deficiency, microcephaly, hypoplastic genitalia, and birth onset of convulsions.

728
(66.2%)

Silver-Russell syndrome

Clinodactyly of the 5th finger Micrognathia Thin vermilion border

Autosomal dominant inheritance Sporadic

Silver-Russell syndrome is characterized by growth retardation with antenatal onset, characteristic facies and limb asymmetry.

729
(66.2%)

Beemer-Ertbruggen syndrome

Bulbous nose Deep philtrum Micrognathia

Autosomal recessive inheritance

Beemer-Ertbruggen syndrome is a lethal malformation syndrome reported in 2 brothers of first-cousin parents that is characterized by hydrocephalus, cardiac malformation, dense bones, and unusual facies with down-slanting palpebral fissures, bulbous nose, broad nasal bridge, micrognathia and a long upper lip. There have been no further descriptions in the literature since 1984.

729
(66.2%)

3-hydroxyisobutyric aciduria

Long philtrum Micrognathia Triangular face

Autosomal recessive inheritance

3 hydroxyisobutyric aciduria is characterised by ketoacidotic episodes, cerebral anomalies and facial dysmorphism. It is an organic aciduria that involves valine metabolism. Thirteen cases have been described in the literature so far. Transmission is thought to be autosomal recessive.

729
(66.2%)

Polyvalvular heart disease syndrome

High palate Micrognathia Short philtrum

Polyvalvular heart disease syndrome is a recently described syndrome characterized by the combination of polyvalvular heart disease, short stature, facial anomalies and intellectual deficit.

729
(66.2%)

X-linked intellectual disability, Najm type

Broad forehead Long philtrum Micrognathia

X-linked dominant inheritance

Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development.

729
(66.2%)

Micro syndrome

High palate Micrognathia Short philtrum

Micro syndrome is an autosomal recessive disorder caracterised by ocular and neurodevelopmental defects and by microgenitalia. It presents with severe intellectual disability, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism.

734
(66.2%)

Tricho-retino-dento-digital syndrome

Abnormality of the dentition Short 5th metacarpal

Autosomal dominant inheritance

Tricho-retino-dento-digital syndrome is an autosomal dominant ectodermal dysplasia syndrome, characterized by uncombable hair syndrome (see this term), congenital hypotrichosis and dental abnormalities such as oligodontia (see this term) or hyperdontia, and associated with early-onset cataract, retinal pigmentary dystrophy, and brachydactyly with brachymetacarpia. Furthermore, hyperactivity and a mild intellectual deficit have been reported in affected patients.

734
(66.2%)

Hydrocephalus-obesity-hypogonadism syndrome

High, narrow palate Short 4th metacarpal

This syndrome is characterized by the association of congenital hydrocephalus, centripetal obesity, hypogonadism, intellectual deficit and short stature.

736
(66.2%)

Shprintzen-Goldberg syndrome

Abnormality of the metaphysis Arachnodactyly Downslanted palpebral fissures High, narrow palate Micrognathia

Autosomal dominant inheritance Sporadic

Shprintzen-Goldberg syndrome (SGS) is a very rare genetic disorder characterized by craniosynostosis, craniofacial and skeletal abnormalities, marfanoid habitus, cardiac anomalies, neurological abnormalities, and intellectual disability.

737
(66.1%)

Trisomy 5p

Abnormality of the metacarpal bones Epicanthus Micrognathia

Trisomy 5p is a chromosomal abnormality resulting from the duplication of a segment of variable size of the short arm of chromosome 5, which usually involves the distal band 5p15. The clinical presentation is variable but is always associated with severe intellectual deficit.

738
(66.1%)

MMEP syndrome

Mandibular prognathia Median cleft lip Triphalangeal thumb

The MMEP syndrome is a congenital syndromic form of split-hand/foot malformation (SHFM; see this term). It is characterized by microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. MMEP syndrome is considered to be a very rare condition, although the exact prevalence remains unknown. The etiology is not completely understood. Disruption of the sorting nexin 3 gene (SNX3; 6q21) has been shown to play a causative role in MMEP, although this was not confirmed in recent studies.

739
(66.1%)

Ring chromosome 1 syndrome

Clinodactyly of the 5th finger Downslanted palpebral fissures Long philtrum Microcephaly

Ring chromosome 1 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including significant intrauterine and postnatal growth failure, developmental delay, intellectual disability, microcephaly, and dysmorphic facial features. Some less frequent clinical features are dysgenesis of corpus callosum, atrial septal defect, rocker bottom feet and clinodactyly.

