501
(70.2%)

Radial hemimelia

Abnormal thumb morphology Aplasia of the 1st metacarpal Aplasia/Hypoplasia of the radius

Radial hemimelia is a congenital longitudinal deficiency of the radius bone of the forearm characterized by partial or total absence of the radius.

502
(70.1%)

Proboscis lateralis

Encephalocele Eyelid coloboma Median cleft lip

Proboscis lateralis (PL) is a rare congenital facial abnormality characterized by failed development of the external nose on one side that is replaced by a tubular structure composed of skin and soft tissue usually attached at the inner canthus of the eye and therefore often associated with maldevelopment of the nasal cavity or paranasal sinuses of the affected side. PL is also associated with other craniofacial abnormalities such as orbital anomalies, cleft lip/palate, frontal encephalocele and holoprosencephaly (see these terms).

502
(70.1%)

Frontofacionasal dysplasia

Brachycephaly Non-midline cleft lip Upper eyelid coloboma

Autosomal recessive inheritance

A rare congenital malformation characterized by multiple craniofacial anomalies (brachycephaly, blepharophimosis, ptosis, S-shaped palpebral fissures, coloboma, cleft lip and palate, deformed nostrils, encephalocele, hypertelorism, midface hypoplasia, malformed eyes, and absent inner eyelashes).

504
(70.1%)

VACTERL with hydrocephalus

Hypoplasia of the radius Micrognathia Retrognathia

Autosomal recessive inheritance X-linked recessive inheritance

VACTERL is an acronym for Vertebral anomalies, Anal atresia, Congenital cardiac disease, Tracheoesophageal fistula, Renal anomalies, and Limb defects. VACTERL associated with hydrocephalus has rarely been reported and is thought to be an autosomal recessive anomaly. The condition is described as a uniformly lethal or developmentally devastating disorder distinct from the VATER association.

505
(70.1%)

Gorlin syndrome

Arachnodactyly Brachydactyly Cleft lip Epicanthus Mandibular prognathia

Autosomal dominant inheritance Heterogeneous

A rare hereditary disorder due to autosomal dominant transmission with hamartosis characterized by multiple early-onset basal cell carcinoma (BCC), multiple jaw keratocysts and skeletal abnormalities.

506
(70.0%)

Pseudoachondroplasia

Hypoplasia of the odontoid process Platyspondyly Short metacarpal Short palm

Autosomal dominant inheritance

Pseudoachondroplasia is characterized by severe growth deficiency and deformations such as bow legs and hyperlordosis.

507
(70.0%)

Xp22.13p22.2 duplication syndrome

Downslanted palpebral fissures High palate Mandibular prognathia Small hand

Xp22.13p22.2 duplication syndrome is a rare syndromic intellectual disability characterized by developmental delay and intellectual disability, learning and behavioral problems, short stature, thin and sparse hair, mild dysmorphic features, tapering fingers and later onset of scoliosis, obesity and cardiovascular problems (cardiomegaly and cardiomyopathy). Females have normal intelligence.

507
(70.0%)

SHORT syndrome

Abnormality of the dentition Abnormality of the mandible Short palm Telecanthus

Autosomal dominant inheritance

A rare disorder characterized by multiple congenital anomalies. The name is a mneumonic for the common features observed in SHORT syndrome that include; short stature, hyperextensibility of joints, ocular depression, Rieger anomaly and teething delay. Other common manifestations of SHORT syndrome are mild intrauterine growth restriction, partial lipodystrophy, delayed bone age, hernias and a recognizable facial gestalt.

509
(70.0%)

Cleft velum

Blepharochalasis Flexion contracture of finger Micrognathia Thin vermilion border

Autosomal dominant inheritance Multifactorial inheritance

Cleft velum is a fissure type embryopathy that affects in varying degrees the soft palate.

510
(69.9%)

Radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome

Hypoplasia of the radius Mandibular prognathia

Autosomal dominant inheritance

Radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome is characterised by symmetric, nonopposable triphalangeal thumbs and radial hypoplasia. It has been described in eight patients (five females and three males) spanning generations of a family. The affected males also presented with hypospadias. The syndrome is inherited as an autosomal dominant trait.

511
(69.9%)

Cleidocranial dysplasia

Abnormality of the metacarpal bones Brachydactyly Cleft lip Glossoptosis Micrognathia

Autosomal dominant inheritance

Cleidocranial dysplasia (CCD) is a rare genetic developmental abnormality of bone characterized by hypoplastic or aplastic clavicles, persistence of wide-open fontanels and sutures and multiple dental abnormalities.

512
(69.9%)

3q27.3 microdeletion syndrome

Arachnodactyly Downslanted palpebral fissures Mandibular prognathia Thin upper lip vermilion

3q27.3 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 3, characterized by mild to severe intellectual disability, neuropsychiatric disorders of the psychotic and dysthymic spectrum, mild distinctive facial dysmorphism (incl. slender face, deep-set eyes, high nasal bridge with a hooked nose, small, low- set ears, short philtrum, small mouth with thin upper lip, prognathism) and a marfanoid habitus.

