1
(95.9%)

Postaxial acrofacial dysostosis

Eyelid coloboma Hypoplasia of the radius Hypoplasia of the ulna Micrognathia Non-midline cleft lip

Autosomal recessive inheritance

Postaxial acrofacial dysostosis (POADS) is a type of acrofacial dysostosis (see this term) characterised by mandibular and malar hypoplasia, small and cup-shaped ears, lower lid ectropion, and symmetrical postaxial limb deficiencies with absence of the fifth digital ray and ulnar hypoplasia.

2
(94.2%)

Nager syndrome

Aplasia/Hypoplasia of the thumb Eyelid coloboma Hypoplasia of the radius Microretrognathia Non-midline cleft lip

Autosomal dominant inheritance

A congenital malformation syndrome characterized by mandibulofacial dystosis (malar hypoplasia, micrognathia, external ear malformations) and variable preaxial limb defects.

3
(90.5%)

Alagille syndrome

Downslanted palpebral fissures Hypoplasia of the ulna Micrognathia Short distal phalanx of finger Short philtrum

A rare syndrome variably characterized by chronic cholestasis due to paucity of intrahepatic bile ducts, peripheral pulmonary artery stenosis, vertebrae segmentation anomalies, characteristic facies, posterior embryotoxon/anterior segment abnormalities, pigmentary retinopathy, and dysplastic kidneys.

4
(89.8%)

Syndactyly-telecanthus-anogenital and renal malformations syndrome

Eyelid coloboma Hypoplasia of the radius Thin upper lip vermilion

X-linked dominant inheritance

This syndrome is characterised by the association of toe syndactyly, facial dysmorphism including telecanthus (abnormal distance between the eyes) and a broad nasal tip, urogenital malformations and anal atresia.

5
(89.5%)

Acrofrontofacionasal dysostosis

Broad thumb Eyelid coloboma Micromelia Non-midline cleft lip Short distal phalanx of finger

Autosomal recessive inheritance

A rare congenital malformation syndrome characterized by the association of facial and skeletal anomalies with severe intellectual deficit and occasional genitourinary anomalies.

6
(88.3%)

Cenani-Lenz syndrome

Downslanted palpebral fissures Foot oligodactyly Hypoplasia of the ulna Short philtrum Short thumb

Autosomal recessive inheritance

Cenani-Lenz syndrome (CLS) is a congenital malformation syndrome that associates a complex syndactyly of the hands with malformations of the forearm bones and similar manifestations in the lower limbs.

7
(87.9%)

Distal trisomy 5q

Absent thumb Downslanted palpebral fissures Hypoplasia of the ulna Long philtrum Micrognathia

Distal trisomy 5q is a rare chromosomal anomaly syndrome, resulting from a partial duplication of the long arm of chromosome 5, characterized by short stature, moderate intellectual disability, and craniofacial dysmorphism (microcephaly, flat facies, large, low-set dysplastic ears, down-slanted, almond-shaped palpebral fissures, hypertelorism, epicanthal folds, small nose, long philtrum, small mouth with thin upper lip, and micrognathia). Patients also frequently present speech and cognitive delay, cardiac (ventriculomegaly, ventricular septum defect) and skeletal abnormalities (craniosynostosis, radial agenesis, ulnar hypoplasia, brachydactyly) and genital malformations (hypospadias, cryptorchidism).

8
(87.8%)

Cleft lip/palate

Cryptophthalmos Micrognathia Overlapping fingers Short long bone Unilateral cleft lip

Cleft lip and palate is a fissure type embryopathy extending across the upper lip, nasal base, alveolar ridge and the hard and soft palate.

9
(87.6%)

Bartsocas-Papas syndrome

Absent thumb Eyelid coloboma Median cleft lip Micrognathia

Autosomal recessive inheritance

Bartsocas-Papas syndrome is a rare, inherited, popliteal pterygium syndrome (see this term) characterized by severe popliteal webbing, microcephaly, a typical face with short palpebral fissures, ankyloblepharon, hypoplastic nose, filiform bands between the jaws and facial clefts, oligosyndactyly, genital abnormalities, and additional ectodermal anomalies (i.e. absent hair, eyebrows, lashes, nails). It is often fatal in the neonatal period, but patients living until childhood have been reported.

