401
(71.6%)

Bannayan-Riley-Ruvalcaba syndrome

Broad thumb Long philtrum Micrognathia Narrow palate

Autosomal dominant inheritance

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis.

402
(71.6%)

Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome

Brachydactyly Cleft palate Glossoptosis Micrognathia Short femur

403
(71.5%)

Lymphedema-distichiasis syndrome

Cleft upper lip Ectropion Micrognathia

Autosomal dominant inheritance

Lymphedema - distichiasis is a rare syndromic lymphedema disorder characterized by lower-limb lymphedema and varying degrees of abnormal growth of eyelashes from the orifices of the Meibomian glands (distichiasis), with occasional associated manifestations.

403
(71.5%)

Emanuel syndrome

Micrognathia Submucous cleft lip Upslanted palpebral fissure

Emanuel syndrome is a constitutional genomic disorder due to the presence of a supernumerary derivative 22 chromosome and characterized by severe intellectual disability, characteristic facial dysmorphism (micrognathia, hooded eyelids, upslanting downslanting parebral fissures, deep set eyes, low hanging columnella and long philtrum), congenital heart defects and kidney abnormalities.

405
(71.4%)

Monosomy 5p

Epicanthus High palate Microretrognathia Small hand

Sporadic

Monosomy 5p, also known as Cri du chat syndrome, is a rare autosomal deletion syndrome characterized by a mewing cry (cri du chat) in infancy, multiple congenital anomalies, intellectual disability, microcephaly, and facial dysmorphism.

405
(71.4%)

Hallermann-Streiff syndrome

Abnormality of the tongue Micrognathia Small hand Telecanthus

Sporadic

Hallermann-Streiff syndrome is a rare genetic syndrome characterized mainly by head and facial abnormalities such as bird-like facies (with beak-shaped nose and retrognathia), hypoplastic mandible, brachycephaly with frontal bossing, dental abnormalities (e.g. absence of teeth, natal teeth, supernumerary teeth, severe agenesis of permanent teeth, enamel hypoplasia) hypotrichosis, various ophthalmic disorders (e.g. congenital cataracts, bilateral microphthalmia, ptosis, nystagmus) and atrophy of skin (especially around the center of face and nose) as well as telangiectasia and proportionate short stature. Intellectual disability is reported in some cases.

405
(71.4%)

Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation

Epicanthus High palate Micrognathia Small hand

Autosomal dominant inheritance

A rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disease characterized by the association of cortical dysplasia and pontocerebellar hypoplasia, manifesting with global developmental delay, mild to severe intellectual disability, axial hypotonia, strabismus, nystagmus and, occasionally, optic nerve hypoplasia. Brain imaging reveals variable malformations, including frontally predominant microgyria, gyral disorganization and simplification, dysmorphic and hypertrophic basal ganglia, cerebellar vermis dysplasia, brainstem/corpus callosum hypoplasia, and/or olfactory bulbs agenesis.

408
(71.4%)

Atelosteogenesis type III

Hand clenching High palate Micrognathia Short tubular bones of the hand

Autosomal dominant inheritance

A rare skeletal dysplasia characterized by short limbs dysmorphic facies and diagnostic radiographic findings.

409
(71.4%)

Velo-facial-skeletal syndrome

Abnormality of the dentition Epicanthus Large hands Short palm

Autosomal dominant inheritance

A very rare multiple congenital anomalies syndrome characterized by short stature, facial dysmorphism (elongated face, hypertelorism, broad and high nasal bridge, mild epicanthus, posteriorly angulated ears, narrow and high-arched palate), skeletal anomalies (mesomelic brachymelia, short broad hands, prominent finger pads, short stubby thumbs, hyperextensibility of small joints, small feet), hypernasality and normal intelligence. Delayed bone age has also been reported.

409
(71.4%)

Autosomal recessive spastic paraplegia type 20

Abnormal hand morphology Epicanthus Overbite Small hand

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 20 (SPG20) is a type of complex hereditary spastic paraplegia characterized by an onset in infancy of progressive spastic paraparesis associated with distal amyotrophy, psuedobulbar palsy, motor and cognitive delays, mild cerebellar signs (dysarthria, dysdiadochokinesia, mild intention tremor), short stature and subtle skeletal abnormalities (pes cavus, mild talipes equinovarus, kyphoscoliosis). SPG20 is due to mutations in the SPG20 gene (13q13.1), which encodes the protein spartin.

411
(71.4%)

Eiken syndrome

Absence of the sacrum Broad palm Fibular hypoplasia Short palm

Autosomal recessive inheritance

A rare, genetic, primary bone dysplasia syndrome characterized by multiple epiphyseal dysplasia, severely delayed ossification (mainly of the epiphyses, pubic symphysis, hands and feet), abnormal modeling of the bones in hands and feet, abnormal pelvis cartilage persistence, and mild growth retardation. Calcium, phosphate and vitamin D serum levels are typically within normal range, while parathyroid hormone serum levels are normal to slighly elevated. Oligodontia has been rarely associated.

412
(71.3%)

49,XYYYY syndrome

Coarse facial features Micrognathia Radioulnar synostosis Short 5th finger

49,XYYYY is a rare Y chromosome number anomaly with a variable phenotype mainly characterized by moderate to severe intellectual disability, speech delay, hypotonia, and mild dysmorphic features, including facial asymmetry, hypertelorism, bilateral low set 'lop' ears, and micrognatia. Skeletal abnormalities (such as skull deformities, radioulnar synostosis, elbow flexion, clinodactyly, brachydactyly) and behavourial problems have also been associated with this condition. Genitalia are normal at birth, although hypogonadism and azoospermia has been reported in adults.

