301
(73.1%)

Dysraphism-cleft lip/palate-limb reduction defects syndrome

Aplasia/Hypoplasia of the radius Cleft palate Non-midline cleft lip

301
(73.1%)

Holoprosencephaly-caudal dysgenesis syndrome

Median cleft lip Radial club hand

Holoprosencephaly-caudal dysgenesis syndrome is a central nervous system malformation syndrome characterized by holoprosencephaly with microcephaly, abnormal eye morphology (hypotelorism, cyclopia, exophthalmos), nasal anomalies (single nostril or absent nose), and cleft lip/palate, combined with signs of caudal regression (sacral agenesis, sirenomelia with absent external genitalia).

301
(73.1%)

Pentalogy of Cantrell

Aplasia/Hypoplasia of the radius Cleft palate Non-midline cleft lip

X-linked inheritance

Pentalogy of Cantrell (POC) is a lethal multiple congenital anomalies syndrome, characterized by the presence of 5 major malformations: midline supraumbilical abdominal wall defect, lower sternal defect, diaphragmatic pericardial defect, anterior diaphragmatic defect and various intracardiac malformations. Ectopia cordis (EC) is often found in fetuses with POC.

301
(73.1%)

VACTERL/VATER association

Aplasia/Hypoplasia of the radius Cleft palate Non-midline cleft lip

Sporadic

VACTERL/VATER is an association of congenital malformations typically characterized by the presence of at least three of the following: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities.

305
(73.1%)

Platyspondylic dysplasia, Torrance type

Cleft palate Hypoplastic scapulae Micromelia Short distal phalanx of finger

Autosomal dominant inheritance

Platyspondylic lethal skeletal dysplasia (PLSD), Torrance type (PLSD-T) is a skeletal dysplasia characterised by severe limb shortening (short and broad long bones), platyspondyly with wafer-like vertebral bodies, short ribs with anterior cupping, severe hypoplasia of the lower ilia and radial bowing. Histological findings include slightly enlarged chondrocytes and hypercellularity. The prevalence is unknown. The disorder is transmitted as an autosomal dominant trait and is caused by mutations in the C-propeptide domain of the COL2A1 gene. Although PLSD-T is generally lethal, survival to adulthood has been reported in two families.

306
(73.1%)

Thanatophoric dysplasia

Bifid tongue Brachydactyly Downslanted palpebral fissures Micrognathia Short femur

Thanatophoric dysplasia (TD) is a severe and generally lethal skeletal dysplasia presenting in the prenatal period and characterized by micromelia, macrocephaly, narrow thorax, and distinctive facial features. It includes TD, type 1 (TD1) and TD, type 2 (TD2) (see these terms), that can be differentiated from each other by femur and skull shape.

307
(73.0%)

Thumb deformity-alopecia-pigmentation anomaly syndrome

Everted lower lip vermilion Short thumb

Autosomal dominant inheritance

Thumb deformity-alopecia-pigmentation anomaly syndrome is a rare, genetic, congenital limb malformation syndrome characterized by short stature, sparse scalp hair, hypoplastic, proximally-placed thumbs, and skin hyperpigmentation with areas of 'raindrop' depigmentation. Presence of a single, upper central incisor has also been reported. There have been no further descriptions in the literature since 1988.

308
(73.0%)

X-linked dominant chondrodysplasia, Chassaing-Lacombe type

Micrognathia Rhizomelia Short palm Short philtrum Wide mouth

X-linked dominant inheritance

X-linked dominant chondrodysplasia Chassaing-Lacombe type is a rare genetic bone disorder characterized by chondrodysplasia, intrauterine growth retardation (IUGR), hydrocephaly and facial dysmorphism in the affected males.

309
(72.9%)

Marfanoid habitus-autosomal recessive intellectual disability syndrome

Abnormality of the palpebral fissures Arachnodactyly Broad philtrum Malar flattening Thin metacarpal cortices

Autosomal recessive inheritance

Marfanoid habitus – intellectual deficit, autosomal recessive is a very rare multiple congenital anomalies syndrome described in four sibs and characterized by intellectual deficit, flat face and some skeletelal features of Marfan syndrome (see this term) such as tall stature, dolichostenomelia, arm span larger than height, arachnodactyly of hands and feet, little subcutaneous fat, muscle hypotonia and intellectual deficit.

310
(72.9%)

48,XXXY syndrome

Cleft palate Clinodactyly of the 5th finger Epicanthus Mandibular prognathia Radioulnar synostosis

The 48,XXXY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of two extra X chromosomes in males.

310
(72.9%)

49,XXXXY syndrome

Cleft palate Clinodactyly of the 5th finger Epicanthus Mandibular prognathia Radioulnar synostosis

The 49,XXXXY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of three extra X chromosomes in males.

312
(72.9%)

Microcephaly-corpus callosum and cerebellar vermis hypoplasia-facial dysmorphism-intellectual disability syndrom

Abnormal size of the palpebral fissures Acromesomelia Open mouth Short 5th finger

312
(72.9%)

West syndrome

Hemiatrophy Hordeolum Short thumb Wide mouth

A rare disorder characterized by the association of clusters of axial spasms, psychomotor retardation and an hypsarrhythmic interictal EEG pattern. It is the most frequent type of epileptic encephalopathy. It may occur in otherwise healthy infants and in those with abnormal cognitive development.

314
(72.9%)

Oliver syndrome

Mandibular prognathia Short philtrum Short toe Thick eyebrow

Autosomal recessive inheritance

Oliver syndrome is a very rare syndrome characterized by intellectual deficit, postaxial polydactyly, and epilepsy.

