201
(75.2%)

1p36 deletion syndrome

11 pairs of ribs Brachydactyly Epicanthus Long philtrum Short foot

Sporadic

1p36 deletion syndrome is a chromosomal anomaly characterized by distinctive facial dysmorphic features, hypotonia, developmental delay, intellectual disability, seizures, heart defects, hearing impairment and prenatal onset growth deficiency.

202
(75.2%)

Ulnar/fibula ray defect-brachydactyly syndrome

Aplasia/Hypoplasia of the ulna Malar flattening Short 5th finger Short foot

Autosomal dominant inheritance

Ulnar/fibula ray defect - brachydactyly syndrome is a very rare malformation syndrome characterized by ulnar hypoplasia associated with hypoplastic to absent fourth and/or fifth digits, fibular hypoplasia, short stature and facial dysmorphism.

203
(75.2%)

CHST3-related skeletal dysplasia

Highly arched eyebrow Long philtrum Rhizomelia Short metacarpal

Autosomal recessive inheritance

CHST3-related skeletal dysplasia is a very rare bone disorder characterized clinically by short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; limitation of range of motion of large joints; progressive kyphosis; and occasional scoliosis. In a few patients, minor heart valve dysplasia has also been described. Intellect, vision and hearing are normal.

204
(75.2%)

Osteogenesis imperfecta

Brachydactyly Median cleft lip Micrognathia Short long bone

Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity.

205
(75.2%)

Microtriplication 11q24.1

Long eyelashes Short foot Small hand Smooth philtrum

Microtriplication 11q24.1 is an extremely rare partial autosomal tetrasomy, resulting from a partial triplication of the long arm of chromosome 11, characterized by intellectual disability (with severe verbal impairment), short stature with small extremities, keratoconus and distinctive facial features (round, course face, upward slanting palpebral fissures, mild synophris, large nose with thick ala nasi and triangular tip, large mouth with broad lips, short and smooth philtrum, large protruded chin, ears with adherent lobules). Additionally, patients are overweight and present hypercholesterolemia.

205
(75.2%)

X-linked intellectual disability, Cabezas type

Epicanthus Short foot Short palm Short philtrum

X-linked recessive inheritance

An X-linked syndromic intellectual disability characterized by developmental delay, intellectual disability with significant speech impairment, and short stature in male patients. Variable additional clinical features have been associated, including macrocephaly, seizures, tremor, gait abnormalities, hypogonadism, truncal obesity, behavioral disturbances and unspecific facial dysmorphism.

205
(75.2%)

Hypertelorism, Teebi type

Downslanted palpebral fissures Long philtrum Short toe Small hand

Autosomal dominant inheritance

Teebi type hypertelorism is a rare genetic disease characterized by hypertelorism with facial features that can closely resemble craniofrontonasal dysplasia (see this term), such as prominent forehead, widow's peak, heavy and broad eyebrows, long palpebral fissures, ptosis, high and broad nasal bridge, short nose, low-set ears, natal teeth, thin upper lip and a grooved chin, as well as limb (i.e. fifth-finger clinodactyly, pes adductus, mild interdigital webbing), urogenital (i.e. bilateral cryptorchidism and shawl scrotum in males) and umbilical (i.e. hernia/small omphalocele) anomalies and cardiac (i.e. ventricular or atrial septal defect, patent ductus arteriosus) defects. Additional findings such as polycystic kidneys and iridochorioretinal colobomas have also been reported and psychomotor development is normal. The facial features can also resemble Aarskog and Opitz G/BBB syndromes (see these terms).

205
(75.2%)

19p13.12 microdeletion syndrome

Epicanthus Long philtrum Short palm

19p13.12 microdeletion syndrome is a newly described syndrome characterized by moderate to severe developmental delay, language delay, bilateral sensorineural and/or conductive hearing loss and facial dysmorphism.

209
(75.1%)

8p23.1 microdeletion syndrome

Broad thumb Epicanthus Micrognathia Tapered finger Thin vermilion border

8p23.1 deletion involves a partial deletion of the short arm of chromosome 8 characterized by low birth weight, postnatal growth deficiency, mild intellectual deficit, hyperactivity, craniofacial abnormalities, and congenital heart defects.

210
(75.1%)

1q21.1 microdeletion syndrome

Broad thumb Epicanthus Long philtrum Short foot

Autosomal dominant inheritance Sporadic

1q21.1 microdeletion syndrome is a newly described recurrent deletion syndrome with variable clinical manifestations but without the clinical picture of thrombocytopenia - absent radius (TAR) syndrome.

211
(75.0%)

CHAND syndrome

Ankyloblepharon Commissural lip pit Short fifth metatarsal

Autosomal recessive inheritance

212
(75.0%)

Autosomal recessive multiple pterygium syndrome

Epicanthus Long philtrum Micrognathia Patellar aplasia

Autosomal recessive inheritance

213
(75.0%)

Madelung deformity

Hypoplasia of the radius Micromelia Nephropathy Short 4th metacarpal

Madelung disease, or deformity (MD) is a predominantly bilateral wrist anomaly characterized by shortened and bowed radii and long ulnae leading to dorsal dislocation of the distal ulna and limited mobility of the wrist and elbow.

214
(74.9%)

Spondyloepiphyseal dysplasia, Nishimura type

Epicanthus Hemiatrophy of upper limb Long philtrum Micrognathia Slender finger

Autosomal recessive inheritance

Spondyloepiphyseal dysplasia Nishimura type is characterized by spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate and intellectual deficit.