413
(71.3%)

Recombinant 8 syndrome

Abnormality of the dentition Cleft upper lip Micrognathia Patellar aplasia

Autosomal dominant inheritance

Recombinant 8 (rec(8)) syndrome, also known as San Luis Valley syndrome, is a complex chromosomal disorder that is due to a parental pericentric inversion of chromosome 8 and is characterized by major congenital heart anomalies, urogenital malformations, moderate to severe intellectual deficiency and mild craniofacial dysmorphism.

414
(71.3%)

Imperforate oropharynx-costovertebral anomalies syndrome

Abnormality of the philtrum Arachnodactyly Epicanthus Missing ribs

Imperforate oropharynx-costovertebral anomalies syndrome is a dysostosis with predominant vertebral and costal involvement characterized by oropharyngeal atresia, mild mandibulofacial dysostosis, auricular malformations, and costovertebral anomalies (hemivertebrae, block vertebra, partial fusion of the ribs, absent ribs). There have been no further descriptions in the literature since 1989.

415
(71.2%)

Cryptomicrotia-brachydactyly-excess fingertip arch syndrome

Short distal phalanx of finger Telecanthus

Autosomal dominant inheritance

Cryptomicrotia - brachydactyly - excess fingertip arch syndrome describes a combination of malformations that include bilateral cryptomicrotia, brachytelomesophalangy with short middle and distal phalanges of digits 2 through 5, hypoplastic toenails and excess fingertip arch patterns, and has been reported in one family (mother and son). Cryptomicrotia - brachydactyly - excess fingertip arch syndrome is thought to follow an autosomal dominant transmission. There have been no further descriptions in the literature since 1988.

415
(71.2%)

Dahlberg-Borer-Newcomer syndrome

Short distal phalanx of finger Telecanthus Wide nasal bridge

Autosomal recessive inheritance X-linked recessive inheritance

Dahlberg-Borer-Newcomer syndrome is a very rare ectodermal dysplasia syndrome, described in 2 adult brothers, characterized by the association of hypoparathyroidism, nephropathy, congenital lymphedema, mitral valve prolapse and brachytelephalangy. Additional features include mild facial dysmorphism, hyperthricoses, and nail abnormalities.

417
(71.2%)

Branchiogenic deafness syndrome

Cleft palate Short distal phalanx of finger

Autosomal dominant inheritance

Branchiogenic deafness syndrome is a multiple congenital anomalies syndrome, described in one family to date, characterized by branchial cysts or fistulae; ear malformations; congenital hearing loss (conductive, sensorineural, and mixed); internal auditory canal hypoplasia; strabismus; trismus; abnormal fifth fingers; vitiliginous lesions, short stature; and mild learning disability. Renal and uretral abnormalities are absent.

417
(71.2%)

Early infantile epileptic encephalopathy

Cleft palate Short finger

A severe form of age-related epileptic encephalopathies characterized by the onset of tonic spasms within the first 3 months of life that can be generalized or lateralized, independent of the sleep cycle, and that can occur hundreds of times per day, leading to psychomotor impairment and death.

419
(71.2%)

Nasopalpebral lipoma-coloboma syndrome

Broad forehead Clinodactyly of the 5th finger Eyelid coloboma Hypoplasia of the maxilla

Autosomal dominant inheritance

Nasopalpebral lipoma-coloboma-telecanthus syndrome is characterized by nasopalpebral lipomas, bilateral lid coloboma, and telecanthus.

420
(71.2%)

Verloove Vanhorick-Brubakk syndrome

Cleft palate Limb undergrowth Micrognathia Non-midline cleft lip

Verloove Vanhorick-Brubakk syndrome is a multiple congenital anomalies/dysmorphic syndrome characterized by multiple skeletal malformations (short femora and humeri, bilateral absence of metatarsal and metacarpal bone in hands and feet, bilateral partial syndactyly of fingers and toes or oligopolysyndactyly, deformed lumbosacral spine), congenital heart disease (truncus arteriosus), lung and urogenital malformations (bilateral bilobar lungs, horseshoe kidney, cryptorchidism), and facial malformations (bilateral cleft lip and palate, micrognathia, small, low-set ears without external meatus). It is lethal in the neonatal period. There have been no further descriptions in the literature since 1981.

421
(71.1%)

Ulna hypoplasia-intellectual disability syndrome

Hypoplasia of the radius Hypoplasia of the ulna Large fontanelles Micromelia

Autosomal recessive inheritance

Ulna hypoplasia - intellectual deficit is a very rare syndrome characterized by mesomelic shortness of the forearms, bilateral clubfeet, aplasia or hypoplasia of all nails and severe psychomotor retardation.

422
(71.1%)

Pelviscapular dysplasia

Blepharophimosis Brachydactyly Hypoplastic scapulae Short femur

Autosomal recessive inheritance

Pelviscapular dysplasia (Cousin syndrome) is characterized by the association of pelviscapular dysplasia with epiphyseal abnormalities, congenital dwarfism and facial dysmorphism.

423
(71.0%)

Hutchinson-Gilford progeria syndrome

Absent eyelashes Metaphyseal widening Micrognathia Tapering pointed ends of distal finger phalanges Thin vermilion border

Autosomal dominant inheritance Autosomal recessive inheritance

Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant and premature aging disease, beginning in childhood and characterized by growth reduction, failure to thrive, a typical facial appearance (prominent forehead, protuberant eyes, thin nose with a beaked tip, thin lips, micrognathia and protruding ears) and distinct dermatologic features (generalized alopecia, aged-looking skin, sclerotic and dimpled skin over the abdomen and extremities, prominent cutaneous vasculature, dyspigmentation, nail hypoplasia and loss of subcutaneous fat).