315
(72.9%)

14q22q23 microdeletion syndrome

Downturned corners of mouth Epicanthus Micrognathia Short 4th metacarpal Short palm

Autosomal dominant inheritance

14q22q23 microdeletion syndrome is a rare partial deletion of the long arm of chromosome 14 characterized by ocular anomalies (anopthalmia/microphthalmia, ptosis, hypertelorism, exophthalmos), pituitary anomalies (pituitary hypoplasia/aplasia with growth hormone deficiency and growth retardation) and hand/foot anomalies (polydactyly, short digits, pes cavus). Other clinical features may include muscular hypotonia, psychomotor development delay/intellectual disability, dysmorphic signs (facial asymmetry, microretrognathia, high-arched palate, ear anomalies), congenital genitourinary malformations, hearing impairment. Smaller 14q22 deletions may have variable expression.

316
(72.9%)

Esophageal atresia

Absent radius Cleft lip Glossoptosis Micrognathia

Oesophageal atresia (OA) encompasses a group of congenital anomalies with an interruption in the continuity of the oesophagus, with or without persistent communication with the trachea.

316
(72.9%)

Dextrocardia

Cleft lip Micrognathia Preauricular skin tag Radial club hand

A rare, congenital, non-syndromic, developmental defect during embryogenesis characterized by positioning of the heart in the right hemithorax, with the base and apex of the heart pointing caudally and to the right, due to abnormalities of embryologic origin that are intrinsic to the heart itself. Situs inversus or situs solitus may be associated, with extracardiac visceral transposition anomalies usually present in the former case and additional cardiac defects (e.g. septal defects, transposition of the great arteries, double-outlet right ventricles, anomalous pulmonary venous return, tetralogy of Fallot) frequently observed in both cases.

318
(72.9%)

Holoprosencephaly-craniosynostosis syndrome

Epicanthus Hypoplastic vertebral bodies Short distal phalanx of finger

Holoprosencephaly-craniosynostosis syndrome is a rare developmental defect during embryogenesis syndrome characterized by the association of primary craniosynostosis (usually involving the coronal and metopic sutures) with holoprosencephaly (ranging from alobar to, most commonly, semilobar) and various skeletal anomalies (typically, hand and feet anomalies including fifth digit clinodactyly, hypoplastic phalanges and cone-shaped epiphyses, small vertebral bodies, scoliosis, coxa valga and/or flexion deformities of hips). Craniofacial asymmetry, microcephaly, brachy/plagiocephaly, short stature and psychomotor delay are additional common features.

319
(72.9%)

8q12 microduplication syndrome

Epicanthus Long philtrum Short foot

The newly described 8q12 microduplication syndrome is associated with unusual and characteristic multi-organ clinical features, which include hearing loss, congenital heart defects, intellectual disability, hypotonia in infancy, and Duane anomaly (see this term).

320
(72.9%)

Tuberculosis

Cheilitis Epicanthus Finger swelling Short tubular bones of the hand Sinusitis

Tuberculosis (TB) is a contagious-infectious disease caused mainly by Mycobacterium tuberculosis that in most individuals is usually asymptomatic but that in at risk individuals (e.g. with diabetes or with HIV infection) can cause weakness, fever, weight loss, night sweat, and respiratory anomalies such as chronic cough, chest pain, hemoptysis or respiratory insufficiency.

321
(72.9%)

Autosomal recessive amelia

Amelia involving the upper limbs Micrognathia Non-midline cleft lip Oral cleft

Autosomal recessive inheritance

A rare disorder characterised by the absence of the upper limbs and severe underdevelopment of the lower limbs. Minor facial abnormalities (depressed nasal root, upturned nose, infra-orbital creases, prominent cheeks and micrognathia) were also reported. The syndrome has been described in three foetuses born to non consanguineous parents.

322
(72.9%)

Stickler syndrome

Abnormal diaphysis morphology Arachnodactyly Cleft upper lip Epicanthus Micrognathia

Stickler syndrome is an inherited vitreoretinopathy characterized by the association of ocular signs with more or less complete forms of Pierre-Robin sequence (see this term), bone disorders, and sensorineural deafness (10% of cases).

323
(72.8%)

SHOX-related short stature

Forearm undergrowth High palate Micrognathia

X-linked inheritance

SHOX-related short stature is a primary bone dysplasia characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones. Patients present normal bone age with normal limbs, shortening of the extremities (significantly lower extremities-trunk and sitting height-to-height ratios), normal hGH values, normal karyotype, and Leri-Weill dyschondrosteosis-like radiological signs (e.g. triangularization of distal radial epiphyses, pyramidalization of distal carpal row, and lucency of the distal radius on the ulnar side). Mesomelic disproportions and Madelung deformity are not apparent at a young age, but may develop later in life or never.

324
(72.8%)

Neurofaciodigitorenal syndrome

Abnormality of the metacarpal bones Abnormality of the philtrum Epicanthus Mandibular prognathia Triphalangeal thumb

Autosomal recessive inheritance

Neurofaciodigitorenal syndrome is a rare multiple developmental anomalies syndrome characterized by neurological abnormalities (including megalencephaly, hypotonia, intellectual disability, abnormal EEG), dysmorphic facial features (high prominent forehead, grooved nasal tip, ptosis, ear anomalies) and acrorenal defects (such as triphalangism, broad halluces, unilateral renal agenesis). Additionally, intrauterine growth restriction, short stature and congenital heart defects may be associated. There have been no further descriptions in the literature since 1997.

325
(72.8%)

ADNP syndrome

Blepharophimosis Brachydactyly Broad thumb Thin upper lip vermilion Trigonocephaly

Autosomal dominant inheritance

A rare syndromic intellectual disability characterized by global developmental delay, gastrointestinal problems, hypotonia, delayed speech, behavioral and sleep problems, pain insensitivity, seizures, structural brain anomalies, dysmorphic features, visual problems, early tooth eruption and autistic features.

325
(72.8%)

Retinitis pigmentosa

Bowed humerus Brachydactyly Long eyelashes Microcephaly Short philtrum

Autosomal dominant inheritance Autosomal recessive inheritance X-linked recessive inheritance Mitochondrial inheritance

Retinitis pigmentosa (RP) is an inherited retinal dystrophy leading to progressive loss of the photoreceptors and retinal pigment epithelium and resulting in blindness usually after several decades.