214
(74.9%)

Distal trisomy 17q

Epicanthus Hand polydactyly Micrognathia Rhizomelia Thin upper lip vermilion

Distal trisomy 17q is a rare chromosomal anomaly syndrome with variable phenotype principally characterized by intellectual disability, developmental delay, short stature, craniofacial dysmorphism (incl. microcephaly, low posterior hairline, frontal bossing, bitemporal narrowing, low-set and malformed ears, flat nasal bridge, long philtrum, wide mouth with downturned corners, thin upper lip) and a short, webbed neck, as well as skeletal anomalies (e.g. brachyrhizomelia, poly-/syndactyly) and joint hyperlaxity. Cardiac, cerebral, and urogenital anomalies are also frequently associated.

216
(74.9%)

Schwartz-Jampel syndrome

Blepharophimosis Long philtrum Micrognathia Micromelia

Autosomal recessive inheritance

A rare syndrome characterised by myotonia and osteoarticular abnormalities.

217
(74.9%)

Spondyloepimetaphyseal dysplasia, Irapa type

Micromelia Pectus carinatum Short palm Upper limb undergrowth

Autosomal recessive inheritance

Spondyloepimetaphyseal dysplasia, Irapa type is characterized by disproportionate short-trunked short stature, pectus carinatum, short arms, short and broad hands, short metatarsals, flat and broad feet, coxa vara, genu valgum, osteoarthritis, arthrosis and moderate-to-serious gait impairment.

218
(74.9%)

Ellis Van Creveld syndrome

Abnormality of the dentition Micromelia Short distal phalanx of finger Short ribs Thin vermilion border

Autosomal recessive inheritance

Ellis-van Creveld syndrome (EVC) is a skeletal and ectoderlam dysplasia characterized by a tetrad of short stature, postaxial polydactyly, ectodermal dysplasia, and congenital heart defects.

219
(74.9%)

Atypical Werner syndrome

Aplasia/Hypoplasia of the eyebrow Micrognathia Short palm Thin vermilion border

An heterogeneous group of cases that are clinically diagnosed as Werner syndrome (WS) but do not carry WRN gene mutations. Similar to classical WS caused by WRN mutations, patients generally exhibit an aged appearance and common age-related disorders at earlier ages compared to the general population.

220
(74.8%)

Congenital glaucoma

Entropion Glossoptosis Micrognathia Short finger

A developmental glaucoma that results from the abnormal development of the aqueous drainage structure, characterized by an elevated intra-ocular pressure, enlargement of globe (buphthalmos), corneal edema and optic nerve cupping, and presenting clinically with the characteristic triad of epiphora, photophobia and blepharospasm.

221
(74.8%)

Maxillonasal dysplasia

Broad philtrum Cleft palate Retrognathia Short distal phalanx of finger

Autosomal dominant inheritance Autosomal recessive inheritance Heterogeneous Multifactorial inheritance

Binder syndrome is a rare developmental anomaly, affecting primarily the anterior part of the maxilla and nasal complex.

222
(74.7%)

Acrofacial dysostosis, Rodríguez type

Aplasia/Hypoplasia of the ulna Hand oligodactyly Malar flattening Microretrognathia

Autosomal recessive inheritance

A rare multiple malformative syndrome in which mandibulofacial dysostosis and severe limb reduction defects are associated with complex malformations of different organs and systems especially the CNS, urogenital tract, heart, and lungs. The mandibulofacial defect, characterized by extremely severe microretrognathism and cleft palate, causes death by respiratory distress. Limb reduction is severe and includes shoulder and pelvis hypoplasia, phocomelia with humerus hypoplasia, absent radius and ulna, complete absence of long bones of the legs, and various hand anomalies, predominantly preaxial reduction (absent thumbs). Other features include CNS malformations (agenesis of corpus callosum and acqueductal stenosis), lung anomalies (absent lung lobulation), complex cardiac malformations, and unicornis uterus. These infants also show facial dysmorphism and ear anomalies. The condition is a rare with an autosomal recessive mode of inheritance. The prognosis is poor and this condition leads to death in utero or shortly after birth.

223
(74.7%)

48,XXYY syndrome

Broad jaw Clinodactyly of the 5th finger Epicanthus Radioulnar synostosis Thick lower lip vermilion

A rare sex chromosome number anomaly disorder characterized, genetically, by the presence of an extra X and Y chromosome in males and, clinically, by tall stature, dysfunctional testes associated with infertility and insufficient testosterone production, cognitive, affective and social functioning impairments, global developmental delay, and an increased risk of congenital malformations.

224
(74.7%)

Early-onset seizures-distal limb anomalies-facial dysmorphism-global developmental delay syndrome

Arachnodactyly Broad thumb Downslanted palpebral fissures Retrognathia Thin upper lip vermilion

225
(74.7%)

20p12.3 microdeletion syndrome

Broad thumb Epicanthus Hypoplasia of the maxilla Long philtrum

20p12.3 microdeletion syndrome is a recently described syndrome characterized by Wolff-Parkinson-White syndrome (see this term), variable developmental delay and facial dysmorphism.

226
(74.6%)

Craniofrontonasal dysplasia

Brachydactyly Broad thumb Congenital pseudoarthrosis of the clavicle Downslanted palpebral fissures Oral cleft

X-linked dominant inheritance

Craniofrontonasal dysplasia is an X-linked malformation syndrome characterized by facial asymmetry (particularly orbital), body asymmetry, midline defects (hypertelorism, frontal bossing, broad grooved or bifid nasal tip, cleft lip and/or palate, high arched palate), skeletal anomalies (clavicle pseudoarthrosis, coronal craniosynostosis, various digital and limb anomalies including syndactyly, clinodactyly of the 5th finger, broad thumbs) and ectodermal dysplasias (dental anomalies, grooved nails, wiry hair). Contrary to most X-linked disorders, females are much more severely affected whereas males are asymptomatic or present with a mild phenotype, frequently only displaying hypertelorism.