9
(87.6%)

Goldenhar syndrome

Aplasia/Hypoplasia of the thumb Micrognathia Non-midline cleft lip Upper eyelid coloboma

Autosomal dominant inheritance

Goldenhar syndrome (GS), also known as oculo-auriculo-vertebral dysplasia (OAV), is a rare developmental syndrome characterized by a classic triad of mandibular hypoplasia resulting in facial asymmetry, ear and/or eye malformations, and vertebral anomalies.

9
(87.6%)

Choanal atresia

Absent thumb Bilateral cleft lip Lower eyelid coloboma Micrognathia

Choanal atresia (CA) is a congenital anomaly of the posterior nasal airway characterized by the obstruction of one (unilateral) or both (bilateral) choanal aperture(s), with clinical manifestations ranging from acute respiratory distress to chronic nasal obstruction.

12
(87.3%)

Orofaciodigital syndrome type 10

Hypoplasia of proximal radius Long philtrum Micrognathia Short 4th finger Telecanthus

Autosomal dominant inheritance

Oral-facial-digital syndrome, type 10 is characterized by facial (telecanthus, flat nasal bridge, retrognathia), oral (cleft palate, vestibular frenula) and digital (oligodactyly, preaxial polydactyly) features, associated with remarkable radial shortening, fibular agenesis and coalescence of tarsal bones. The syndrome has been described in one 10-month-old girl. No new cases have been described since 1993.

13
(86.8%)

Microtia

Bilateral cleft lip Lower eyelid coloboma Microretrognathia Small hand

A congenital malformation of the external ear, seen more frequently in males, that occurs sporadically or is inherited, that is characterized by unilateral (79-93% of cases, 60% of which involve the right ear) or bilateral small and abnormally shaped auricles and that is often associated with atresia or stenosis of the ear canal, attention deficit disorders and delayed language development. The variation in auricle size ranges from grade I, where the auricle is simply smaller than normal, to grade IV, also known as anotia, where there is a complete absence of the external ear and of the auditory canal.

14
(86.8%)

Renal agenesis

Cryptophthalmos Large hands Median cleft lip Microretrognathia Short 4th metacarpal

Renal agenesis (RA) is a form of renal tract malformation characterized by the complete absence of development of one or both kidneys (unilateral RA or bilateral RA respectively; see these terms), accompanied by absent ureter(s).

15
(86.4%)

Acro-renal-mandibular syndrome

Downslanted palpebral fissures Hypoplasia of the radius Hypoplasia of the ulna Micrognathia Short philtrum

Autosomal recessive inheritance

A very rare multiple congenital anomalies syndrome characterized by limb deficiencies and renal anomalies that include split hand-split foot malformation, renal agenesis, polycystic kidneys, uterine anomalies and severe mandibular hypoplasia. An autosomal recessive mode of inheritance has been suggested.

16
(86.1%)

Oculocerebrocutaneous syndrome

Eyelid coloboma Missing ribs Oral cleft Short distal phalanx of finger

Sporadic

Oculocerebrocutaneous syndrome (OCCS) is a rare congenital disorder associated with an intellectual disability and is typically characterized by the triad of eye, central nervous system and skin malformations.

17
(85.1%)

Fanconi anemia

Aplasia/Hypoplasia of fingers Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia

Fanconi anemia (FA) is a hereditary DNA repair disorder characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors.

18
(85.0%)

MOMO syndrome

Eyelid coloboma Femoral bowing Large hands Short sternum Thick upper lip vermilion

Autosomal dominant inheritance Autosomal recessive inheritance

MOMO syndrome is a very rare genetic overgrowth/obesity syndrome (see this term) characterized by macrocephaly, obesity, mental (intellectual) disability and ocular abnormalities. Other frequent clinical signs include macrosomia, downslanting palpebral fissures, hypertelorism, broad nasal root, high and broad forehead and delay in bone maturation, in association with normal thyroid function and karyotype.

19
(84.9%)

Kabuki syndrome

Ablepharon Lower lip pit Micrognathia Short middle phalanx of finger

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by typical facial features, skeletal anomalies, mild to moderate intellectual disability and postnatal growth deficiency.

20
(84.4%)

Jacobsen syndrome

Eyelid coloboma Micrognathia Short toe Smooth philtrum

Sporadic

A multiple congenital anomaly/mental retardation (MCA/MR) contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11.