739
(66.1%)

White forelock with malformations

Clinodactyly of the 5th finger Deep philtrum Dolichocephaly Epicanthus

Autosomal recessive inheritance

White forelock with malformations is a multiple congenital anomalies syndrome characterized by poliosis, distinct facial features (epicanthal folds, hypertelorism, posterior rotation of ears, prominent philtrum, high-arched palate) and congenital anomalies/malformations of the eye (blue sclera), cardiopulmonary (atrial septal defect, prominent thoracic and abdominal veins), and skeletal (clinodactyly, syndactyly of the fingers and 2nd and 3rd toes) systems. There have been no further descriptions in the literature since 1980.

739
(66.1%)

Frontonasal dysplasia-bifid nose-upper limb anomalies syndrome

Abnormality of the hand Almond-shaped palpebral fissure Clinodactyly of the 5th finger Frontal encephalocele Thin upper lip vermilion

739
(66.1%)

Cerebrooculonasal syndrome

Brachycephaly Epicanthus Long philtrum Postaxial hand polydactyly

Autosomal dominant inheritance

Cerebro-oculo-nasal syndrome is a multisystem malformation syndrome that has been reported in about 10 patients. The clinical features include bilateral anophthalmia, abnormal nares, central nervous system anomalies, and neurodevelopmental delay.

739
(66.1%)

Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

Brachycephaly Epicanthus Tapered finger Thin upper lip vermilion

Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome is a rare, syndromic intellectual disability primarily characterized by moderate to severe intellectual disability, true-to-relative microcephaly and brain abnormalities including a thin corpus callosum, cerebellar hypoplasia, cerebral white matter hypoplasia and multi-focal hyperintensity of cerebral white matter on MRI. Obesity and distinctive craniofacial dysmorphism (including brachycephaly, round face, straight eyebrows, synophrys, hypertelorism, epicanthus, wide and depressed nasal bridge, protruding ears with uplifted lobe, downslanting corners of the mouth) are additional features.

739
(66.1%)

Proximal 16p11.2 microduplication syndrome

Arachnodactyly Microcephaly Sparse eyelashes Thin upper lip vermilion

Proximal 16p11.2 microduplication syndrome is a rare chromosomal anomaly syndrome resulting from a partial duplication of the short arm of chromosome 16 characterized by developmental delay and intellectual disability of a highly variable degree, autism spectrum, obsessive-compulsive, attention deficit hyperactivity disorder, speech articulation abnormalities, muscular hypotonia, tremor, hyper- or hyporeflexia, seizures, microcephaly, neuroimaging abnormalities, decreased body mass index and schizophrenia or bipolar disorder later on in life.

739
(66.1%)

3q29 microdeletion syndrome

Downslanted palpebral fissures Microcephaly Short philtrum Tapered finger

Autosomal dominant inheritance Sporadic

A recurrent subtelomeric deletion syndrome with variable clinical manifestations including intellectual deficit and dysmorphic features.

739
(66.1%)

KBG syndrome

Finger clinodactyly Microcephaly Single transverse palmar crease Telecanthus Thin upper lip vermilion

Autosomal dominant inheritance

KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and developmental delay.

747
(66.1%)

GM1 gangliosidosis

Abnormal diaphysis morphology Camptodactyly of finger Long philtrum Macroglossia Mandibular prognathia

GM1 gangliosidosis is a rare lysosomal storage disorder characterized biochemically by deficient beta-galactosidase activity and clinically by a wide range of variable neurovisceral, ophthalmological and dysmorphic features.

748
(66.1%)

Distal trisomy 18q

High palate Large hands Micrognathia

Distal trisomy 18q is a rare, partial autosomal trisomy characterized by a variable phenotype that includes hypotonia, motor delay, mild to severe intellectual disability, seizures, variable cerebral anomalies, finger/toe syndactyly, fifth finger clinodactyly, strabismus, short neck and dysmorphic facial features.

749
(66.0%)

Spondylometaphyseal dysplasia, A4 type

Micromelia Platyspondyly Short palm

Autosomal recessive inheritance

Spondylometaphyseal dysplasia, A4 type is a rare primary bone dysplasia disorder characterized by disproportionate short stature, severe femoral neck deformity, marked metaphyseal abnormalities and platyspondyly consisting of ovoid vertebral bodies that have an anterior tongue-like deformity.