227
(74.6%)

Frank-Ter Haar syndrome

Abnormality of the metacarpal bones Brachydactyly Downslanted palpebral fissures Mandibular prognathia Short philtrum

Autosomal recessive inheritance

Frank-ter Haar syndrome (formerly considered as an autosomal recessive form of Melnick-Needles syndrome; see this term) is defined by megalocornea, multiple skeletal anomalies, characteristic facial dysmorphism (wide fontanels, prominent forehead, hypertelorism, prominent eyes, full cheeks and micrognathia) and developmental delay.

228
(74.6%)

Intellectual disability-balding-patella luxation-acromicria syndrome

Acromesomelia Epicanthus Short toe Thin upper lip vermilion

X-linked recessive inheritance

Intellectual disability-balding-patella luxation-acromicria syndrome is characterised by severe intellectual deficit, patella luxations, acromicria, hypogonadism, facial dysmorphism (including midface hypoplasia and premature frontotemporal balding). It has been described in three unrelated males.

229
(74.5%)

Tetrasomy 18p

Epicanthus Large hands Long philtrum Retrognathia

Tetrasomy 18p is a very rare structural chromosomal anomaly affecting multiple body systems and characterized clinically by craniofacial abnormalities, delayed development, cognitive impairment, changes in muscle tone, distinctive facial features, and rarely renal malformations.

230
(74.5%)

16p11.2p12.2 microdeletion syndrome

Epicanthus Microretrognathia Oral cleft Short palm

Sporadic

16p11.2-p12.2 microdeletion syndrome is a recently described syndrome characterized by developmental delay and facial dysmorphism.

231
(74.5%)

Tetraploidy

Cleft palate Micrognathia Radial club hand Short philtrum

Tetraploidy is an extremely rare chromosomal anomaly, polyploidy, when an affected individual has four copies of each chromosome, instead of two, resulting in total of 92 chromosomes in each cell. The phenotype is severe with multiple congenital anomalies, including central nervous system, ocular, cardiac, renal, and/or genital malformations and limb defects. Most patients show severe intrauterine groth retardation, hypotonia, failure to thrive and developmental delay. It is usually associated with miscarriage.

232
(74.4%)

Microlissencephaly-micromelia syndrome

11 pairs of ribs Adducted thumb Long philtrum Micromelia Palpebral edema

Microlissencephaly-micromelia syndrome is a syndrome of abnormal cortical development, characterized by severe prenatal polyhydramnios, postnatal microcephaly, lissencephaly, upper limb micromelia, dysmorphic facies (coarse face, hypertrichosis, and short nose with long philtrum), intractable seizures, and early death. Hypoparathyroidism was noted in one case.

232
(74.4%)

Wiedemann-Steiner syndrome

Aplasia/Hypoplasia of the ribs Rhizomelia Tapered finger Telecanthus Thin upper lip vermilion

Autosomal dominant inheritance X-linked recessive inheritance

Wiedemann-Steiner syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by short stature, hypertrichosis cubiti, facial dysmorphism (hypertelorism, long eyelashes, thick eyebrows, downslanted, vertically narrow, long palpebral fissures, wide nasal bridge, broad nasal tip, long philtrum), developmental delay, and mild to moderate intellectual disability. It has a variable clinical phenotype with additional manifestations reported including muscular hypotonia, patent ductus arteriosus, small hands and feet, hypertrichosis on the back, behavioral difficulties, and seizures.

234
(74.4%)

Genitopalatocardiac syndrome

Brachydactyly Downslanted palpebral fissures Micrognathia Non-midline cleft lip

Autosomal recessive inheritance

Genitopalatocardiac syndrome is a rare, multiple congenital anomalies/dysmorphic syndrome characterized by male, 46,XY gonadal dysgenesis, cleft palate, micrognathia, conotruncal heart defects and unspecific skeletal, brain and kidney anomalies.

234
(74.4%)

Trisomy 8q

Brachydactyly Micrognathia Non-midline cleft lip Upslanted palpebral fissure

A partial autosomal trisomy characterized by developmental delay, intellectual disability, prenatal and postnatal growth retardation, congenital heart, genitourinary and skeletal anomalies, and dysmorphic facial features, including high and broad forehead, hypertelorism, upslanting palpebral fissures, broad nose, dysplastic and low set ears, micrognathia. Phenotypic features vary in relation to the duplication size.

234
(74.4%)

Trisomy 9p

Brachydactyly Epicanthus Micrognathia Non-midline cleft lip

Trisomy 9p is a rare chromosomal anomaly syndrome, resulting from a partial or complete trisomy of the short arm of chromosome 9, with a wide phenotypic variablility, typically characterized by intellectual disability, craniofacial dysmorphism (e.g. microcephaly, large anterior fontanel, hypertelorism, strabismus, downslanting palpebral fissures, malformed, low-set, protruding ears, bulbous nose, macrostomia, down-turned corners of mouth, micrognathia), digital anomalies (brachydactyly and clinodactyly), and short stature. Less frequently patients present with cardiopathy and renal, skeletal, and central nervous system malformations.

234
(74.4%)

Smith-Magenis syndrome

Brachydactyly Cleft upper lip Micrognathia Telecanthus

Autosomal dominant inheritance Sporadic

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by variable intellectual deficit, sleep disturbance, craniofacial and skeletal anomalies, psychiatric disorders, and speech and motor delay.

234
(74.4%)

Bifid uvula

Brachydactyly Microretrognathia Telecanthus Unilateral cleft lip

Autosomal dominant inheritance

Bifid uvula is a fissure type embryopathy affecting the uvula at the back of the soft palate.