21
(84.2%)

W syndrome

Downslanted palpebral fissures Hypoplasia of the ulna Upper lip pit

X-linked inheritance

W syndrome is characterised by intellectual deficit, epileptic seizures and facial dysmorphism. Skeletal anomalies are also often present. To date, it has been described in six male patients. The mode of transmission appears to be X-linked dominant.

22
(84.2%)

Omphalocele

Absent radius Cryptophthalmos Long philtrum Micrognathia Short femur

Omphalocele is an embryopathy classified in the group of abdominal celosomias and is characterized by a large hernia of the abdominal wall, centered on the umbilical cord, in which the protruding viscera are protected by a sac.

23
(84.2%)

Brachydactyly type A1

Brachydactyly Hypoplasia of the ulna Short foot Short middle phalanx of finger

Brachydactyly type A1 (BDA1) is a congenital malformation characterized by apparent shortness (or absence) of the middle phalanges of all digits, and occasional fusion with the terminal phalanges.

24
(83.9%)

Wolf-Hirschhorn syndrome

Cleft upper lip Epicanthus Micrognathia Short long bone Short thumb

Autosomal dominant inheritance Sporadic

A developmental disorder characterized by typical craniofacial features, prenatal and postnatal growth impairment, intellectual disability, severe delayed psychomotor development, seizures, and hypotonia.

25
(83.9%)

Branchioskeletogenital syndrome

Eyelid coloboma Mandibular prognathia Short philtrum Upper limb peromelia

Autosomal recessive inheritance

Branchioskeletogenital syndrome is a rare multiple congenital anomalies/dysmorphic syndrome characterized by moderate intellectual disability, distinctive craniofacial features (including brachycephaly, facial asymmetry, marked hypertelorism, blepharochalasis, proptosis, a broad nose with concave nasal ridge and bulbous nasal tip, midface hypoplasia, bifid uvula or partial cleft palate, and prognathism), progressive dental anomalies (dentigerous cysts, radicular dentin dysplasia and early tooth loss), vertebral fusions (particularly of C2-C3), and hypospadias. Hearing loss is an additional observed feature.

26
(83.9%)

Atelosteogenesis type II

Epicanthus Micrognathia Short metacarpal Thin upper lip vermilion Upper limb undergrowth

Autosomal recessive inheritance

A rare, lethal perinatal bone dysplasia characterized by limb shortening, normal sized skull with cleft palate, hitchhiker thumbs, distinctive facial dysmorphism and radiographic skeletal features, caused by mutations in the diastrophic dysplasia sulfate transporter gene.

27
(83.7%)

Duane retraction syndrome

Aplasia/Hypoplasia of the thumb Epicanthus inversus Everted lower lip vermilion Hypoplasia of the radius Micrognathia

A congenital form of strabismus characterized by horizontal eye movement limitation, globe retraction and palpebral fissure narrowing in attempted adduction. It is caused by a failure of development of the abducens nerve and can lead to amblyopia.

28
(83.6%)

Holoprosencephaly-radial heart renal anomalies syndrome

Aplasia/Hypoplasia of the thumb Hypoplasia of the ulna Median cleft lip Missing ribs

Autosomal dominant inheritance

Holoprosencephaly-radial heart renal anomalies syndrome is characterised by holoprosencephaly, predominantly radial limb deficiency (absent thumbs, phocomelia), heart defects, kidney malformations and absence of gallbladder.

29
(83.2%)

Mycophenolate mofetil embryopathy

Eyelid coloboma Micrognathia Oral cleft Short palm

Mycophenolate mofetil (MMF) embryopathy is a malformative syndrome due to the teratogenic effect of MMF, an effective immunosuppressive agent widely used for the prevention of organ rejection after organ transplantation.

30
(83.2%)

Cornelia de Lange syndrome

Blepharitis Long philtrum Micrognathia Radioulnar synostosis Short 1st metacarpal

Cornelia de Lange syndrome (CdLS) is a multisystem disorder with variable expression marked by a characteristic facial dysmorphism, variable degrees of intellectual deficit, severe growth retardation beginning before birth (2nd trimester), abnormal hands and feet (oligodactyly, or sometimes an even more severe amputation, and constant brachymetacarpia of the first metacarpus), and various other malformations (heart, kidney etc.).