749
(66.0%)

Multiple epiphyseal dysplasia type 1

Gait disturbance Micromelia Short palm

Autosomal dominant inheritance Heterogeneous

Multiple epiphyseal dysplasia type 1 (MED 1) is a form of multiple epiphyseal dysplasia that is characterized by normal or mild short stature, pain in the hips and/or knees, progressive deformity of extremities and early-onset osteoarthrosis. Specific features to MED 1 include a more pronounced involvement of hip joints and gait abnormality and a shorter adult height. MED1 is allelic to pseudoachondroplasia with which it shares clinical and radiological features. The disease follows an autosomal dominant mode of transmission.

749
(66.0%)

Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome

Astigmatism Rhizomelia Short palm

Autosomal recessive inheritance

Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome is characterised by the association of spondylometaphyseal dysplasia (marked by platyspondyly, shortening of the tubular bones and progressive metaphyseal irregularity and cupping), with postnatal growth retardation and progressive visual impairment due to cone-rod dystrophy. So far, it has been described in eight individuals. Transmission appears to be autosomal recessive.

752
(66.0%)

Ring chromosome 4 syndrome

Abnormality of the ulna Aplasia/Hypoplasia of the radius Microcephaly Micrognathia

Ring chromosome 4 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including significant intrauterine and postnatal growth retardation, developmental delay, intellectual disability, microcephaly, and dysmorphic facial features. Some less frequent features are cleft lip and/or cleft palate, congenital cardiovascular, gastrointestinal and genitourinary system anomalies.

753
(66.0%)

Noonan syndrome-like disorder with loose anagen hair

Abnormality of the elbow Brachydactyly Deep philtrum Epicanthus Pectus excavatum

Noonan-like syndrome with loose anagen hair (NS/LAH) is a Noonan-related syndrome, characterized by facial anomalies suggestive of Noonan syndrome (see this term); a distinctive hair anomaly described as loose anagen hair syndrome (see this term); frequent congenital heart defects; distinctive skin features with darkly pigmented skin, keratosis pilaris, eczema or occasional neonatal ichtyosis (see this term); and short stature, often associated with a GH deficiency and psychomotor delays.

754
(65.9%)

9p13 microdeletion syndrome

Clinodactyly of the 5th finger Epicanthus High palate Microretrognathia

9p13 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from a partial interstitial deletion of the short arm of chromosome 9, characterized by mild to moderate developmental delay, hand tremors, myoclonic jerks, attention deficit-hyperactivity disorder and a social personality. Patients also present bruxism, short stature and minor facial dysmorphic features (e.g., bilateral epicantic folds, broad, flat nasal bridge, anteverted nares, low-set ears micro/retro-gnathia).

754
(65.9%)

CK syndrome

Epicanthus High palate Long fingers Microretrognathia

X-linked recessive inheritance

CK syndrome is a rare, genetic, X-linked syndromic intellectual disability disorder characterized by mild to severe intellectual disability, infancy-onset seizures, post-natal microcephaly, cerebral cortical malformations, dysmorphic facial features (including long, narrow face, almond-shaped palpebral fissures, epicanthic folds, high nasal bridge, malar flattening, posteriorly rotated ears, high arched palate, crowded teeth, micrognathia) and thin body habitus. Long and slim fingers/toes, strabismus, hypotonia, spasticity, optic disc atrophy, and behavioral problems (aggression, attention deficit hyperactivity disorder and irritability) are additional features.

754
(65.9%)

Czeizel-Losonci syndrome

High palate Micrognathia Radial deviation of the thumb Upslanted palpebral fissure

Autosomal dominant inheritance

Czeizel-Losonci syndrome (CLS) is an exceedingly rare, severe, congenital genetic malformation disorder characterized by split hand/split foot, hydronephrosis, and spina bifida. Spinal and skeletal manifestations were thoracolumbar scoliosis, spinabifida (spina bifida occulta or spina bifida cystic), Bochdalek diaphragmatic hernia, and radial defects.There have been no further descriptions in the literature since 1987.