239
(74.4%)

Oculoauriculovertebral spectrum with radial defects

Aplasia/Hypoplasia of the thumb Non-midline cleft lip Short mandibular rami Wide mouth

Autosomal dominant inheritance

Oculoauriculovertebral spectrum (OAVS) with radial defects is a rare branchial arches and limb primordia development disorder characterized by variable degrees of uni- or bilateral craniofacial malformation and radial defects that result in extremely variable phenotypic manifestations. Characteristic features include low postnatal weight, short stature, vertebral defects, hearing loss, and facial dysmorphism (incl. facial asymmetry, external, middle, and inner ear malformations, orofacial clefts, and mandibular hypoplasia). These features are invariably associated with radial defects, such as preaxial polydactyly, thumb and/or radius hypoplasia/agenesis, or triphalangeal thumb. Cardiac, pulmonary, renal, and central nervous system involvement has also been reported.

240
(74.4%)

EEC syndrome

Aplasia/Hypoplasia of the thumb Blepharitis Cleft lip

Autosomal recessive inheritance

EEC syndrome is a genetic developmental disorder characterized by ectrodactyly, ectodermal dysplasia, and orofacial clefts (cleft lip/palate).

241
(74.4%)

Bohring-Opitz syndrome

Cleft upper lip Retrognathia Short foot Upslanted palpebral fissure

Autosomal dominant inheritance Autosomal recessive inheritance

Bohring-Opitz syndrome is characterised by intrauterine growth retardation (IUGR), failure to thrive, facial dysmorphism (prominent metopic suture and forehead nevus flammeus, a low frontal and temporal hairline with hirsutism, puffy cheeks, upslanting palpebral fissures, exophthalmos, hypertelorism, cleft lip and palate, retrognathia and low set ears), flexion deformities of the elbows and wrists, camptodactyly, ulnar deviation of the fingers, foot anomalies and severe developmental delay. Less than 20 patients have been described so far. Although the large majority of reported cases occurred sporadically, autosomal recessive inheritance has also been reported.

242
(74.4%)

Marden-Walker syndrome

Arachnodactyly Blepharophimosis Cleft palate Micrognathia Radioulnar synostosis

Autosomal dominant inheritance Autosomal recessive inheritance

Marden-Walker syndrome (MWS) is a malformation syndrome characterized by multiple joint contractures (arthrogryposis), a mask-like face with blepharophimosis, micrognathia, high-arched or cleft palate, low-set ears, decreased muscular bulk, kyphoscoliosis and arachnodactyly.

243
(74.4%)

Lenz-Majewski hyperostotic dwarfism

Abnormal nasolacrimal system morphology Aplastic clavicle Short palm Thick vermilion border

Autosomal dominant inheritance Sporadic

An extremely rare syndrome associating dwarfism, characteristic facial appearance, cutis laxa and progressive bone sclerosis.

244
(74.3%)

Tall stature-intellectual disability-facial dysmorphism syndrome

Deep philtrum Mandibular prognathia Narrow palpebral fissure Short toe

Autosomal dominant inheritance

245
(74.3%)

Somatomammotropinoma

Cortical diaphyseal thickening of the upper limbs Large hands Mandibular prognathia Palpebral edema Thick lower lip vermilion

Somatomammotropinoma is a rare, mixed, functioning pituitary adenoma characterized by the cosecretion of growth hormone and prolactin, which manifests with signs and symptoms of both acromegaly and hyperprolactinemia.

246
(74.2%)

8q21.11 microdeletion syndrome

Abnormality of the metacarpal bones Camptodactyly of finger Epicanthus Micrognathia Short philtrum

Autosomal dominant inheritance Sporadic

8q21.11 microdeletion syndrome encompasses heterozygous overlapping microdeletions on chromosome 8q21.11 resulting in intellectual disability, facial dysmorphism comprising a round face, ptosis, short philtrum, Cupid's bow and prominent low-set ears, nasal speech and mild finger and toe anomalies.

247
(74.1%)

Histidinuria-renal tubular defect syndrome

Long philtrum Short middle phalanx of finger

248
(74.0%)

Abruzzo-Erickson syndrome

Brachydactyly Cleft palate Epicanthus Radioulnar synostosis Short toe

X-linked inheritance X-linked recessive inheritance

An orofacial clefting syndrome that is characterized by a cleft palate, ocular coloboma, hypospadias, mixed conductive-sensorineural hearing loss, short stature, and radio-ulnar synostosis.

249
(74.0%)

Absent radius-anogenital anomalies syndrome

Hypoplasia of the radius Rectovaginal fistula

X-linked inheritance

A rare, genetic limb reduction defects syndrome characterized by bilateral radial aplasia/hypoplasia manifesting with absent/short forearms in association with anogenital abnormalities (e.g. hypospadias or imperforate anus). Additional features reported include hydrocephalus and absent preaxial digits. There have been no further descriptions in the literature since 1993.

249
(74.0%)

Mesomelic dysplasia, Savarirayan type

Fibular aplasia Hypoplasia of proximal radius Intellectual disability

Autosomal dominant inheritance

Mesomelic dysplasia, Savarirayan type is characterised by severely hypoplastic and triangular-shaped tibiae, and absence of the fibulae. So far, two sporadic cases have been described. Moderate mesomelia of the upper limbs, proximal widening of the ulnas, pelvic anomalies and marked bilateral glenoid hypoplasia were also reported.

251
(74.0%)

Say-Barber-Miller syndrome

Micrognathia Patellar hypoplasia Thin vermilion border Upslanted palpebral fissure

Autosomal recessive inheritance

Say-Barber-Miller syndrome is characterised by the association of unusual facial features, microcephaly, developmental delay, and severe postnatal growth retardation.

252
(74.0%)

Ablepharon macrostomia syndrome

Camptodactyly of finger Cryptophthalmos Hypoplasia of the maxilla Thin vermilion border

Autosomal dominant inheritance Autosomal recessive inheritance

An extremely rare multiple congenital malformation syndrome characterized by the association of ablepharon, macrostomia, abnormal external ears, syndactyly of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations and developmental delay (in 2/3 of cases). Other reported manifestations include malar hypoplasia, absent or hypoplastic nipples, umbilical abnormalities and growth retardation. It is a mainly sporadic disorder, although a few familial cases having been reported, and it displays significant clinical overlap with Fraser syndrome.