327
(72.8%)

Sanjad-Sakati syndrome

Abnormality of the dentition Long philtrum Micrognathia Small hand

Autosomal recessive inheritance

Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism - intellectual disability-dysmorphism, is a rare multiple congenital anomaly syndrome, mainly occurring in the Middle East and the Arabian Gulf countries, characterized by intrauterine growth restriction at birth, microcephaly, congenital hypoparathyroidism (that can cause hypocalcemic tetany or seizures in infancy), severe growth retardation, typical facial features (long narrow face, deep-set eyes, beaked nose, floppy and large ears, long philtrum, thin lips and micrognathia), and mild to moderate intellectual deficiency. Ocular findings (i.e. nanophthalmos, retinal vascular tortuosity and corneal opacification/clouding) and superior mesenteric artery syndrome have also been reported. Although SSS shares the same locus with the autosomal recessive form of Kenny-Caffey syndrome (see this term), the latter differs from SSS by its normal intelligence and skeletal features.

328
(72.7%)

Facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome

Abnormality of the dentition Epicanthus Short distal phalanx of finger

Autosomal recessive inheritance

A rare disorder characterized by Dandy-Walker malformation, severe intellectual deficit, macrocephaly, brachytelephalangy, facial dysmorphism and severe myopia. Three cases have been described. Transmission appears to be autosomal recessive.

328
(72.7%)

Alopecia-contractures-dwarfism-intellectual disability syndrome

Abnormality of dental enamel Short middle phalanx of finger Upslanted palpebral fissure

Autosomal recessive inheritance

A form of ectodermal dysplasia syndrome characterized by a short stature of prenatal onset, alopecia, ichthyosis, photophobia, ectrodactyly, seizures, scoliosis, multiple contractures, fusions of various bones (particularly elbows, carpals, metacarpals, and spine), intellectual disability, and facial dysmorphism (microdolichocephaly, madarosis, large ears and long nose). ACD syndrome overlaps with ichthyosis follicularis-alopecia-photophobia syndrome.

330
(72.7%)

Upper limb defect-eye and ear abnormalities syndrome

Epicanthus Short metacarpal Short thumb

Autosomal recessive inheritance

Upper limb defect - eye and ear abnormalities syndrome associates upper limb defects (hypoplastic thumb with hypoplasia of the metacarpal bone and phalanges and delayed bone maturation), developmental delay, central hearing loss, unilateral poorly developed antihelix, bilateral choroid coloboma and growth retardation.

330
(72.7%)

Sillence syndrome

Broad thumb Epicanthus Short middle phalanx of finger

Autosomal dominant inheritance

Sillence syndrome (brachydactyly-symphalangism syndrome) resembles type A1 brachydactyly (variable shortening of the middle phalanges of all digits) with associated symphalangism (producing a distal phalanx with the shape of a chess pawn). Scoliosis, clubfoot and tall stature are also characteristic.

332
(72.7%)

Acropectorovertebral dysplasia

Broad thumb Cleft palate Short distal phalanx of finger

Autosomal dominant inheritance

A rare skeletal dysplasia characterized by fusion of the carpal and tarsal bones, with complex anomalies of the fingers and toes (preaxial polydactyly of the hands and/or feet, syndactyly of fingers and toes, hypoplasia and dysgenesis of metatarsal bones).

332
(72.7%)

Larsen syndrome

Broad distal phalanx of finger Cleft palate Short distal phalanx of finger

Autosomal dominant inheritance

Larsen syndrome (LS) is a rare skeletal dysplasia characterized by congenital dislocation of large joints, foot deformities, cervical spine dysplasia, scoliosis, spatula-shaped distal phalanges and distinctive craniofacial abnormalities, including cleft palate.

334
(72.6%)

Thalidomide embryopathy

Aplasia/Hypoplasia of the thumb Aplasia/Hypoplasia of the ulna Chronic rhinitis Radial club hand

Thalidomide embryopathy is a group of anomalies presented in infants as a result of in utero exposure (between 20-36 days after fertilization) to thalidomide, a sedative used in treatment of a range of conditions, including morning sickness, leprosy and multiple myeloma (see these terms). Thalidomine embryopathy is characterized by phocomelia, amelia, forelimb and hand plate anomalies (absence of humerus and/or forearm, femur and/or lower leg, thumb anomalies). Other anomalies include facial hemangiomas, and damages to ears (anotia, microtia), eyes (microphthalmia, anophthalmos, coloboma, strabismus), internal organs (kidney, heart, and gastrointestinal tract), genitalia, and heart. Infant mortality associated with thalidomide embryopathy is estimated to be as high as 40%. Thalidomide is contraindicated in pregnancy and pregnancy prevention is recommended in women under treatment.

335
(72.6%)

Distal monosomy 7q36

Clinodactyly of the 5th finger Micrognathia Non-midline cleft lip Upslanted palpebral fissure

Distal monosomy 7q36 is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the long arm of chromosome 7, with a highly variable phenotype typically characterized by holoprosencephaly, growth restriction, developmental delay, facial dysmorphism (facial clefts, prominent forehead, hypertelorism, low-set ears, flat and broad nasal bridge, large mouth), abnormal fingers and palm or sole creases, ocular abnormalities, and other congenital malformations (incl. genital anomalies and caudal deficiency sequence). Cardiopathies have been occasionally reported.

335
(72.6%)

Distal monosomy 10p

Clinodactyly of the 5th finger Downslanted palpebral fissures Micrognathia Non-midline cleft lip

Distal monosomy 10p is a rare chromosomal disorder in which the tip of the short arm (p arm) of chromosome 10 is deleted resulting in a variable phenotype depending on the size of the deletion. The deletion may involve only the terminal 10p15 band, or extend towards the centromere to bands 10p14 or 10p13.