754
(65.9%)

Neonatal Marfan syndrome

Arachnodactyly Downslanted palpebral fissures High, narrow palate Microretrognathia

Neonatal Marfan syndrome is a rare, severe and life-threatening genetic disease, occuring during the neonatal period, characterized by classical Marfan syndrome manifestations in addition to facial dysmorphism (megalocornea, iridodonesis, ectopia lentis, crumpled ears, loose redundant skin giving a 'senile' facial appearance), flexion joint contractures, pulmonary emphysema, and a severe, rapidly progressive cardiovascular disease (including ascending aortic dilatation and severe mitral and/or tricuspid valve insufficiency). Additionally, skeletal manifestations (arachnodactyly, dolichostenomelia, pectus deformities) are also associated.

758
(65.8%)

Night blindness-skeletal anomalies-dysmorphism syndrome

Abnormal palate morphology Brachydactyly Clinodactyly of the 5th finger Epicanthus Retrognathia

This syndrome is characterized by night blindness, skeletal abnormalities (sloping shoulders, joint hyperextensibility, minor radiological anomalies) and characteristic facies (periorbital anomalies, malar flatness, retrognathia).

759
(65.7%)

Lamellar ichthyosis

Brachydactyly Everted lower lip vermilion Genu valgum Kyphoscoliosis Telecanthus

Lamellar ichthyosis (LI) is a keratinization disorder characterized by the presence of large scales all over the body without significant erythroderma.

760
(65.7%)

Odontochondrodysplasia

Delayed eruption of teeth Micromelia Retrognathia Short palm

Autosomal dominant inheritance

Odontochondrodysplasia, also called Goldblatt syndrome, is a very rare syndrome associating chondrodysplasia with dentinogenesis imperfecta.

761
(65.7%)

Congenital dyserythropoietic anemia type III

Gingival bleeding Short metatarsal

Autosomal dominant inheritance Autosomal recessive inheritance

Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA (see this term) characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia.

762
(65.7%)

Grange syndrome

Hypertension Short palm

Autosomal dominant inheritance Autosomal recessive inheritance

Grange syndrome is characterised by stenosis or occlusion of multiple arteries (including the renal, cerebral and abdominal vessels), hypertension, brachysyndactyly, syndactyly, increased bone fragility, and learning difficulties or borderline intellectual deficit. Congenital heart defects were also reported in some cases.

762
(65.7%)

Geleophysic dysplasia

Acromelia Glaucoma Small hand

A rare skeletal dysplasia characterized by short stature, prominent abnormalities in hands and feet, and a characteristic facial appearance (described as happy'').

762
(65.7%)

Syndactyly type 2

Short foot Short palm Syndactyly

Syndactyly type 2 or synpolydactyly (SPD) is a rare congenital distal limb malformation characterized by the combination of syndactyly and polydactyly.

762
(65.7%)

Colonic atresia

Absent hand Hydrocephalus

X-linked inheritance

Colonic atresia is a congenital intestinal malformation resulting in a non-latent segment of the colon and characterized by lower intestinal obstruction manifesting with abdominal distention and failure to pass meconium in newborns.

762
(65.7%)

Achromatopsia

Retinopathy Small hand

A rare autosomal recessive retinal disorder characterized by color blindness, nystagmus, photophobia, and severely reduced visual acuity due to the absence or impairment of cone function.

767
(65.6%)

Dysmorphism-pectus carinatum-joint laxity syndrome

Deep philtrum Genu valgum Malar flattening Telecanthus

Dysmorphism-pectus carinatum-joint laxity syndrome is characterised by joint laxity, pectus carinatum and facial dysmorphism (mild frontal bossing, a beaked nose with a low nasal bridge, malar hypoplasia, chubby cheeks, a striking philtrum and arched upper lips). It has been described in two siblings. The mode of transmission is unknown.

768
(65.6%)

Gastroschisis

Brachydactyly Meromelia Shallow orbits

Gastroschisis is marked by viscera protruding, without a covering sac, from the fetal abdomen on the right lateral base of the umbilicus. It is due to defective embryo growth and other malformations are only exceptionally associated.

769
(65.6%)

Vaginal atresia

Bifid nasal tip Cryptophthalmos Y-shaped metacarpals

770
(65.6%)

Opsismodysplasia

Brachydactyly Broad thumb Frontal bossing Hypoplastic vertebral bodies

Autosomal recessive inheritance

Opsismodysplasia is a skeletal dysplasia characterized by congenital dwarfism and facial dysmorphism.