424
(71.0%)

Marshall syndrome

Genu valgum Micrognathia Sparse eyelashes Thick upper lip vermilion

Autosomal dominant inheritance

A malformation syndrome that is characterized by facial dysmorphism, severe hypoplasia of the nasal bones and frontal sinuses, ocular involvement, early-onset hearing loss, skeletal and anhidrotic ectodermal anomalies and short stature with spondyloepiphyseal dysplasia and early-onset osteoarthritis.

424
(71.0%)

GAPO syndrome

Abnormality of the metaphysis Long philtrum Micrognathia Sparse eyelashes

Autosomal recessive inheritance

A multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations.

424
(71.0%)

Oculocerebrorenal syndrome of Lowe

Abnormality of the metaphysis Micrognathia Thin upper lip vermilion Upslanted palpebral fissure

X-linked recessive inheritance

Oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, glaucoma, intellectual disabilities, postnatal growth retardation and renal tubular dysfunction with chronic renal failure.

427
(71.0%)

McDonough syndrome

Bilateral single transverse palmar creases Micrognathia Short palpebral fissure Short philtrum

Autosomal recessive inheritance

McDonough syndrome is a rare, multiple congenital anomalies/dysmorphic syndrome characterized by facial dysmorphsim (prominent superciliary arcs, synophrys, strabismus, large, anteverted ears, large nose, malocclusion of teeth), delayed psychomotor development, intellectual disability and congenital heart defects (e.g. pulmonic stenosis, patent ductus arteriosus, atrial septal defect). Additional features include thorax deformation (pectus excavatum/carinatum), kyphoscoliosis, diastasis recti and cryptorchidism. There have been no further descriptions in the literature since 1984.

427
(71.0%)

Perlman syndrome

Abnormality of upper lip Bilateral single transverse palmar creases Epicanthus Micrognathia

Autosomal recessive inheritance

Perlman syndrome is characterized principally by polyhydramnios, neonatal macrosomia, bilateral renal tumours (hamartomas with or without nephroblastomatosis), hypertrophy of the islets of Langerhans and facial dysmorphism.

429
(71.0%)

Langerhans cell histiocytosis

Absent radius Oral ulcer Xanthelasma

Langerhans cell histiocytosis (LCH) is a systemic disease associated with the proliferation and accumulation (usually in granulomas) of Langerhans cells in various tissues.

430
(70.9%)

Rhizomelic dysplasia, Patterson-Lowry type

Epicanthus Mandibular prognathia Short humerus Short metacarpal

Autosomal recessive inheritance

Rhizomelic dysplasia, Patterson-Lowry type is a rare primary bone dysplasia characterized by short stature, severe rhizomelic shortening of the upper limbs associated with specific malformations of humeri (including marked widening and flattening of proximal metaphyses, medial flattening of the proximal epiphyses, and lateral bowing with medial cortical thickening of the proximal diaphyses), marked coxa vara with dysplastic femoral heads and brachimetacarpalia.

431
(70.9%)

Leprechaunism

Large hands Micrognathia Thick lower lip vermilion

Autosomal recessive inheritance

Leprechaunism is a congenital form of extreme insulin resistance (a group of syndromes that also includes Rabson-Mensenhall syndrome, type A insulin-resistance syndrome, and acquired type B insulin-resistance syndrome; see these terms) characterized by intrauterine and mainly postnatal severe growth retardation.

432
(70.9%)

Sotos syndrome

Downslanted palpebral fissures Genu valgum High palate Large hands Micrognathia

Sotos syndrome is a rare multisystemic genetic disorder characterized by a typical facial appearance, overgrowth of the body in early life with macrocephaly, and mild to severe intellectual disability.

433
(70.9%)

Stickler syndrome type 3

Abnormal metacarpal morphology Glossoptosis Long philtrum Micrognathia

Autosomal dominant inheritance

Stickler syndrome type 3 is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (midface hypoplasia, depressed nasal bridge, small nose with upturned tip, cleft palate, Pierre Robin sequence), bilateral, pronounced sensorineural hearing loss, and skeletal/joint anomalies (including spondyloepiphyseal dysplasia, arthralgia/arthropathy), in the absence of ocular abnormalities.

434
(70.9%)

Weissenbacher- Zweymuller syndrome

Cleft palate Glossoptosis Micrognathia Short femur

Weissenbacher-Zweymuller syndrome (WZS) is characterized by short stature at birth, neonatal micrognathia, cleft palate, rhizomelic chondrodysplasia with 'dumbbell' shaped arm and leg bones, hypertelorism and vertebral coronal clefts.

434
(70.9%)

Diabetic embryopathy

Cleft palate Micrognathia Short femur

A rare disorder characterized by congenital anomalies or foetal/neonatal complications in an infant that are linked to diabetes in the mother.

434
(70.9%)

Campomelic dysplasia

Cleft palate Fibular hypoplasia Micrognathia Short long bone

Autosomal dominant inheritance

Campomelic dysplasia is a very rare disorder characterised by a variable association of skeletal abnormalities (bowed and fragile long bones, pelvis and chest abnormalities, eleven rib pairs instead of the usual twelve), and extraskeletal abnormalities (facial dysmorphology, cleft palate, sexual ambiguity or sex reversal in two thirds of the affected boys, and brain, heart and kidney malformations).