335
(72.6%)

Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

Clinodactyly of the 5th finger Micrognathia Non-midline cleft lip Sparse eyelashes

Autosomal dominant inheritance

An ectodermal dysplasia syndrome with defining features of ankyloblepharon filiforme adnatum (AFA), ectodermal abnormalities and a cleft lip and/or palate.

338
(72.6%)

Achondrogenesis

Long philtrum Micrognathia Micromelia Short long bone

A rare group of lethal skeletal dysplasias characterized by an endochondral ossification deficiency that leads to dwarfism with extreme micromelia, a small thorax, a prominent abdomen, anasarca and polyhydramnios. There are three types of achondrogenesis that exist and that differ clinically, radiologically, histologically and genetically: achondrogensis type 1a, type 1b and type 2.

339
(72.5%)

Congenital absence/hypoplasia of fingers excluding thumb, unilateral

Abnormality of the metacarpal bones Short metacarpal Short thumb

Autosomal dominant inheritance

Congenital absence/hypoplasia of fingers excluding thumb, unilateral is a rare, non-syndromic, terminal transverse limb reduction defect characterized by unilateral absence of the terminal portions of digits 2 to 5, with a mildly hypoplastic thumb and small nail remnants on the digital stumps. Metacarpal bones may be variably reduced.

339
(72.5%)

Brachydactyly type A2

Short 2nd metacarpal Short foot Short middle phalanx of the 5th finger

Autosomal dominant inheritance

Brachydactyly type A2 (BDA2) is a congenital malformation characterized by shortening (hypoplasia or aplasia) of the middle phalanges of the index finger and, sometimes, of the little finger.

339
(72.5%)

Syndactyly type 5

Metacarpal synostosis Metatarsal synostosis Short distal phalanx of finger

Autosomal dominant inheritance

Syndactyly type 5 (SD5) is a very rare congenital limb malformation characterized by postaxial syndactyly of hands and feet, associated with metacarpal and metatarsal fusion of fourth and fifth digits.

339
(72.5%)

Coloboma of macula-brachydactyly type B syndrome

Broad thumb Renal agenesis Short distal phalanx of finger

Autosomal dominant inheritance

Coloboma of macula - brachydactyly type B or Sorsby syndrome is a malformation syndrome characterized by the combination of bilateral coloboma of macula with horizontal pendular nystagmus and severe visual loss, and brachydactyly type B (see these terms). The hand and feet defects comprise shortening of the middle and terminal phalanges of the second to fifth digits, hypoplastic or absent nails (congenital anonychia; see this term), broad or bifid thumbs and halluces, syndactyly and flexion deformities of the joints of some digits. Coloboma of macula - brachydactyly type B is inherited in a dominant manner.

339
(72.5%)

Brachydactyly type A5

Abnormality of the metacarpal bones Broad thumb Short middle phalanx of finger

Brachydactyly type A5 (BDA5) is a very rare congenital malformation of the digits characterized by absence of the middle phalanges (usually of digits 2 to 5), nail dysplasia and duplicated terminal phalanx of the thumb.

339
(72.5%)

Mesoaxial synostotic syndactyly with phalangeal reduction

Metacarpal synostosis Short palm Short thumb Toe syndactyly

Autosomal recessive inheritance

Mesoaxial synostotic syndactyly (MSSD) with phalangeal reduction is a novel and distinct form of non-syndromic syndactyly including complete syndactyly of the 3rd and 4th fingers with synostoses of the corresponding metacarpals and associated single phalanges, syndactyly of the 2nd and 3rd toes and 5th finger clinodactyly.

339
(72.5%)

Acromesomelic dysplasia, Hunter-Thompson type

Acromesomelia Brachydactyly Cuboidal metacarpal Short thumb

Autosomal recessive inheritance

A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism (adult height approximately 120 cm) with abnormalities limited to the limbs (affecting the lower limbs more than upper limbs, with middle and distal segments being the most affected), severe shortening, absence or fusion of tubular bones of hands and feet and large joint dislocations. As seen in acromesomelic dysplasia, Grebe type and acromesomelic dysplasia, Maroteaux type, facial features and intelligence are normal.

346
(72.4%)

Pentasomy X

Micrognathia Radioulnar synostosis Small hand Upslanted palpebral fissure Wide nasal bridge

Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX).

347
(72.4%)

Brachydactyly-preaxial hallux varus syndrome

Abnormal palate morphology Micrognathia Short metacarpal Short metatarsal Thick eyebrow

Autosomal dominant inheritance

Preaxial brachydactyly-hallux varus syndrome is characterized the association of hallux varus with short thumbs and first toes (involving the metacarpals, metatarsals, and distal phalanges; the proximal and middle phalanges are of normal length) and abduction of the affected digits.

348
(72.4%)

Hydrolethalus

Broad thumb Cleft palate Micrognathia Postaxial hand polydactyly Unilateral cleft lip

Hydrolethalus (HLS) is a severe fetal malformation syndrome characterized by craniofacial dysmorphic features, central nervous system, cardiac, respiratory tract and limb abnormalities.

349
(72.4%)

Mietens syndrome

High forehead Hypoplasia of the radius Hypoplasia of the ulna

Autosomal recessive inheritance

Mietens syndrome is a very rare syndrome consisting of corneal opacity, nystagmus, strabismus, flexion contracture of the elbows with dislocation of the head of the radius and abnormally short ulnae and radii.

349
(72.4%)

Léri-Weill dyschondrosteosis

Hypoplasia of the radius Hypoplasia of the ulna Micromelia Wide nasal bridge

Autosomal dominant inheritance

A rare skeletal dysplasia marked by disproportionate short stature and the characteristic Madelung wrist deformity.