771
(65.6%)

Left ventricular noncompaction

Absent thumb Pierre-Robin sequence

Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized anatomically by prominent left ventricular trabeculae and deep intratrabecular recesses causing progressive systolic and diastolic dysfunction, conduction abnormalities, and occasionally thromboembolic events.

772
(65.5%)

Craniosynostosis-fibular aplasia syndrome

Abnormal palate morphology Cleft palate Fibular aplasia

Autosomal recessive inheritance

Craniosynostosis-fibular aplasia syndrome is an extremely rare genetic disease, reported in only 2 brothers to date, characterized by the combination of craniosynostosis (involving both coronal sutures), congenital absence of the fibula, cryptorchidism, and bilateral simian creases. Intelligence is normal and an autosomal recessive mode of inheritance has been proposed. There have been no further reports in the literature since 1972.

773
(65.5%)

Tetrasomy X

Abnormality of the dentition Brachydactyly Epicanthus Radioulnar synostosis

Tetrasomy X is a sex chromosome anomaly caused by the presence of two extra X chromosomes in females (48,XXXX instead of 46,XX).

774
(65.5%)

Amyotrophic lateral sclerosis

Small hand Tongue fasciculations Trismus Xerostomia

A neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.

775
(65.5%)

Sturge-Weber syndrome

Conjunctival telangiectasia Gingival overgrowth Hemiatrophy

Autosomal dominant inheritance Sporadic

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial capillary malformations and/or cerebral and ocular ipsilateral vascular malformations that result in variable degrees of ocular and neurological anomalies.

775
(65.5%)

Systemic sclerosis

Hemiatrophy Keratoconjunctivitis sicca Narrow mouth

Systemic sclerosis (SSc) is a generalized disorder of small arteries, microvessels and connective tissue, characterized by fibrosis and vascular obliteration in the skin and organs, particularly the lungs, heart, and digestive tract. There are two main subsets of SSc: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) (see these terms). A third subset of SSc has also been observed, called limited Systemic Sclerosis (lSSc) or systemic sclerosis sine scleroderma (see these terms).

777
(65.5%)

Cocaine embryofetopathy

Encephalocele Short distal phalanx of finger

Cocaine embryofetopathy is a group of clinical signs observed in newborns exposed in utero to cocaine, a short-acting central nervous system stimulant used as a recreational drug through inhalation of the powder or intravenous injection. Cocaine use during pregnancy is associated with intrauterine growth restriction, low birth weight, seizures, respiratory distress (decreased apnea density and periodic breathing), feeding difficulties, irritability and lability of state, decreased behavioral and autonomic regulation, poor alertness and orientation and cognitive impairment (impaired auditory information processing , visual-spatial delay and subtle language delay) in the offspring.

777
(65.5%)

Aphalangy-syndactyly-microcephaly syndrome

Microcephaly Short distal phalanx of finger

Autosomal dominant inheritance Autosomal recessive inheritance

An extremely rare malformation syndrome characterized by the association of partial distal aphalangia with syndactyly, duplication of metatarsal IV, microcephaly, and mild intellectual disability.

777
(65.5%)

Adams-Oliver syndrome

Absent hand Microcephaly Short distal phalanx of finger

A rare disorder characterized by the combination of congenital limb abnormalities and scalp defects, often accompanied by skull ossification defects.

780
(65.4%)

Alacrimia-choreoathetosis-liver dysfunction syndrome

Acromesomelia Facial hypotonia Lagopthalmos Sclerosis of finger phalanx

Autosomal recessive inheritance

A rare, genetic, inborn error of metabolism disorder characterized by global developmental delay, hypotonia, choreoathetosis, hypo-/alacrimia, and liver dysfunction which manifests with elevated liver transanimases and hepatocyte cytoplasmic storage material or vacuolization on liver biposy. Additional features reported include acquired microcephaly, hypo-/areflexia, seizures, peripheral neuropathy, intellectual and language/speech disability, additional ocular anomalies and EEG and brain imaging abnomalities.

781
(65.4%)

Syndromic X-linked intellectual disability due to JARID1C mutation

High palate Hypoplasia of the maxilla Short palm

X-linked recessive inheritance

Syndromic X-linked intellectual disability due to JARID1C mutation is characterised by mild to severe intellectual deficit associated with variable clinical manifestations including spasticity, cryptorchidism, maxillary hypoplasia, alopecia areata, epilepsy, short stature, impaired speech and behavioural problems. To date, it has been described in less than 15 families. Transmission is X-linked recessive and the syndrome is caused by mutations in the JARID1C (SMCX) gene encoding a JmjC-domain protein with histone demethylase activity.