253
(73.9%)

Brachydactyly type B

Cleft lip Short distal phalanx of finger Short foot Short metacarpal

Brachydactyly type B (BDB) is a very rare congenital malformation characterized by hypoplasia or aplasia of the terminal parts of fingers 2 to 5, with complete absence of the fingernails.

254
(73.9%)

20q13.33 microdeletion syndrome

Epicanthus Short lower limbs Smooth philtrum

20q13.33 is a rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 20 with a highly variable phenotype typically characterized by hypotonia, intellectual disability, cognitive and language deficits (including decreased or absent speech), pre and post-natal growth retardation, feeding difficulties, microcephaly, and malformed hands and feet. Neurodevelopmental disorders (including hyperactivity, social interactive problems and autism spectrum disorder), seizures and dysmorphic facial features (high forehead, hypertelorism, malformed ears, broad nasal bridge, bulbous nasal tip, thin upper lip, small chin) are frequently associated.

255
(73.9%)

Trichorhinophalangeal syndrome type 2

Aplasia/Hypoplasia of the mandible Brachydactyly Entropion Genu valgum Thin upper lip vermilion

Autosomal dominant inheritance

A very rare, genetic, multiple congenital anomaly disorder characterized by bone abnormalities, distinctive facial features, multiple exostoses, and intellectual disability.

256
(73.9%)

Myasthenia gravis

Cheilitis Hemiatrophy Micrognathia Upper eyelid retraction

Multifactorial inheritance

Myasthenia gravis (MG) is a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles.

257
(73.9%)

Retinoblastoma

Absent thumb Cleft palate Hemiatrophy Micrognathia Retinal astrocytic hamartoma

Autosomal dominant inheritance Somatic mutation Sporadic

A rare eye tumor disease representing the most common intraocular malignancy in children. It is a life threatening neoplasia but is potentially curable and it can be hereditary or non hereditary, unilateral or bilateral.

258
(73.8%)

45,X/46,XY mixed gonadal dysgenesis

Epicanthus High palate Micrognathia Short 4th metacarpal Short metatarsal

45,X/46,XY mixed gonadal dysgenesis (45,X/46,XY MGD) is a disorder of sex development (DSD) associated with a numerical sex chromosome abnormality resulting from Y-chromosome mosaicism and leading to abnormal gonadal development.

258
(73.8%)

Achondroplasia

Glossitis Micrognathia Short long bone Short metacarpal Telecanthus

Autosomal dominant inheritance

A form of chondrodysplasia, characterized by rhizomelia, exaggerated lumbar lordosis, brachydactyly, and macrocephaly with frontal bossing and midface hypoplasia.

260
(73.8%)

Brachydactyly-syndactyly, Zhao type

Short fifth metatarsal Short middle phalanx of the 5th finger Toe syndactyly

Autosomal dominant inheritance

Brachydactyly-syndactyly, Zhao type is a recently described syndrome associating a brachydactyly type A4 (short middle phalanges of the 2nd and 5th fingers and absence of middle phalanges of the 2nd to 5th toes) and a syndactyly of the 2nd and 3rd toes. Metacarpals and metatarsals anomalies are common.

260
(73.8%)

Brachydactyly type C

Abnormal fingernail morphology Short metatarsal Short middle phalanx of finger

Autosomal dominant inheritance Autosomal recessive inheritance

Brachydactyly type C (BDC) is a very rare congenital malformation characterized by brachymesophalangy of the index, middle and little fingers, with hyperphalangy of the index and middle finger and shortening of the 1st metacarpal. Only few families with BDC have been reported in the literature. The ring finger is usually the longest digit. Short metacarpals and symphalangism are occasionally present. Heterozygous mutations in the cartilage-derived morphogenetic protein 1, also known as growth/differentiation factor-5 gene (GDF5), have been reported in BDC patients. Many studies support an autosomal dominant mode of inheritance.

260
(73.8%)

Hand-foot-genital syndrome

Recurrent urinary tract infections Short first metatarsal Shortening of all middle phalanges of the fingers

Autosomal dominant inheritance

Hand-foot-genital syndrome (HFGS) is a very rare multiple congenital abnormality syndrome characterized by distal limb malformations and urogenital defects.

263
(73.8%)

Radioulnar synostosis-microcephaly-scoliosis syndrome

Abnormality of the philtrum Epicanthus Microcephaly Radioulnar synostosis Type A1 brachydactyly

Radioulnar synostosis-microcephaly-scoliosis syndrome, also known as Guiffré-Tsukahara syndrome, is an extremely rare syndrome characterized by the association of radioulnar synostosis with microcephaly, scoliosis, short stature and intellectual deficit.

264
(73.8%)

Johnson neuroectodermal syndrome

Everted lower lip vermilion Hand polydactyly Lower eyelid coloboma Microcephaly

Autosomal dominant inheritance

Johnson neuroectodermal syndrome is characterised by alopecia, anosmia or hyposmia, conductive deafness with malformed ears and microtia and/or atresia of the external auditory canal, and hypogonadotropic hypogonadism.

265
(73.8%)

Acitretin/etretinate embryopathy

Aplasia/hypoplasia involving bones of the upper limbs Epicanthus Median cleft palate Micrognathia

A rare teratogenic disorder due to acitretin or etretinate exposure during the first trimester of pregnancy, carrying a risk of fetal malformations of approximately 20%, including central nervous system, craniofacial, ear, thymic, cardiac and limb anomalies.

266
(73.8%)

2q23.1 microdeletion syndrome

Short palm Synophrys Tented upper lip vermilion

The newly described 2q23.1 microdeletion syndrome includes severe intellectual deficit with pronounced speech delay, behavioral abnormalities including hyperactivity and inappropriate laughter, short stature and seizures.