351
(72.3%)

Charlie M syndrome

Abnormality of the metacarpal bones Brachydactyly Micrognathia Narrow mouth Non-midline cleft lip

Charlie M syndrome is a rare bone developmental disorder which belongs to a group of oromandibular limb hypogenesis syndromes that includes hypoglossia-hypodactyly and glossopalatine ankylosis (see these terms). The major anomalies which occur commonly in this group are hypoplasia of the mandible, syndactyly and ectrodactyly, small mouth, cleft palate, hypodontia, and facial paralysis. Patients with Charlie M syndrome also present with hypertelorism, absent or conically crowned incisors, and variable degrees of hypodactyly of the hands and feet. There have been no further descriptions in the literature since 1976.

352
(72.3%)

Orofaciodigital syndrome type 4

Abnormality of the tongue Aplasia/Hypoplasia of the tibia Median cleft lip Micrognathia Micromelia

Autosomal recessive inheritance

Oral-facial-digital syndrome, type 4 is characterized by lingual hamartoma, postaxial polysyndactyly of hands and feet, and mesomelic shortening of the legs with supinate equinovarus feet.

353
(72.2%)

Intellectual disability-polydactyly-uncombable hair syndrome

Abnormal palate morphology Aplasia/Hypoplasia of fingers Micrognathia Upslanted palpebral fissure

Intellectual disability-polydactyly-uncombable hair syndrome is a multiple congenital anomalies/dysmorphic syndrome characterized by intellectual disability, postaxial polydactyly, phalangeal hypoplasia, 2-3 toe syndactyly, uncombable hair and facial dysmorphism (including frontal bossing, hypotelorism, narrow palpebral fissures, nasal bridge and lips, prominent nasal root, large abnormal ears with prominent antihelix, poorly folded helix, underdeveloped lobule and antitragus, and micrognathia evolving into prognatism). Cryptorchidism, conductive hearing loss and progressive thoracic kyphosis were also reported.

354
(72.2%)

Primary pulmonary hypoplasia

Cleft palate Epicanthus Micrognathia Patellar hypoplasia

Autosomal recessive inheritance

Primary pulmonary hypoplasia is a rare, isolated, genetic developmental defect during embryogenesis characterized by congenital malformation of pulmonary parenchyma with absence of other anomalies. Neonatally patients present with decreased breath sounds, small lung volume and severe respiratory distress that is not responsive to aggressive treatment (including surfactant instillation/ mechanical respiratory support). It is usually not compatible with life.

354
(72.2%)

Mosaic trisomy 8

Blepharophimosis Cleft palate Micrognathia Patellar aplasia

Mosaic trisomy 8 is a chromosomal disorder defined by the presence of three copies of chromosome 8 in some cells of the organism. It is characterized by facial dysmorphism, mild intellectual deficit and joint, urinary, cardiac and skeletal anomalies.

356
(72.2%)

Severe intellectual disability-epilepsy-anal anomalies-distal phalangeal hypoplasia

Aplasia/Hypoplasia of the distal phalanges of the toes Highly arched eyebrow Mandibular prognathia Short philtrum

Severe intellectual disability-epilepsy-anal anomalies-distal phalangeal hypoplasia is characterised by severe intellectual deficit, epilepsy, hypoplasia of the terminal phalanges, and an anteriorly displaced anus. It has been described in two sisters born to consanguineous parents. The syndrome is transmitted as an autosomal recessive trait and appears to be caused by anomalies in to chromosome regions, one localised to chromosome 1 and the other to chromosome 14.

357
(72.2%)

Van der Woude syndrome

Cleft upper lip Epicanthus Syndactyly Temporomandibular joint ankylosis

Van der Woude syndrome (VWS) is a rare congenital genetic dysmorphic syndrome characterized by paramedian lower-lip fistulae, cleft lip with or without cleft palate, or isolated cleft palate.

358
(72.1%)

Microbrachycephaly-ptosis-cleft lip syndrome

Malar flattening Mandibular prognathia Short palm Unilateral cleft lip

Autosomal recessive inheritance

Microbrachycephaly-ptosis-cleft lip syndrome is characterised by the association of intellectual deficit, microbrachycephaly, hypotelorism, palpebral ptosis, a thin/long face, cleft lip, and anomalies of the lumbar vertebra, sacrum and pelvis. It has been described in two Brazilian sisters. Transmission appears to be autosomal recessive.

359
(72.1%)

Rubinstein-Taybi syndrome

Abnormality of the dentition Brachydactyly Broad thumb Epicanthus Micrognathia

A rare malformation syndrome characterized by congenital anomalies (microcephaly, specific facial characteristics, broad thumbs and halluces and postnatal growth retardation), short stature, intellectual disability and behavioural characteristics.

359
(72.1%)

Situs inversus totalis

Aglossia Blepharophimosis Brachydactyly Broad thumb Micrognathia

Autosomal dominant inheritance Autosomal recessive inheritance

A rare, genetic, developmental defect during embryogenesis characterized by total mirror-image transposition of both thoracic and abdominal viscera across the left-right axis of the body. Congenital abnormalities, such as primary ciliary dyskinesia, Kartagener type, polysplenia syndrome, biliary atresia, congenital heart disease, and midgut malrotation, as well as vascular anomalies (e.g. absence of retrohepatic inferior vena cava, preduodenal portal vein, aberrant hepatic arterial anatomy) and malignancy, are frequently associated.

361
(72.1%)

Mosaic trisomy 9

Cleft palate Finger clinodactyly Micrognathia Micromelia Telecanthus

Mosaic trisomy 9 is a rare chromosomal anomaly syndrome, with a highly variable phenotype, principally characterized by intellectual disability, growth and developmental delay, facial dysmorphism (incl. microphthalmia, deep-set eyes, low-set, malformed ears, bulbous nose, high-arched palate, micrognathia) and congenital heart defects (e.g. ventricular septal defect), as well as urogenital (e.g. hypoplastic genitalia, cryptorchidism), skeletal (congenital joint dislocations or hyperflexion, scoliosis/kyphosis) and central nervous system anomalies (hydrocephalus, Dandy-Walker malformation). Pigmentary mosaic skin lesions along the lines of Blaschko are also frequently observed.