782
(65.4%)

Axial spondylometaphyseal dysplasia

Anteverted nares Downslanted palpebral fissures Rhizomelia

Autosomal recessive inheritance

Axial spondylometaphyseal dysplasia is a rare type of spondylometaphyseal dysplasia characterized by metaphyseal changes of the truncal-juxtatruncal bones associated with retinal dystrophy. Patients typically present progressive postnatal growth failure with rhizomelic shortening of the limbs, a deformed, hypoplastic thorax and retinitis pigmentosa or pigmentary retinal degeneration. Radiographic findings include short ribs with flared, cupped anterior ends, mild platyspondyly, lacy ilia and metaphyseal dysplasia of the proximal femora.

782
(65.4%)

Juvenile glaucoma

Ectropion Hemiatrophy

A rare autosomal dominant open angle glaucoma, characterized by early onset, severe elevation of intra ocular pressure of rapid progression, leading to optic nerve excavation and, when untreated, substantial visual impairment.

782
(65.4%)

Hypertrichosis cubiti

Abnormal eyelid morphology Abnormality of the face Micromelia

Hypertrichosis cubiti is a rare hair anomaly characterized by symmetrical, congenital or early-onset, bilateral hypertrychosis localized on the externsor surfaces of the upper extremities (especially the elbows). Short stature, or other abnormalities, such as developmental delay, facial anomalies and intellectual disability, may or may not be associated.

782
(65.4%)

Linear nevus sebaceus syndrome

Facial asymmetry Hemiatrophy Telecanthus

Somatic mosaicism

Linear nevus sebaceous syndrome (LNSS) is characterized by the association of a large sebaceous nevus, usually appearing on the face or on the scalp, with a broad spectrum of abnormalities that may affect every organ system, including the central nervous system (brain neoplasms, hemimegalencephaly and lateral ventricle enlargement).

782
(65.4%)

Neurofibromatosis type 1

Abnormal eyelid morphology Facial asymmetry Hemiatrophy

Autosomal dominant inheritance

Neurofibromatosis type 1 (NF1) is a clinically heterogeneous, neurocutaneous genetic disorder characterized by café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, and multiple neurofibromas.

787
(65.4%)

Tetraamelia-multiple malformations syndrome

Micrognathia Narrow mouth Oral cleft Tetraamelia

Tetraamelia - multiple malformations is an extremely rare mostly lethal congenital disorder characterized by absence of all four limbs and frequent associated major malformations involving the head, face, eyes, skeleton, heart, lungs, anus, urogenital, and central nervous systems. The syndrome has been described in fewer than 20 patients mainly of middle Eastern descent.

788
(65.4%)

Spondyloepiphyseal dysplasia congenita

Cleft palate Micromelia

Autosomal dominant inheritance

Spondyloepiphyseal dysplasia congenita (SEDC) is a chondrodysplasia characterized by disproportionate short stature, abnormal epiphyses and flattened vertebral bodies.

788
(65.4%)

Septo-optic dysplasia spectrum

Cleft palate Hemiatrophy

Autosomal dominant inheritance Autosomal recessive inheritance

Septooptic dysplasia (SOD) is a clinically heterogeneous disorder characterized by the classical triad of optic nerve hypoplasia, pituitary hormone abnormalities and midline brain defects.

790
(65.4%)

3q13 microdeletion syndrome

Abnormality of the fontanelles or cranial sutures Abnormality of the hand Epicanthus Long philtrum

Autosomal dominant inheritance

3q13 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 3. Phenotype can be highly variable, but it is primarily characterized by significant developmental delay, postnatal growth above the mean, muscular hypotonia and distinctive facial features (such as broad and prominent forehead, hypertelorism, epicantic folds, anti-mongloid slanted eyes, ptosis, short philtrum, protruding lips with a full lower lip, high arched palate). Abnormal hypoplastic male genitalia and skeletal abnormalities are frequently present.

790
(65.4%)

Monosomy 9q22.3

Epicanthus Long philtrum Palmar pits Trigonocephaly

Interstitial 9q22.3 microdeletion is associated with a phenotype including macrocephaly, overgrowth and trigonocephaly. Psychomotor delay, hyperactivity and distinctive facial features were also observed. It has been described in two unrelated children.