437
(70.9%)

Spondyloepimetaphyseal dysplasia with joint laxity

Cleft palate Long philtrum Micromelia Short foot Short palm

438
(70.8%)

Acrocephalopolydactyly

Abnormality of the mouth Brachydactyly Epicanthus Limb undergrowth Short long bone

Autosomal recessive inheritance

An extremely rare lethal autosomal recessive disorder characterized by massive birth weight, swollen globular body, generalized edema, short limbs, postaxial polydactyly, thick skin, facial dysmorphism (slanted palpebral fissures, hypertelorism, epicanthic folds, dysplastic ears), excessive connective tissue, renal dysplasia, and in some patients, organomegaly, craniosynostosis with acrocephaly, omphalocele, cleft palate, and cryptorchidism. Fewer than 10 cases have been reported to date.

439
(70.8%)

Cleidorhizomelic syndrome

Abnormal clavicle morphology Rhizomelia Short middle phalanx of the 5th finger

Autosomal dominant inheritance

Cleidorhizomelic syndrome is a rhizo-mesomelic dysplasia characterized by rhizomelic short stature/dwarfism in combination with lateral clavicular defects. Additional manifestations include brachydactyly with bilateral clinodactyly and hypoplastic middle phalanx of the fifth digit. X-ray demonstrated an apparent Y-shaped or bifid distal clavicle. Cleidorhizomelic syndrome has been reported in one family (mother and son) and is suspected to be transmitted in an autosomal dominant manner. There have been no further descriptions in the literature since 1988.

440
(70.8%)

Feingold syndrome

Brachydactyly Micrognathia Oral cleft Short palpebral fissure

Feingold syndrome (FS), also known as oculo-digito-esophageal-duodenal (ODED) syndrome, is a rare inherited malformation syndrome characterized by microcephaly, short stature and numerous digital anomalies and is comprised of two subtypes: FS type 1 (FS1) and FS type 2 (FS2) (see these terms). FS1 is by far the most common form while FS2 has only been reported in 3 patients and has the same clinical characteristics as FS1, apart from the absence of gastrointestinal atresia and short palpebral fissures.

440
(70.8%)

3C syndrome

Brachydactyly Cleft palate Downslanted palpebral fissures Micrognathia

Cranio-cerebello-cardiac (3C) syndrome is a rare multiple congenital anomalies syndrome characterized by craniofacial (prominent occiput and forehead, hypertelorism, ocular coloboma, cleft palate), cerebellar (Dandy-Walker malformation, cerebellar vermis hypoplasia) and cardiac (tetralogy of Fallot, atrial and ventricular septal defects) anomalies (see these terms).

442
(70.8%)

Monosomy 13q14

Aplasia/Hypoplasia of the thumb Epicanthus Micrognathia

Autosomal dominant inheritance Sporadic

Monosomy 13q14 is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the long arm of chromosome 13, characterized by developmental delay, variable degrees of intellectual disability, retinoblastoma and craniofacial dysmorphism (incl. micro/dolichocephaly, high and broad forehead, prominent eyebrows, thick, anteverted ear lobes, short nose with a broad nasal bridge and bulbous tip, prominent philtrum, large mouth with thin upper lip and thick, everted lower lip). Other features reported include high birth weight, macrocephaly, pinealoma, hepatomegaly, inguinal hernia and cryptorchidism.

443
(70.8%)

Borjeson-Forssman-Lehmann syndrome

Blepharophimosis Oral cleft Short toe

X-linked recessive inheritance

Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked obesity syndrome characterized by intellectual deficit, truncal obesity, characteristic facial features, hypogonadism, tapered fingers and short toes.

444
(70.8%)

Arthrogryposis multiplex congenita-whistling face syndrome

Adducted thumb Blepharophimosis Micrognathia Thin vermilion border

Autosomal recessive inheritance

An extremely rare type of arthrogryposis multiplex congenita characterized by the combination of multiple joint contractures with movement limitation, microstomia with a whistling appearance of the mouth that may cause feeding, swallowing, and speech difficulties, a distinctive expressionless facies, severe developmental delay, central and autonomous nervous system dysfunction (excessive salivation, temperature instability, myoclonic epileptic fits, bradycardia), occasionally Pierre-Robin sequence, and lethality generally occurring during the first months of life. Arthrogryposis multiplex congenita-whistling face syndrome has been suggested to be a fetal akinesia deformation sequence.

444
(70.8%)

German syndrome

Camptodactyly of finger Downslanted palpebral fissures Everted lower lip vermilion Micrognathia

Autosomal recessive inheritance

German syndrome is an autosomal recessive arthrogryposis syndrome, described in 5 cases. Three of the four known families with affected children were Ashkenazi Jews. German syndrome is characterized by arthrogryposis, hypotonia-hypokinesia sequence, and lymphedema. Patients present distinct craniofacial appearance (tall forehead and ''carp''-shaped mouth, cleft palate), contractures, severe hypotonia manifesting as motor delay, and swallowing difficulties. The disease has a severe morbidity and mortality rate and survivors present a small stature, hypotonia, frequent upper respiratory infections, and psychomotor delay. There have been no further descriptions in the literature since 1987.

444
(70.8%)

Trisomy 18p

Abnormality of finger Micrognathia Telecanthus Thin vermilion border

Trisomy 18p is an extremely rare chromosomal anomaly with a poorly defined clinical phenotype. Reported manifestations include short stature, mild, moderate or severe developmental delay and intellectual disability, variable but mild facial dysmorphism, and epilepsy.

444
(70.8%)

LIG4 syndrome

Clinodactyly of the 5th finger Epicanthus Micrognathia Thin vermilion border

Autosomal recessive inheritance

LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).