361
(72.1%)

Marfan syndrome

Arachnodactyly Cleft palate Downslanted palpebral fissures Micrognathia Rhizomelia

Autosomal dominant inheritance

Marfan syndrome is a systemic disease of connective tissue characterized by a variable combination of cardiovascular, musculo-skeletal, ophthalmic and pulmonary manifestations.

363
(72.1%)

Megalocornea-intellectual disability syndrome

Epicanthus Genu varum Micrognathia Short philtrum Tapered finger

Autosomal recessive inheritance

Megalocornea-intellectual disability syndrome is a rare intellectual disability syndrome most commonly characterized by megalocornea, congenital hypotonia, varying degrees of intellectual disability, psychomotor/developmental delay, seizures, and mild facial dysmorphism (including round face, frontal bossing, antimongoloid slant of the eyes, epicanthal folds, large low set ears, broad nasal base, anteverted nostrils, and long upper lip). Interfamilial and intrafamilial clinical variability has been reported.

363
(72.1%)

Cohen syndrome

Abnormal eyelid morphology Arachnodactyly Genu valgum Micrognathia Short philtrum

Autosomal recessive inheritance

Cohen syndrome (CS) is a rare genetic developmental disorder characterized by microcephaly, characteristic facial features, hypotonia, non-progressive intellectual deficit, myopia and retinal dystrophy, neutropenia and truncal obesity.

365
(72.1%)

Multiple epiphyseal dysplasia, Lowry type

Cleft palate Micrognathia Rhizomelia Upslanted palpebral fissure

Sporadic

Multiple epiphyseal dysplasia, Lowry type is a rare primary bone dysplasia characterized by small, flat epiphyses (esp. the capital femoral epiphyses), rhizomelic shortening of limbs, cleft of secondary palate, micrognathia, mild joint contractures and facial dysmorphism (incl. mildly upward-slanting palpebral fissures, hypertelorism, broad nasal tip). Additionally reported features include scoliosis, genu valgum, mild pectus excavatum, platyspondyly, dislocated radial heads, brachydactyly, hypoplastic fibulae and talipes equinovarus.

365
(72.1%)

Desmosterolosis

Cleft palate Epicanthus Micrognathia Micromelia

Autosomal recessive inheritance

Desmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.

367
(72.0%)

Aymé-Gripp syndrome

Downslanted palpebral fissures Large fontanelles Radioulnar synostosis Tapered finger Thin upper lip vermilion

Autosomal recessive inheritance Sporadic

Fine-Lubinsky syndrome is characterised by psychomotor delay, brachycephaly with flat face, small nose, microstomia, cleft palate, cataract, hearing loss, hypoplastic scrotum and digital anomalies.

368
(72.0%)

Pfeiffer syndrome

Brachydactyly Broad thumb Mandibular prognathia Open mouth Short philtrum

Autosomal dominant inheritance

Pfeiffer syndrome (PS) is a common form of acrocephalosyndactyly (see this term), a group of inherited congenital malformation disorders, characterized by variable degrees of bicoronal craniosynostosis, variable hand and foot malformations and various other associated manifestations.

369
(71.9%)

Angelman syndrome

Brachydactyly Mandibular prognathia Unilateral cleft lip Wide mouth

Autosomal dominant inheritance Sporadic

A neurogenetic disorder characterized by severe intellectual deficit and distinct facial dysmorphic features.

370
(71.9%)

RIN2 syndrome

Brachydactyly Downslanted palpebral fissures Long philtrum Macrocephaly

Autosomal recessive inheritance

RIN2 syndrome, formerly known as macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome, is a very rare inherited connective tissue disorder characterized by macrocephaly, sparse scalp hair, soft-redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rarer manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly (see this term) have also been reported.

371
(71.8%)

Harlequin ichthyosis

Eclabion Ectropion Short foot

Autosomal recessive inheritance

Harlequin ichthyosis (HI) is the most severe variant of autosomal recessive congenital ichthyosis (ARCI; see this term). It is characterized at birth by the presence of large, thick, plate-like scales over the whole body associated with severe ectropion, eclabium, and flattened ears, that later develops into a severe scaling erythroderma.

371
(71.8%)

Multiple endocrine neoplasia type 2

Abnormal eyelid morphology Patellar aplasia Thick lower lip vermilion

Multiple endocrine neoplasia type 2 (MEN2) is a multiple endocrine neoplasia (see this term), a polyglandular cancer syndrome characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma (PCC; see these terms), in one variant, primary hyperparathyroidism (PHPT). There are three forms: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC) (see these terms).

373
(71.8%)

Autosomal dominant popliteal pterygium syndrome

Ankyloblepharon Micrognathia Non-midline cleft lip Split hand

Autosomal dominant inheritance

A rare genetic malformative disorder characterized by cleft lip, with or without cleft palate, contractures of the lower extremities, abnormal external genitalia, syndactyly of fingers and/or toes, and a pyramidal skin fold over the hallux nail.

373
(71.8%)

Zlotogora-Ogur syndrome

Cleft upper lip Downslanted palpebral fissures Micrognathia Palmoplantar hyperkeratosis

Autosomal recessive inheritance

Zlotogora-Ogur syndrome is an ectodermal dysplasia syndrome characterized by hair, skin and teeth anomalies, facial dysmophism with cleft lip and palate, cutaneous syndactyly and, in some cases, intellectual disability.

375
(71.8%)

Ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome

Clinodactyly of the 5th finger Long philtrum Microretrognathia Telecanthus

Ptosis - upper ocular movement limitation - absence of lacrimal punctum is a recently described association of absence of the lower lid lacrimal punctum, bilateral ptosis, elevation deficiency of both eyes and mild facial dysmorphism.