31
(83.2%)

17q24.2 microdeletion syndrome

Downslanted palpebral fissures Micrognathia Thin upper lip vermilion Upper limb undergrowth

32
(83.1%)

Trichorhinophalangeal syndrome type 1 and 3

Long philtrum Micrognathia Short distal phalanx of finger Short metatarsal Sparse eyelashes

Trichorhinophalangeal syndromes (TRPS) type 1 and 3 are malformation syndromes characterized by short stature, sparse hair, a bulbous nasal tip and cone-shaped epiphyses, as well as severe generalized shortening of all phalanges, metacarpals and metatarsal bones.

32
(83.1%)

8q24.3 microdeletion syndrome

Epicanthus Microretrognathia Short femur Short middle phalanx of the 5th finger Thin upper lip vermilion

32
(83.1%)

Interatrial communication

Epicanthus Micrognathia Short distal phalanx of the thumb Short long bone Smooth philtrum

Interauricular communication is a congenital malformation characterized by a communication between the atrial chambers of the heart.

35
(83.1%)

CHARGE syndrome

Brachydactyly Cleft upper lip Eyelid coloboma Micrognathia

Autosomal dominant inheritance Sporadic

CHARGE syndrome is a multiple congenital anomaly syndrome characterized by the variable combination of multiple anomalies, mainly Coloboma; Choanal atresia/stenosis; Cranial nerve dysfunction; Characteristic ear anomalies (known as the major 4 C's).

36
(83.0%)

Intellectual disability, Wolff type

Broad thumb Microretrognathia Non-midline cleft lip Short distal phalanx of finger Upslanted palpebral fissure

Intellectual disability, Wolff type is a rare intellectual disability syndrome characterized by severe intellectual disability, characteristic facial features (low anterior hairline, upward slanting palpebral fissures, ocular hypertelorism, broad, bulbous nose, large ears with helix incompletely developed, thick lips, and micrognathia) and additional anomalies including peripheral joint contractures, delayed skeletal maturation, bilateral cleft lip and palate, strabismus, terminal hypoplasia of fingers, hypospadias, and bilateral inguinal hernias.

37
(82.8%)

3M syndrome

Hypoplasia of the ulna Long philtrum Micromelia Thick eyebrow

Autosomal dominant inheritance

A primordial growth disorder characterized by low birth weight, reduced birth length, severe postnatal growth restriction, a spectrum of minor anomalies (including facial dysmorphism) and normal intelligence.

38
(82.6%)

Isolated split hand-split foot malformation

Bilateral cleft lip Fibular hypoplasia Microretrognathia Overlapping fingers Upslanted palpebral fissure

Split hand-split foot malformation (SHFM) refers to a spectrum of genetically and clinically heterogenous terminal limb defect (see this term) characterized by hypoplasia/ absence of central rays of the hands and feet (that can occur in one to all four digits), median clefts of the hands and/ or feet, aplasia and syndactyly, with a wide range of severity ranging from malformed central finger/ toe to a lobster claw-like appearance of the hands and feet. SHFM can be an isolated malformation or can be a feature in various syndromes (ADULT syndrome, EEC syndrome; see these terms). SHFM usually follows an autosomal dominant pattern of inheritance with incomplete penetrance, but autosomal recessive and rarely X-linked inheritance have also been reported.

39
(82.2%)

Acrocraniofacial dysostosis

Downslanted palpebral fissures Micrognathia Short 1st metacarpal Short distal phalanx of finger Short philtrum

Autosomal recessive inheritance

A very rare acrofacialdyosotosis characterized by short stature, acrocephaly, ocular hypertelorism, ptosis of eyelids, ocular proptosis, downslanting palpebral fissures, high nasal bridge, anteverted nostrils, short philtrum, cleft palate, micrognathia, abnormal external ears, preauricular pits, mixed hearing loss, bulbous digits, metatarsus varus, pectus excavatum and various radiological abnormalities. Features of this syndrome were reported to overlap with otopalatodigital syndrome types 1 and 2. There have been no further descriptions in the literature since 1988.

39
(82.2%)

Isolated oxycephaly

Blepharophimosis Broad thumb Micrognathia Short finger Smooth philtrum

Isolated oxycephaly is a late-appearing form of nonsyndromic craniosynostosis characterized by premature fusion of both the coronal and sagittal sutures, and, in some cases, of the lambdoid sutures. Compensatory growth in the region of the anterior fontanel results in a pointed or cone-shaped skull.