792
(65.4%)

Spondylometaphyseal dysplasia, Schmidt type

Micromelia Myopia Short long bone

Autosomal dominant inheritance

Spondylometaphyseal dysplasia, Schmidt type is characterized by short stature, myopia, ,small pelvis, progressive kypho-scoliosis, wrist deformity, severe genu valgum, short long bones, and severe metaphyseal dysplasia with moderate spinal changes and minimal changes in the hands and feet.

793
(65.3%)

X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome

Mandibular prognathia Single transverse palmar crease Tapered finger Thin upper lip vermilion

X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome is a rare syndromic intellectual disability characterized by hypotonia, microcephaly, severe developmental delay, seizures, intellectual disability, growth retardation, cardiovascular septal defects, cryptorchidism, hypospadias, and dysmorphic features - prominent ears, prognathism, thin upper lip, dental crowding.

793
(65.3%)

Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome

Mandibular prognathia Short philtrum Tapered finger

793
(65.3%)

TMEM70-related mitochondrial encephalo-cardio-myopathy

Camptodactyly of finger Retrognathia Short philtrum Wide mouth

Autosomal recessive inheritance

Mitochondrial encephalo-cardio-myopathy due to TMEM70 mutation is characterized by early neonatal onset of hypotonia, hypetrophic cardiomyopathy and apneic spells within hours after birth accompanied by lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria.

796
(65.3%)

Hyperphalangy

Brachydactyly Micrognathia Pierre-Robin sequence Pulp stones Short hallux

Hyperphalangy is a congenital, non-syndromic limb malformation characterized by the presence of an accessory phalanx between metacarpal/metatarsal and proximal phalanx, or between any two other phalanges of a digit, excluding the thumb. Hypherphalangy is almost always bilateral and patients present no more than five digits and no other skeletal anomalies.

796
(65.3%)

Laron syndrome

Brachydactyly Delayed eruption of teeth High forehead Micrognathia Short toe

Autosomal recessive inheritance

Laron syndrome is a congenital disorder characterized by marked short stature associated with normal or high serum growth hormone (GH) and low serum insulin-like growth factor-1 (IGF-I) levels which fail to rise after exogenous GH administration.

798
(65.3%)

Xq12-q13.3 duplication syndrome

2-3 toe syndactyly Epicanthus Everted lower lip vermilion Microcephaly

Xq12-q13.3 duplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome X, characterized by global developmental delay, autistic behavior, microcephaly and facial dysmorphism (including down-slanting palpebral fissures, depressed nasal bridge, anteverted nares, long philtrum, down-slanting corners of the mouth). Seizures have also been reported in some patients.

799
(65.2%)

Lethal hemolytic anemia-genital anomalies syndrome

Micrognathia Narrow mouth Thin vermilion border

A rare syndrome characterized by the association of lethal non-spherocytic, non-immune hemolytic anemia with abnormalities of the external genitalia (micropenis and hypospadias), flat occiput, dimpled earlobes, deep plantar creases, and increased space between the first and second toes. It has been described only once in two brothers who died a few hours after birth. The second-born infant had massive ascites and hepatosplenomegaly. The mother had two spontaneous abortions (at 6 and 12 weeks gestation) but gave birth to a normal girl, suggesting an autosomal or X-linked recessive mode of inheritance. Although the parents were not known to be consanguineous, they shared a French-Canadian and American Indian ethnic origin.

799
(65.2%)

Congenital unilateral hypoplasia of depressor anguli oris

Abnormality of lower lip Cleft palate Micrognathia

Autosomal dominant inheritance

Congenital unilateral hypoplasia of depressor anguli oris is a congenital anomaly, characterized by the unilateral hypoplasia/agenesis of the depressor anguli oris muscle, resulting in an asymmetric crying facies in neonatal period/ infancy (drooping of one corner of the mouth during crying) while eye closure, nasolabial fold and forehead wrinkling are symmetric. While it can be isolated, this anomaly is also seen in 22q11.2 deletion syndrome (see this term) and can be accompanied by other major congenital anomalies of the cardiovascular system, as well as less frequently the musculoskeletal, cervicofacial, respiratory, genitourinary, and, rarely, endocrine systems. When isolated, the condition is cosmetically insignificant as the infant gets older (as the muscle does not contribute significantly to facial expression in childhood/ adulthood).