375
(71.8%)

Toluene embryopathy

Epicanthus Micrognathia Smooth philtrum Tapered finger

A neurodevelopmental teratologic syndrome due to prenatal exposure to toluene. The disease is characterized by prematurity, low birth weight, dysmorphic features (short palpebral fissures, deep set eyes, low set ears, mid-facial hypoplasia, flat nasal bridge, thin upper lip, micrognathia, spatulate fingertips and small fingernails), central nervous system dysfunctions (intellectual disability, microcephaly, language impairment, hyperactivity, visual dysfunction) and postnatal growth delay. Prenatal exposure to toluene occurs as a result of incidental occupational exposure or solvent abuse during pregnancy. The features of toluene embryopathy often overlap with those seen in fetal alcohol syndrome.

375
(71.8%)

17q21.31 microduplication syndrome

Clinodactyly of the 5th finger Epicanthus Micrognathia Short philtrum

The newly described 17q21.31 microduplication syndrome is associated with a broad clinical spectrum, of which behavioral disorders and poor social interaction seem to be the most consistent.

375
(71.8%)

Non-distal trisomy 13q

Abnormal eyelash morphology Long philtrum Micrognathia Postaxial hand polydactyly

Non-distal trisomy 13q is a rare chromosomal anomaly disorder, resulting from the partial duplication of the proximal long arm of chromosome 13, with a highly variable phenotype principally characterized by increased polymorphonuclear leucocyte projections and persistence of fetal hemoglobin, as well as growth and developmental delay and craniofacial dysmorphism (incl. microcephaly, depressed nasal bridge, stubby nose, low-set, malformed ears, cleft lip/palate, micrognathia). Strabismus, clinodactyly and undescended testes in males may also be associated.

375
(71.8%)

Craniofacial dyssynostosis

Clinodactyly of the 5th finger Epicanthus Micrognathia Short philtrum

Autosomal recessive inheritance Sporadic

Craniofacial dyssynostosis (CFD) is a rare cranial malformation syndrome characterized by the premature closure of both lambdoid sutures and the posterior sagittal suture, resulting in abnormal skull contour (frontal bossing, anterior turricephaly with mild brachycephaly, biparietal narrowing, occipital concavity) and dysmorphic facial features (low-set ears, midfacial hypoplasia). Short stature, developmental delay, epilepsy, and oculomotor dyspraxia have also been reported. Associated anomalies include enlargement of the cerebral ventricles, agenesis of the corpus callosum, Arnold-Chiari malformation type I (see this term), venous anomalies of skull and hydrocephalus.

375
(71.8%)

Flat face-microstomia-ear anomaly syndrome

Camptodactyly of finger Long philtrum Micrognathia Telecanthus

Autosomal dominant inheritance

Flat face-microstomia-ear anomaly syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by dysmorphic facial features, including high forehead, elongated and flattened midface, arched and sparse eyebrows, short palpebral fissures, telecanthus, long nose with hypoplastic nostrils, long philtrum, high and narrow palate and microstomia with downturned corners. Ears are characteristically malformed, large, low-set and posteriorly rotated and nasal speech is associated. There have been no further descriptions in the literature since 1994.

375
(71.8%)

Fallot complex-intellectual disability-growth delay syndrome

Clubbing of fingers Downslanted palpebral fissures Micrognathia Thin upper lip vermilion

Autosomal recessive inheritance

Fallot complex - intellectual deficit - growth delay is a rare disorder characterized by tetralogy of Fallot, minor facial anomalies, and severe intellectual deficiency and growth delay.

375
(71.8%)

Ring chromosome 10 syndrome

Downslanted palpebral fissures Long philtrum Micrognathia Tapered finger

An autosomal anomaly characterized by variable clinical features, depending on the size and precise location of deleted chromosome segments. Most patients present with developmental delay, intellectual disability, growth retardation, microcephaly, clinodactyly, and dysmorphic features. Congenital heart disease and genitourinary anomalies were reported in some cases.

375
(71.8%)

Miller-Dieker syndrome

Abnormality of upper lip Clinodactyly of the 5th finger Epicanthus Micrognathia

Autosomal dominant inheritance Contiguous gene syndrome

Miller-Dieker Syndrome (MDS) is a contiguous gene deletion syndrome of chromosome 17p13.3, characterised by classical lissencephaly (lissencephaly type 1) and distinct facial features. Additional congenital malformations can be part of the condition.

375
(71.8%)

Cardiocranial syndrome, Pfeiffer type

Broad philtrum Downslanted palpebral fissures Micrognathia Slender finger

Autosomal dominant inheritance Autosomal recessive inheritance

Pfeiffer-type cardiocranial syndrome is an extremely rare disorder recognized in less than ten patients worldwide and characterized by a congenital heart defect, sagittal craniosynostosis and severe developmental delay (growth retardation and intellectual deficit).

375
(71.8%)

6q25 microdeletion syndrome

Clinodactyly of the 5th finger Epicanthus Long philtrum Micrognathia

6q25 microdeletion syndrome is a recently described syndrome characterized by developmental delay, facial dysmorphism and hearing loss.

375
(71.8%)

Global developmental delay-osteopenia-ectodermal defect syndrome

Clinodactyly of the 2nd finger Epicanthus Long philtrum Micrognathia

This syndrome is characterised by the association of global developmental delay, osteopenia and skin anomalies.

375
(71.8%)

Müllerian derivatives-lymphangiectasia-polydactyly syndrome

Downslanted palpebral fissures Micrognathia Postaxial hand polydactyly Thin upper lip vermilion

Autosomal recessive inheritance

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

375
(71.8%)

Oculocerebrofacial syndrome, Kaufman type

Abnormality of upper lip Arachnodactyly Epicanthus Micrognathia

Autosomal recessive inheritance

Oculocerebrofacial syndrome, Kaufman type is characterized by psychomotor retardation, microcephaly, upslanting palpebral fissures, eye abnormalities (microcornea, strabismus, myopia, optic atrophy), high-arched palate, preauricular skin tags and micrognathia with respiratory distress. It has been described in about 10 cases. Other anomalies can be present: long thin hands and feet, ambiguous genitalia, hypertelorism, etc. An autosomal recessive mode of inheritance seems most likely.