267
(73.7%)

Orofaciodigital syndrome type 6

Brachydactyly Central Y-shaped metacarpal Cleft palate Highly arched eyebrow Micrognathia

Autosomal recessive inheritance X-linked recessive inheritance

Joubert syndrome with orofaciodigital defect (or oral-facial-digital syndrome type 6, OFD6) is a very rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with orofacial anomalies and often polydactyly.

268
(73.7%)

PHAVER syndrome

Epicanthus Radioulnar synostosis Short thumb

Autosomal recessive inheritance

Phaver syndrome is a very rare syndrome characterized by the association of limb Pterygia, Heart anomalies, Autosomal recessive inheritance, Vertebral defects, Ear anomalies and Radial defects.

269
(73.7%)

Severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome

Broad thumb Lip pit Mandibular prognathia Tapered finger Telecanthus

Severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome is an extremely rare, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism, including microbrachycephaly, sloping forehead, micro/anophthalmia, large ears, prominent nasal root, mild micrognathia, and cleft palate, associated with cerebral palsy with choreoathetoid movements, intellectual disability, dextrocardia and longitudinal folding of plantae pedis. There have been no further descriptions in the literature since 1992.

270
(73.7%)

Anophthalmia plus syndrome

Bilateral cleft lip and palate Deviation of finger Eyelid coloboma Vertebral segmentation defect

Autosomal recessive inheritance

A very rare multiple congenital anomaly syndrome characterized by the presence of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities. An autosomal recessive inheritance has been suggested.

271
(73.7%)

Acromelic frontonasal dysplasia

Median cleft lip Patellar hypoplasia Telecanthus

Autosomal dominant inheritance

A rare frontonasal dysplasia characterized by distinct craniofacial (large fontanelle, hypertelorism, bifid nasal tip, nasal clefting, brachycephaly, median cleft face, carp-shaped mouth), brain (interhemispheric lipoma, agenesis of the corpus callosum), and limb (tibial hypoplasia/aplasia, club foot, symmetric preaxial polydactyly of the feet and bilateral clubbed and thickened nails of halluces) malformations as well as intellectual disability. Other manifestations sometimes reported include absent olfactory bulbs, hypopituitarism and cryptorchidism.

272
(73.6%)

MEND syndrome

Cleft palate Micrognathia Overlapping fingers Telecanthus

X-linked recessive inheritance

MEND syndrome is a rare, genetic, syndromic, sterol biosynthesis disorder affecting males characterized by skin manifestations, including collodion membrane, ichthyosis, and patchy hypopigmentary lesions, associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia) and craniofacial dysmorphism (large anterior fontanelle, telecanthus, hypertelorism, microphthalmia, prominent nasal bridge, low-set ears, micrognathia, cleft palate). 2,3 toe syndactyly, polydactyly, and kyphosis, as well as ophthalmic, cardiac and urogenital anomalies may also be associated.

272
(73.6%)

Trisomy 1q

Cleft palate Downslanted palpebral fissures Microretrognathia Overlapping fingers

Trisomy 1q is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 1, with a highly variable phenotype principally characterized by intellectual disability, short stature, craniofacial dysmorphism (incl. macro/microcephaly, prominent forehead, posteriorly rotated, low-set ears, abnormal palpebral fissures, microphthalmia, broad, flat nasal bridge, high-arched palate, micro/retrognathia), cardiac defects and urogenital anomalies. Patients may also present cerebral (e.g. ventriculomegaly) and gastrointestinal malformations, as well as dystonic tremor and recurrent respiratory tract infections.

274
(73.6%)

Short stature-wormian bones-dextrocardia syndrome

Abnormality of the philtrum Brachydactyly Downslanted palpebral fissures Micrognathia

A multiple congenital anomalies syndrome characterized by wormian bones, dextrocardia and short stature due to a growth hormone deficiency. Additional manifestations that have been reported include brachycamptodactyly, kidney hypoplasia, bilateral cryptorchidism, midshaft hypospadias, imperforate anus/anorectal agenesis, body asymmetry, mild developmental delay, hemimegalencephaly and facial dysmorphism (hypotelorism, downslanting palpebral fissures, low-set and posteriorly angulated ears, depressed nasal bridge, and microstomia).

274
(73.6%)

Maternal phenylketonuria

Brachydactyly Epicanthus Long philtrum Micrognathia

A rare disorder of phenylalanine metabolism, an inborn error of amino acid metabolism, characterized by the development of microcephaly, growth retardation, congenital heart disease, facial dysmorphism and intellectual disability in nonphenylketonuric offspring of mothers with excess phenylalanine (Phe) concentrations.

274
(73.6%)

Carey-Fineman-Ziter syndrome

Brachydactyly Epicanthus Long philtrum Micrognathia

Autosomal recessive inheritance

Carey-Fineman-Ziter (CFZ) syndrome is a rare condition characterized by the association of hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre-Robin sequence (micrognathia, glossoptosis, and high-arched or cleft palate), unusual face, and growth delay.

274
(73.6%)

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Brachydactyly Epicanthus Microretrognathia Thin upper lip vermilion

Autosomal dominant inheritance

274
(73.6%)

Trisomy 20p

Brachydactyly Epicanthus Micrognathia Smooth philtrum

Trisomy 20p is a chromosomal disorder resulting from duplication of all or part of the short arm of chromosome 20. It is mostly characterized by normal growth, mild to moderate intellectual disability, speech delay, poor coordination and evocative facial features.