444
(70.8%)

Intellectual disability-seizures-macrocephaly-obesity syndrome

Clinodactyly of the 5th finger Epicanthus Micrognathia Thick lower lip vermilion

Intellectual disability-seizures-macrocephaly-obesity syndrome is a rare syndromic obesity due to complex chromosomal rearrangement characterized by development delay and intellectual disability, childhood-onset obesity, seizures, poor coordination and broad-based gait, macrocephaly and mild dysmorphic features (such as narrow palpebral fissures, malar hypoplasia and thin upper lips), eczema, ocular abnormalities and a social personality.

444
(70.8%)

Axenfeld-Rieger syndrome

Arachnodactyly Epicanthus Everted lower lip vermilion Micrognathia

Axenfeld-Rieger syndrome (ARS) is a generic term used to designate overlapping genetic disorders, in which the major physical condition is anterior segment dysgenesis of the eye. Patients with ARS may also present with multiple variable congenital anomalies.

444
(70.8%)

Hennekam-Beemer syndrome

Clinodactyly of the 5th finger Micrognathia Thick lower lip vermilion Upslanted palpebral fissure

Autosomal recessive inheritance

Hennekam-Beemer syndrome is characterized by the association of skin mastocytosis (appearing as diffuse pigmentation), short stature, microcephaly, conductive hearing loss, and dysmorphic features. It has been described in only two (female) cases: one with normal mental development born to consanguineous parents and the other with severe psychomotor retardation born to unrelated parents. The mode of inheritance is most likely autosomal recessive.

451
(70.8%)

Frontorhiny

Brachydactyly Cleft palate Epicanthus Hypoplastic frontal sinuses

Autosomal recessive inheritance Sporadic

Frontorhiny is a distinct syndromic type of frontonasal malformation characterized by hypertelorism, wide nasal bridge, broad columella, widened philtrum, widely separated narrow nares, poor development of nasal tip, midline notch of the upper alveolus, columella base swellings and a low hairline. Additional features reported in some include upper eyelid ptosis and midline dermoid cysts of craniofacial structures and philtral pits or rugose folding behind the ears. An autosomal recessive inheritance has been proposed.

452
(70.8%)

Cleft palate-short stature-vertebral anomalies syndrome

Epicanthus Micrognathia Thin upper lip vermilion

Cleft palate- short stature- vertebral anomalies is a multiple congenital anomalies syndrome described in a father and son characterized by the association of cleft palate, peculiar facies (asymmetrical appearance, inner epicanthal folds, short nose, anteverted nostrils, low and back-oriented ears, thin upper lip and micrognathism), short stature, short neck , vertebral anomalies and intellectual disability. The transmission is presumed to be autosomal dominant. There have been no further descriptions in the literature since 1993.

452
(70.8%)

Distal monosomy 1q

Epicanthus Micrognathia Smooth philtrum

1qter deletion syndrome is a chromosomal anomaly characterized by an intellectual deficiency, progressive microcephaly, seizures, growth delay, distinct facial dysmorphic features and various midline defects including cardiac, corpus callosum, gastro-oesophalgeal and urogenital anomalies.

452
(70.8%)

Mitochondrial myopathy and sideroblastic anemia

Distichiasis Long philtrum Micrognathia

Mitochondrial myopathy and sideroblastic anemia belongs to the heterogeneous family of metabolic myopathies. It is characterised by progressive exercise intolerance manifesting in childhood, onset of sideroblastic anaemia around adolescence, lactic acidaemia, and mitochondrial myopathy.

452
(70.8%)

10q22.3q23.3 microduplication syndrome

Abnormality of the philtrum Microretrognathia Upslanted palpebral fissure

10q22.3q23.3 microduplication syndrome is a rare, chromosomal anomaly characterized by variable clinical features that may include developmental delay, mild intellectual disability and dysmorphic facial features. In some cases, microcephaly, growth retardation and congenital heart defects have been reported.

452
(70.8%)

14q11.2 microdeletion syndrome

Epicanthus Long philtrum Micrognathia

Sporadic

14q11.2 microdeletion syndrome is a recently described syndrome characterized by developmental delay, hypotonia and facial dysmorphism.

452
(70.8%)

Potocki-Shaffer syndrome

Epicanthus Micrognathia Short philtrum

Contiguous gene syndrome

Potocki-Shaffer syndrome is characterized by multiple exostoses, parietal foramina, enlargement of the anterior fontanelle and occasionally intellectual deficit and mild cranio-facial anomalies. To date, 23 individuals from 14 families have been reported. The syndrome is caused by contiguous gene deletions on the short arm of chromosome 11 (11p11.2).

452
(70.8%)

1q44 microdeletion syndrome

Epicanthus Micrognathia Smooth philtrum

1q44 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, developmental delay, in particular of expressive speech, seizures and hypotonia.

452
(70.8%)

Multiple benign circumferential skin creases on limbs

Epicanthus Long philtrum Micrognathia

452
(70.8%)

Pontocerebellar hypoplasia type 7

Epicanthus Micrognathia Thick upper lip vermilion

Autosomal recessive inheritance Sporadic

Pontocerebellar hypoplasia type 7 (PCH7) is a novel very rare form of pontocerebellar hypoplasia (see this term) with unknown etiology and poor prognosis reported in four patients and is characterized clinically during the neonatal period by hypotonia, no palpable gonads, micropenis and from infancy by progressive microcephaly, apneic episodes, poor feeding, seizures and regression of penis. MRI demonstrates a pontocerebellar hypoplasia. PCH7 is expressed as PCH with 46,XY disorder of sex development (see this term) in individuals with XY karyotype, and may be expressed as PCH only in individuals with XX karyotype.