375
(71.8%)

Distal monosomy 3p

Epicanthus Long philtrum Micrognathia Postaxial hand polydactyly

Autosomal dominant inheritance

Distal monosomy 3p is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the short arm of chromosome 3, with a highly variable phenotype typically characterized by pre- and post-natal growth retardation, intellectual disability, developmental delay and craniofacial dysmorphism (microcephaly, trigonocephaly, downslanting palpebral fissures, telecanthus, ptosis, micrognathia). Postaxial polydactyly, hypotonia, renal anomalies and congenital heart defects (e.g. atrioventricular septal defect) may be associated.

375
(71.8%)

16q24.3 microdeletion syndrome

Micrognathia Proximal placement of thumb Smooth philtrum Upslanted palpebral fissure

16q24.3 microdeletion syndrome is a recently described syndrome associated with variable developmental delay, facial dysmorphism, seizures and autistic spectrum disorder.

375
(71.8%)

Lathosterolosis

Epicanthus Long philtrum Micrognathia Postaxial hand polydactyly

Autosomal recessive inheritance

Lathosterolosis is an extremely rare inborn error of sterol biosynthesis characterized by facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease.

375
(71.8%)

Distal 22q11.2 microduplication syndrome

Epicanthus Micrognathia Smooth philtrum Tapered finger

Distal 22q11.2 microduplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 22, with a highly variable phenotype principally characterized by developmental delay, intellectual disability, hypotonia, growth retardation, velopharyngeal insufficiency, mild craniofacial dysmorphism (microcephaly, tall/broad forehead, small downslating palpebral fissures, hooded eyelids, flat nasal bridge, low posterior hairline) and digital anomalies. Congenital heart malformations, visual and hearing impairment, urogenital abnormalities, behavourial problems and seizures have also been reported.

375
(71.8%)

Baraitser-Winter cerebrofrontofacial syndrome

Duplication of thumb phalanx Epicanthus Long philtrum Micrognathia

Baraitser-Winter syndrome (BWS) is a malformation syndrome, characterized by facial dysmorphism (hypertelorism with ptosis, broad bulbous nose, ridged metopic suture, arched eyebrows, progressive coarsening of the face), ocular coloboma, pachygyria and/or band heterotopias with antero-posterior gradient, progressive joint stiffening, and intellectual deficit of variable severity, often with severe epilepsy. Pachygyria - epilepsy - intellectual disability - dysmorphism (Fryns-Aftimos syndrome (FA); see this term) corresponds to the appearance of BWS in elderly patients.

375
(71.8%)

Trisomy 17p

Downslanted palpebral fissures Micrognathia Smooth philtrum Tapered finger

Trisomy 17p is a rare chromosomal abnormality resulting from the duplication of the short arm of chromosome 17 and characterized by pre- and post-natal growth retardation, developmental delay, hypotonia, digital abnormalities, congenital heart defects, and distinctive facial features.

375
(71.8%)

Monosomy 9p

Epicanthus Long philtrum Micrognathia Postaxial hand polydactyly

Autosomal dominant inheritance Sporadic

Monosomy 9p is a rare chromosomal anomaly characterized by psychomotor developmental delay, facial dysmorphism (trigonocephaly, midface hypoplasia, upslanting palpebral fissures, dysplastic small ears, flat nasal bridge with anteverted nostrils and long philtrum, micrognathia, choanal atresia, short neck), single umbilical artery, omphalocele, inguinal or umbilical hernia, genital abnormalities (hypospadia, cryptorchidism), muscular hypotonia and scoliosis.

375
(71.8%)

FG syndrome type 1

Abnormal thumb morphology Downslanted palpebral fissures Long philtrum Micrognathia

X-linked recessive inheritance

375
(71.8%)

7q11.23 microduplication syndrome

Long eyelashes Long fingers Micrognathia Thin upper lip vermilion

Autosomal dominant inheritance

7q11.23 microduplication syndrome is a rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 7 characterized by a highly variable phenotype that typically manifests with mild-moderate intellectual delay (patients could be in the normal range), speech disorders (particularly of expressive language), and distinctive craniofacial features (brachycephaly, broad forehead, straight eyebows, broad nasal tip, short philtrum, thin upper lip and facial asymmetry). Hypotonia, developmental coordination disorders, behavioral problems (such as anxiety, ADHD and oppositional disorders) and various congenital anomalies, such as heart defects, diaphragmatic hernia, renal malformations and cryptorchidism, are frequently presented. Neurological abnormalities (visible on MRI) have been reported.

375
(71.8%)

22q11.2 deletion syndrome

Epicanthus Hand polydactyly Micrognathia Short philtrum

22q11.2 deletion syndrome (DS) is a chromosomal anomaly which causes a congenital malformation disorder whose common features include cardiac defects, palatal anomalies, facial dysmorphism, developmental delay and immune deficiency.

399
(71.7%)

Ossification anomalies-psychomotor developmental delay syndrome

Micrognathia Shallow orbits Short 5th finger Triangular face

Ossification anomalies-psychomotor developmental delay syndrome is characterised by hypomineralisation of the cranial bones, thoracic dystrophy, hypotonia, and abnormal and slender long bones due to an alteration in remodelling during ossification.

400
(71.7%)

Acrorenal syndrome

Abnormality of the ulna Aplasia/Hypoplasia of the radius Cleft palate Micrognathia

Autosomal recessive inheritance

A spectrum of congenital malformative disorders characterized by the co-occurrence of distal limb anomalies (usually bilateral cleft feet and/or hands) and renal defects (e.g. unilateral or bilateral agenesis), that can be associated with a variety of other anomalies such as those of genitourinary tract (genital anomalies, ureteral hypoplasias, vesicoureteral reflux), abdominal well defects, intestinal atresias, and lung malformations. Familial cases have been reported in which an autosomal recessive inheritance was suspected.