279
(73.6%)

Rhizomelic syndrome, Urbach type

Abnormality of the tongue Cleft palate Micrognathia Rhizomelia Short distal phalanx of finger

Autosomal recessive inheritance

Rhizomelic syndrome, Urbach type is a rare primary bone dysplasia characterized by upper limbs rhizomelia and other skeletal anomalies (e.g. short stature, dislocated hips, digitalization of the thumb with bifid distal phalanx), craniofacial features (e.g. microcephaly, large anterior fontanelle, fine and sparse scalp hair, depressed nasal bridge, high arched palate, micrognathia, short neck), congenital heart defects (e.g. pulmonary stenosis), delayed psychomotor development and mild flexion contractures of elbows. Radiologic evaluation may reveal flared epiphyses, platyspondyly and/or digital anomalies.

279
(73.6%)

Diastrophic dwarfism

Cleft palate Micrognathia Micromelia Short finger

Autosomal recessive inheritance

A rare disorder marked by short stature with short extremities (final adult height is 120cm +/- 10cm), and joint malformations leading to multiple joint contractures (principally involving the shoulders, elbows, interphalangeal joints and hips).

281
(73.6%)

Brachymorphism-onychodysplasia-dysphalangism syndrome

Brachydactyly Epicanthus Long philtrum Short distal phalanx of toe

Autosomal dominant inheritance

Brachymorphism-onychodysplasia-dysphalangism (BOD) is a very rare malformation syndrome that is characterized by short stature, hypoplastic fifth digits with tiny dysplastic nails, facial dysmorphism with coarse features including a wide mouth and broad nose, and mild intellectual disability. It has been suggested that Coffin-Siris syndrome (see this term) and BOD syndrome are perhaps allelic variants.

281
(73.6%)

Roifman syndrome

Brachydactyly Long palpebral fissure Short toe Thin upper lip vermilion

Autosomal recessive inheritance X-linked recessive inheritance

Roifman syndrome is a rare, genetic immuno-osseous dysplasia disorder characterized by pre- and post-natal growth retardation, hypotonia, borderline to moderate intellectual disability, retinal dystrophy, spondyloepiphyseal dysplasia (epiphyseal dysplasia, epiphyses ossification delay, vertebral changes) and skeletal anomalies (brachydactyly, fifth finger clinodactyly), as well as humeral immunodeficiency characterized by inability to generate specific antibodies and low circulating B-cells. Craniofacial dysmorphism, that typically inlcudes microcephaly, hypertelorism, long palpebral fissures, prominent eyelashes, a narrow, tubular, upturned nose with hypoplastic alae nasi, long philtrum and thin upper lip, are also associated.

283
(73.6%)

Hall-Riggs syndrome

Brachydactyly Epicanthus Limb undergrowth Thick vermilion border

Autosomal recessive inheritance

Hall-Riggs syndrome is a very rare syndrome consisting of microcephaly with facial dysmorphism, spondylometaepiphyseal dysplasia and severe intellectual deficit.

284
(73.6%)

Radio-renal syndrome

Convex nasal ridge High, narrow palate Hypoplasia of the radius Micrognathia Short palm

Autosomal dominant inheritance

Radio-renal syndrome is a rare developmental defect during embryogenesis characterized by variable upper limb reduction defects and renal anomalies. Patients typically present absence/hypoplasia of digits, radii and/or ulnae, short stature and mild external ear malformation, as well as kidney agenesis or ectopia. There have been no further descriptions in the literature since 1983.

285
(73.5%)

Pelvis-shoulder dysplasia

Aplasia/hypoplasia of the femur Cleft palate Dislocated radial head Micrognathia Short palpebral fissure

Autosomal dominant inheritance

Pelvis-shoulder dysplasia is a rare focal skeletal dysostosis characterized by symmetrical hypoplasia of the scapulae and the iliac wings of the pelvis.

286
(73.5%)

Multiple pterygium-malignant hyperthermia syndrome

Abnormality of the mandible Arachnodactyly Downslanted palpebral fissures Hemiatrophy Long philtrum

Autosomal recessive inheritance

Malignant hyperthermia-arthrogryposis-torticollisis an extremely rare arthrogryposis syndrome, described in only two pairs of siblings from two unrelated families to date, and characterized by the association of arthrogryposis, congenital torticollis, dysmorphic facial features (i.e. asymmetry of the face, myopathic facial movements, ptosis, posteriorly rotated ears, cleft palate), progressive scoliosis and episodes of malignant hyperthermia. There have been no further descriptions in the literature since 1988.

287
(73.4%)

Camptodactyly syndrome, Guadalajara type 1

Epicanthus Mandibular prognathia Narrow mouth Short distal phalanx of finger

Autosomal recessive inheritance

Camptodactyly syndrome, Guadalajara type 1 is a rare syndrome consisting of growth retardation, facial dysmorphism, camptodactyly and skeletal anomalies.

288
(73.4%)

Fibrochondrogenesis

Brachydactyly Cleft palate Downslanted palpebral fissures Micromelia Short ribs

Fibrochondrogenesis is a rare, neonatally lethal, rhizomelic chondrodysplasia. Eleven cases have been reported. The face is distinctive and characterized by protuberant eyes, flat midface, flat small nose with anteverted nares and a small mouth with long upper lip. Cleft palate, micrognathia and bifid tongue can occur. The limbs show marked shortness of all segments with relatively normal hands and feet. No internal anomalies other than omphalocele have been reported. Transmission is probably autosomal recessive. Recurrence in a consanguineous family (affecting both sexes) and concordance of affected male twins have been reported.

289
(73.4%)

Ventricular extrasystoles with syncopal episodes-perodactyly-Robin sequence syndrome

Abnormality of the mandible Glossoptosis Short 4th metacarpal Short distal phalanx of finger Submucous cleft hard palate

Autosomal dominant inheritance

This syndrome is characterized by cardiac arrhythmias (ventricular extrasystoles manifesting as bigeminy or multifocal tachycardia with syncopal episodes), perodactyly (hypoplasia and/or agenesis of the distal phalanges of the toes) and Pierre-Robin sequence (see this term).