452
(70.8%)

Ogden syndrome

Downslanted palpebral fissures Everted upper lip vermilion Microretrognathia

X-linked recessive inheritance X-linked dominant inheritance

Ogden syndrome is a rare, genetic progeroid syndrome characterized by a variable phenotype including postnatal growth delay, severe global developmental delay, hypotonia, non-specific dysmorphic facies with aged appearance and cryptorchidism, as well as cardiac arrthymias and skeletal anomalies. Patients typically present with widely opened fontanels, mainly truncal hypotonia, a waddling gait with hypertonia of the extremities, small hands and feet, broad great toes, scoliosis and redundant skin with lack of subcutaneous fat.

452
(70.8%)

22q11.2 microduplication syndrome

Epicanthus Micrognathia Smooth philtrum

Autosomal dominant inheritance Sporadic

The newly described 22q11.2 microduplication syndrome (dup22q11 syndrome) is the association of a broad clinical spectrum and a duplication of the region that is deleted in patients with DiGeorge or velocardiofacial syndrome (DG/VCFS; see this term), establishing a complementary duplication syndrome.

452
(70.8%)

Lateral meningocele syndrome

Epicanthus Micrognathia Smooth philtrum

Autosomal dominant inheritance

452
(70.8%)

6q terminal deletion syndrome

Broad philtrum Micrognathia Short palpebral fissure

6q terminal deletion syndrome is marked by a characteristic facial dysmorphism, short neck and psychomotor retardation, generally associated with a range of non-specific malformations.

452
(70.8%)

Endocardial fibroelastosis

Long philtrum Microretrognathia Telecanthus

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

Endomyocardial fibroelastosis is a cause of unexplained childhood cardiac insufficiency. It results from diffuse thickening of the endocardium leading to dilated myocardiopathy in the majority of cases and restrictive myocardiopathy in rare cases. It may occur as a primary disorder or may be secondary to another cardiac malformation, notably aortic stenosis or atresia.

466
(70.7%)

CODAS syndrome

Abnormality of dental enamel Epicanthus Short metacarpal

Autosomal recessive inheritance

Codas syndrome is a multiple congenital anomalies syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies.

467
(70.7%)

Heart-hand syndrome type 2

Abnormality of the dentition Abnormality of the ulna Micromelia Short distal phalanx of the thumb

Heart-hand syndrome type 2 is an extremely rare heart-hand syndrome (see this term) described in two families to date, that is characterized by upper limb malformations (brachytelephalangy type D, hypoplastic deltoids, mild shortening of the fourth and fifth metacarpals in some individuals, skeletal anomalies in the humerus, radius, ulnae, and thenar bones) and cardiac arrhythmias (junctional rhythms and atrial fibrillation).

468
(70.6%)

Growth delay due to insulin-like growth factor I resistance

Everted lower lip vermilion Short palm Smooth philtrum

Autosomal dominant inheritance Autosomal recessive inheritance

Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).

469
(70.6%)

Wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia

Dentinogenesis imperfecta Periorbital fullness Short foot Upper limb undergrowth

Autosomal dominant inheritance

Skeletal dysplasia with wormian bone-multiple fractures-dentinogenesis imperfecta is a skeletal disorder, reported in three patients to date, characterized clinically by multiple fractures, wormian bones of the skull, dentinogenesis imperfecta and facial dysmorphism (hypertelorism, periorbital fullness). Although the signs are very similar to osteogenesis imperfecta, characteristic cortical defects in the absence of osteopenia and collagen abnormalities are considered to be distinctive. There have been no further descriptions in the literature since 1999.

470
(70.5%)

Spondyloepimetaphyseal dysplasia, Shohat type

Micromelia Short femur Thin vermilion border

Autosomal recessive inheritance

Spondyloepimetaphyseal dysplasia congenita, Shohat type is characterized by severely disproportionate short stature, short limbs, small chest, short neck, thin lips, severe lumbar lordosis, marked genu varum, joint laxity, distended abdomen, mild hepatomegaly and splenomegaly.

471
(70.5%)

Fryns-Smeets-Thiry syndrome

Micrognathia Patellar aplasia Short philtrum Wide mouth

472
(70.5%)

Craniometadiaphyseal dysplasia, wormian bone type

Downslanted palpebral fissures High palate Micrognathia Short tubular bones of the hand

Autosomal dominant inheritance Autosomal recessive inheritance

Craniometadiaphyseal dysplasia, wormian bone type is an extremely rare craniotubular bone dysplasia syndrome described in fewer than 10 patients to date. Clinical manifestations include macrocephaly, frontal bossing, malar hypoplasia, prominent mandible and dental hypoplasia. Other skeletal anomalies include abnormal bone modeling in tubular bones, multiple wormian bones and deformities of chest, pelvis and elbows. An increased risk of fractures is noted.

473
(70.5%)

Seckel syndrome

Cleft lip Clinodactyly of the 5th finger Downslanted palpebral fissures Micrognathia Proximal femoral epiphysiolysis

Seckel syndrome is a type of microcephalic primordial dwarfism that is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly, a typical dysmorphic face (bird-like), and mild to severe intellectual disability.

474
(70.5%)

Guttmacher syndrome

Short thumb Small nail

Autosomal dominant inheritance

Guttmacher syndrome is an extremely rare syndrome characterized by hypoplastic thumbs and halluces, 5th finger clinobrachydactyly, postaxial polydactyly of the hands, short or uniphalangeal 2nd toes with absent nails and hypospadias.

474
(70.5%)

Familial digital arthropathy-brachydactyly

Brachydactyly Short middle phalanx of finger Shortening of all distal phalanges of the toes

Autosomal dominant inheritance

Familial digital arthropathy-brachydactyly is characterised by the association of arthropathy of interphalangeal, metacarpophalangeal and metatarsophalangeal joints with brachydactyly of the middle and distal phalanges. It has been described in numerous members from five generations of one large family. Inheritance is autosomal dominant.

474
(70.5%)

Hirschsprung disease-type D brachydactyly syndrome

Brachydactyly Short distal phalanx of the thumb

Hirschsprung disease-type D brachydactyly syndrome is characterized by Hirschsprung disease and absence or hypoplasia of the nails and distal phalanges of the thumbs and great toes (type D brachydactyly). It has been described in four males from one family (two brothers and two maternal uncles). Transmission appears to be X-linked recessive but autosomal dominant inheritance with incomplete penetrance in females can not be ruled out.

474
(70.5%)

Heart-hand syndrome type 3

Brachydactyly Short middle phalanx of finger Short toe

Autosomal dominant inheritance

Heart-hand syndrome type 3 is a very rare heart-hand syndrome (see this term), described in three members of a Spanish family to date, which is characterized by a cardiac conduction defect (sick sinus, bundle-branch block) and brachydactyly, resembling brachydactyly type C of the hands (see this term), affecting principally the middle phalanges in conjunction with an extra ossicle on the proximal phalanx of both index fingers. Feet abnormalities are more subtle.

474
(70.5%)

Brachydactyly type A4

Brachydactyly Short middle phalanx of the 5th finger

Autosomal dominant inheritance

Brachydactyly type A4 (BDA4) is a congenital malformation characterized by brachymesophalangy affecting mainly the 2nd and the 5th digit.

474
(70.5%)

Brachydactyly type B2

Short distal phalanx of finger Short foot

Autosomal dominant inheritance

A rare, genetic congenital limb malformation disorder characterized by hypoplasia/aplasia of distal and/or middle phalanges in fingers and toes II-V (frequently severe in fingers/toes IV-V, milder in fingers/toes II-III) in association with proximal, and occasionally distal, symphalangism, fusion of carpal/tarsal bones and partial cutaneous syndactyly. Additional reported features include proximal placement of thumbs, sensorineural hearing loss and farsightedness.

474
(70.5%)

X-linked skeletal dysplasia-intellectual disability syndrome

Diabetes insipidus Short middle phalanx of finger

X-linked inheritance X-linked recessive inheritance

Skeletal dysplasia-intellectual disability syndrome combines skeletal anomalies (short stature, ridging of the metopic suture, fusion of cervical vertebrae, thoracic hemivertebrae, scoliosis, sacral hypoplasia and short middle phalanges) and mild intellectual deficit. It has been described in four male cousins in three sibships. Glucose intolerance was present in three cases, and imperforated anus in one case. Carrier females had minor manifestations (fusion of cervical vertebrae and glucose intolerance). Transmission seems to be X-linked.

474
(70.5%)

Lung agenesis-heart defect-thumb anomalies syndrome

Abnormality of the ribs Short thumb

Autosomal recessive inheritance

Lung agenesis - heart defect - thumb anomalies is a very rare syndrome characterized by unilateral complete or partial lung agenesis, congenital cardiac defects and ipsilateral thumb anomalies.

474
(70.5%)

Weill-Marchesani syndrome

Glaucoma Short thumb

Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of the lens, severe myopia, and glaucoma.

483
(70.4%)

Fibular hemimelia

Abnormal morphology of ulna Craniosynostosis Short toe

Fibular hemimelia is a congenital longitudinal limb deficiency characterized by complete or partial absence of the fibula bone.

484
(70.4%)

Cloverleaf skull-multiple congenital anomalies syndrome

Micrognathia Proximal placement of thumb Rhizomelia Short philtrum

Autosomal recessive inheritance

This newly described syndrome is characterized by cloverleaf skull, limb anomalies, facial dysmorphism and multiple congenital anomalies.

485
(70.4%)

Intellectual disability, Birk-Barel type

Broad philtrum Congenital finger flexion contractures Highly arched eyebrow Micrognathia

Autosomal dominant inheritance

Intellectual disability, Birk-Barel type is a rare, genetic, syndromic intellectual disability characterized by congenital central hypotonia, developmental delay, moderate to severe intellectual disability and subtle dysmorphic features which evolve over time (dolichocephaly, myopathic facies, ptosis, short and broad philtrum, tented upper lip vermillion, palatal anomalies, mild micro- and/or retrognathia). Patients present reduced facial movements, lethargy, weak cry, transient neonatal hypoglycemia, severe feeding difficulties and failure to thrive. Dysphagia, particularly of solid food, asthenic body build, joint contractures and scoliosis are additional features.

485
(70.4%)

8p inverted duplication/deletion syndrome

Clinodactyly of the 5th finger Long philtrum Micrognathia Synophrys

8p inverted duplication/deletion [invdupdel(8p)] syndrome is a rare chromosomal anomaly characterized clinically by mild to severe intellectual deficit, severe developmental delay (psychomotor and speech development), hypotonia with tendency to develop progressive hypertonia and severe orthopedic problems over time, minor facial anomalies and agenesis of the corpus callosum.

487
(70.4%)

Schneckenbecken dysplasia

Cleft palate Fibular hypoplasia Short ribs

Autosomal recessive inheritance

Schneckenbecken dysplasia (or chondrodysplasia with snail-like pelvis) is a prenatally lethal spondylodysplastic dysplasia.

488
(70.3%)

Sirenomelia

Absence of the sacrum Absent external genitalia Aplasia/Hypoplasia of the radius

Sirenomelia is a rare, genetic, developmental defect during embryogenesis disorder characterized by fusion of the lower limbs and associated with some degree of lower extremity reduction and persistent vitelline artery. Patients also present severe malformations of the musculoskeletal system (e.g. sacral agenesis), as well as the urogenital and lower gastrointestinal tracts (e.g. renal agenesis, absent bladder, rectal/anal atresia, and absent internal genitalia). Most cases are stillborn, or die during, or shortly after, birth.