290
(73.4%)

Ring chromosome 6 syndrome

Epicanthus Micrognathia Short distal phalanx of finger

Ring chromosome 6 syndrome is a rare chromosomal anomaly syndrome with highly variable phenotype principally characterized by prenatal/postnatal growth failure, intellectual disability, developmental delay, craniofacial dysmorphism (incl. microcephaly, microphthalmia, epicanthus, low-set and malformed ears, broad and flat nasal bridge, full lips, micrognathia), central nervous system anomalies (e.g. hydrocephalus, cortical atrophy, ventriculomegaly), short neck, and delayed bone age. Cardiac defects, limb anomalies, hip joint malformations, and seizures have also been reported.

290
(73.4%)

Congenital ptosis

Micrognathia Short finger Telecanthus

Autosomal dominant inheritance

Congenital ptosis is characterized by superior eyelid drop present at birth.

292
(73.4%)

Craniofaciofrontodigital syndrome

Brachydactyly Diaphyseal dysplasia Epicanthus Hypoplastic vertebral bodies Long philtrum

Autosomal dominant inheritance Sporadic

Craniofaciofrontodigital syndrome is a rare multiple congenital anomalies syndrome characterized by mild intellectual disability, short stature, cardiac anomalies, mild dysmorphic features (macrocephaly, prominent forehead, hypertelorism, exophthalmos), cutis laxa, joint hyperlaxity, wrinkled palms and soles and skeletal anomalies (sella turcica, wide ribs and small vertebral bodies).

293
(73.4%)

Cleft palate-large ears-small head syndrome

Cleft palate Micrognathia Short distal phalanx of finger

Autosomal dominant inheritance

Cleft palate-large ears-small head syndrome is a rare, genetic syndrome characterized by cleft palate, large protruding ears, microcephaly and short stature (prenatal onset). Other skeletal abnormalities (delayed bone age, distally tapering fingers, hypoplastic distal phalanges, proximally placed thumbs, fifth finger clinodactyly), Pierre Robin sequence, cystic renal dysplasia, proximal renal tubular acidosis, hypospadias, cerebral anomalies on imaging (enlargement of lateral ventricles, mild cortical atrophy), seizures, hypotonia and developmental delay are also observed.

293
(73.4%)

Crane-Heise syndrome

Cleft palate Micrognathia Short distal phalanx of finger

Autosomal recessive inheritance

Crane-Heise syndrome is a very rare syndrome characterized by poorly mineralized calvarium, facial dysmorphism, vertebral abnormalities and absent clavicles.

295
(73.3%)

Growth delay-hydrocephaly-lung hypoplasia syndrome

Lower limb undergrowth Micrognathia Radial bowing Upslanted palpebral fissure

Autosomal recessive inheritance

Growth delay - hydrocephaly - lung hypoplasia, also named Game-Friedman-Paradice syndrome, is a rare developmental disorder described in 4 sibs so far and characterized by delayed fetal growth, hydrocephaly with patent aqueduct of Sylvius, underdeveloped lungs and various other anomalies such as small jaw, intestinal malrotation, omphalocele, shortness of lower limbs, bowed tibias and foot deformities.

296
(73.2%)

Robin sequence-oligodactyly syndrome

Abnormality of the ulna Cleft palate Glossoptosis Hand oligodactyly Micrognathia

Autosomal dominant inheritance

Robin sequence-oligodactyly syndrome is a rare, genetic, developmental defect during embryogenesis syndrome characterized by Robin sequence (i.e. severe micrognathia, retroglossia and U-shaped cleft of the posterior palate) associated with pre- and postaxial oligodactyly. Facial features can include a narrow face and narrow lower dental arch. Clinodactyly, absent phalanx, metacarpal fusions, and hypoplastic carpals have also been reported. There have been no further descriptions in the literature since 1986.

296
(73.2%)

Distal limb deficiencies-micrognathia syndrome

Abnormality of the ulna Aplasia/Hypoplasia of the thumb Cleft palate Microretrognathia Narrow mouth

Autosomal dominant inheritance Autosomal recessive inheritance

The distal limb deficiencies-micrognathia syndrome is characterized by the combination of symmetric severe distal limb reduction deficiencies affecting all four limbs (oligodactyly), microretrognathia, and microstomia with or without cleft palate.

298
(73.2%)

Incontinentia pigmenti

Abnormal hand morphology Absent hand Hemiatrophy Nasolacrimal duct obstruction Oral cleft

X-linked dominant inheritance

Incontinentia pigmenti (IP) is a rare X-linked dominant multi-systemic ectodermal dysplasia usually lethal in males and presenting neonatally in females with a bullous rash along Blashko's lines (BL) followed by verrucous plaques evolving over time to hyperpigmented swirling patterns. It is further characterized by teeth abnormalities, alopecia, nail dystrophy and affects occasionally the retina and the central nervous system (CNS).

299
(73.2%)

Cardiofaciocutaneous syndrome

Abnormality of the ulna Deep palmar crease Epicanthus Hypoplasia of the zygomatic bone Long philtrum

Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by craniofacial dysmorphology, congenital heart disease, dermatological abnormalities (most commonly hyperkeratotic skin and sparse, curly hair), growth retardation and intellectual disability.

300
(73.2%)

Truncus arteriosus

Bilateral cleft lip Postaxial oligodactyly Retrognathia Rhizomelia

Truncus arteriosus (TA) is a rare congenital cardiovascular anomaly characterized by a single arterial trunk arising from the heart by means of a single semilunar valve (i.e. truncal valve). Pulmonary arteries originate from the common arterial trunk distal to the coronary arteries and proximal to the first brachiocephalic branch of the aortic arch. TA typically overrides a large outlet ventricular septal defect (VSD). The intracardiac anatomy usually displays situs solitus and atrioventricular (AV) concordance.