489
(70.3%)

Melnick-Needles syndrome

Delayed eruption of teeth Full cheeks Micrognathia Short distal phalanx of finger

X-linked dominant inheritance

Melnick-Needles syndrome (MNS) belongs to the otopalatodigital syndrome spectrum disorder and is associated with a short stature, facial dysmorphism, osseous abnormalities involving the majority of the axial and appendicular skeleton resulting in impaired speech and masticatory problems.

489
(70.3%)

Progeria-short stature-pigmented nevi syndrome

Bifid uvula Micrognathia Short distal phalanx of finger

Autosomal dominant inheritance Autosomal recessive inheritance

Progeria-short stature-pigmented nevi is a progeroid disorder characterised by low birthweight, short stature, multiple pigmented nevi and lack of facial subcutaneous fat.

491
(70.3%)

Desbuquois syndrome

Abnormal eyelash morphology Anteverted nares Radioulnar synostosis Short metacarpal

Desbuquois syndrome (DBQD) is an osteochondrodysplasia characterized by severe micromelic dwarfism, facial dysmorphism, joint laxity with multiple dislocations, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant (see these terms), has also been described and is characterized by short stature and articular, minor facial and significant hand anomalies.

492
(70.3%)

Pseudohypoparathyroidism type 1C

Conjunctivitis Delayed eruption of teeth Short 3rd metacarpal Short fifth metatarsal

Autosomal dominant inheritance

Pseudohypoparathyroidism type 1c (PHP1c) is a rare type of pseudohypoparathyroidism (PHP; see this term) characterized by resistance to parathyroid hormone (PTH) and other hormones, which manifests with hypocalcemia, hyperphosphatemia and elevated PTH levels, a constellation of clinical features collectively termed Albright's hereditary osteodystrophy (AHO; see this term), but normal activity of the stimulatory protein G (Gs alpha).

492
(70.3%)

Pseudohypoparathyroidism type 1A

Conjunctivitis Delayed eruption of teeth Short 3rd metacarpal Short fifth metatarsal

Autosomal dominant inheritance

Pseudohypoparathyroidism type 1A (PHP1a) is a type of pseudohypoparathyroidism (PHP; see this term) characterized by renal resistance to parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and elevated PTH; resistance to other hormones including thydroid stimulating hormone (TSH), gonadotropins and growth-hormone-releasing hormone (GHRH); and a constellation of clinical features known as Albright hereditary osteodystrophy (AHO; see this term).

494
(70.3%)

Symbrachydactyly of hands and feet

Abnormality of the ulna Aplasia/Hypoplasia of the radius Aplasia/Hypoplasia of the thumb Scoliosis

Symbrachydactyly of hands and feet is a rare, non-syndromic limb reduction defect disorder characterized by unilateral or bilateral brachydactyly, cutaneous syndactyly and global hypoplasia of the hand and/or foot, with underlying muscles, tendons, ligaments and bones being affected but without other associated limb anomalies. Patients typically present short, stiff, webbed or missing fingers and/or toes which are often replaced with small stumps (nubbins) with residual nails.

494
(70.3%)

Humero-radio-ulnar synostosis

Abnormality of the ureter Aplasia/Hypoplasia of the thumb Radioulnar synostosis

Humero-radio-ulnar synostosis is an extremely rare, genetic, congenital joint formation defect disorder characterized by uni- or bilateral fusion of the humerus, radius and ulnar bones, leading to loss of elbow motion and, in most, functional arm incapacity. It may appear as distal humeral bifurcation with absent elbow joint and shortened arm length on imaging. Hand abnormalities, namely oligoectrosyndactyly, may be associated.

496
(70.3%)

Postaxial polydactyly-dental and vertebral anomalies syndrome

Brachydactyly Cleft palate Epicanthus Hypoplastic vertebral bodies

Autosomal recessive inheritance

Postaxial polydactyly-dental and vertebral anomalies syndrome is a rare, genetic, developmental defect during embryogenesis syndrome characterized by postaxial polydactyly and other abnormalities of the hands and feet (e.g. brachydactyly, broad toes), hypoplasia and fusion of the vertebral bodies, as well as dental abnormalities (fused teeth, macrodontia, hypodontia, short roots). There have been no further descriptions in the literature since 1977.

497
(70.2%)

SCARF syndrome

Epicanthus Long philtrum Short sternum

X-linked recessive inheritance

SCARF syndrome is characterised by the association of skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, psychomotor retardation and facial abnormalities. So far, it has been described in two males (maternal first cousins). The mode of inheritance was suggested to be X-linked recessive.

498
(70.2%)

Eye defects-arachnodactyly-cardiopathy syndrome

Arachnodactyly Cleft palate Craniofacial hyperostosis Non-midline cleft lip Radioulnar synostosis

499
(70.2%)

Aase-Smith syndrome

Aplasia/Hypoplasia of the radius Cleft palate Trismus

Autosomal dominant inheritance

A very rare genetic disorder characterised by the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate, and severe joint contractures.

500
(70.2%)

Acromesomelic dysplasia, Grebe type

Aplasia/Hypoplasia of the thumb Brachydactyly Fibular hypoplasia Short foot

Autosomal recessive inheritance

A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism at birth, abnormalities confined to limbs, severe shortening and deformity of long bones, fusion or absence of carpal and tarsal bones, ball shaped fingers and, occasionally, polydactyly and absent joints. As seen in acromesomelic dysplasia, Hunter-Thomson type and acromesomelic dysplasia, Maroteaux Type, facial features and intelligence are normal.