512
(69.9%)

Anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome

Abnormal size of the palpebral fissures Long philtrum Mandibular prognathia Ulnar deviation of finger

Anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome is a multiple congenital anomalies syndrome, reported in the offsprings of a consanguineous couple and characterized by multiple congenital skeletal (dolichocephaly, skull asymmetry, camptodactyly, clubfoot), muscular (muscle hypoplasia), ocular (anophthalmia, buphthalmos, retinal detachment, aniridia (see this term)) and cardiac (prolapse of tricuspid valves, mitral and tricuspid insufficiency) abnormalities. An autosomal recessive inheritance with variable expressivity was suspected. There have been no further descriptions in the literature since 1992.

512
(69.9%)

Renpenning syndrome

Abnormal thumb morphology Epicanthus Mandibular prognathia Short philtrum

X-linked recessive inheritance

Renpenning syndrome is an X-linked intellectual disability syndrome (XLMR, see this term) characterized by intellectual deficiency, microcephaly, leanness and mild short stature.

512
(69.9%)

Monosomy 22

Clinodactyly of the 5th finger Epicanthus Long philtrum Retrognathia Single transverse palmar crease

A rare autosomal anomaly syndrome, with a highly variable phenotype, typically characterized by short length, joint abnormalities (e.g. dysplasia, hyperextensibility, contractures, dislocation), congenital cardiac defects, and craniofacial dysmorphism (incl. microcephaly, a high, prominent, narrow and/or hairy forehead, epicanthus, upward-slanting and/or small palpebral fissures, broad, high or depressed nasal bridge and malformed ears). Delayed motor development and intellectual disability is observed in patients not presenting early demise.

512
(69.9%)

Hennekam syndrome

Camptodactyly of finger Epicanthus Retrognathia Short philtrum

Hennekam syndrome is characterised by the association of lymphoedema, intestinal lymphangiectasia, intellectual deficit and facial dysmorphism.

512
(69.9%)

X-linked intellectual disability, Snyder type

Arachnodactyly Mandibular prognathia Smooth philtrum Upslanted palpebral fissure

X-linked recessive inheritance

X-linked intellectual disability, Snyder type is a rare X-linked intellectual disability syndrome characterized by hypotonia, asthenic build with diminished muscle mass, severe generalized psychomotor delay, unsteady gait and moderate to severe intellectual disability, as well as a long, thin, asymmetrical face with prominent lower lip, long fingers and toes and nasal, dysarthric or absent speech. Bone abnormalities (e.g., osteoporosis, kyphoscoliosis, fractures, joint contractures) are also characteristic. Myoclonic, or myoclonic-like, seizures and renal abnormalities have been associated in some patients.

512
(69.9%)

2p15p16.1 microdeletion syndrome

Epicanthus Retrognathia Smooth philtrum Tapered finger

Sporadic

2p15p16.1 microdeletion syndrome is a recently described syndrome characterized by developmental delay and facial dysmorphism.

512
(69.9%)

Monosomy 18q

Abnormal palmar dermatoglyphics Arachnodactyly Epicanthus Mandibular prognathia Short philtrum

Autosomal dominant inheritance Sporadic

Monosomy 18q is a partial deletion of the long arm of chromosome 18 characterized by highly variable phenotype, most commonly including hypotonia, developmental delay, short stature, growth hormone deficiency, hearing loss and external ear anomalies, intellectual disability, palatal defects, dysmorphic facial features, skeletal anomalies (foot deformities, tapering fingers, scoliosis) and mood disorders.

512
(69.9%)

PMM2-CDG

Epicanthus Long fingers Retrognathia Thin upper lip vermilion

Autosomal recessive inheritance

PMM2-CDG is the most frequent form of congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults.

521
(69.9%)

Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16

Epicanthus High palate Micrognathia Short toe

Autosomal dominant inheritance Contiguous gene syndrome

A syndrome linked to chromosome 16 (ATR-16), a contiguous gene deletion syndrome, is a form of alpha-thalassemia characterized by microcytosis, hypochromia, normal hemoglobin (Hb) level or mild anemia, associated with developmental abnormalities.

522
(69.9%)

Atresia of small intestine

Adactyly Aglossia Cleft lip

Autosomal recessive inheritance Multifactorial inheritance

A special form of intestinal atresia with absence of mesentery, which is most likely due to an intrauterine intestinal vascular accident. Newborns are usually preterm infants with low birth-weights, that encounter feeding difficulties (including vomiting with initial feeds, which may later worsened and the abdomen becomes progressively distended) as well as failure to thrive. Affected children present disrupted bowel loops assuming a spiral configuration resembling an 'apple peel' and may have less than half of the normal length of the small bowel and a physiologically short bowel. This disorder is characterized by jejunal atresia near the ligament of Treitz, foreshortened bowel, and a large mesenteric gap. The bowel distal to the atresia is precariously supplied. It may be a manifestation of cystic fibrosis and the most important cause of mortality is short bowel syndrome, encountered in 65% of cases.

523
(69.8%)

Distal Xq28 microduplication syndrome

Clinodactyly Hypoplasia of the maxilla Thick lower lip vermilion Upper eyelid edema

Distal Xq28 microduplication syndrome is a rare, hereditary, syndromic intellectual disability characterized by cognitive impairment, behavioral and psychiatric problems, recurrent infections, atopic diseases, and distinctive facial features in males. Females are clinically asymptomatic or mildly affected, presenting mild learning difficulties and facial dysmorphism.

524
(69.8%)

Müllerian duct anomalies-limb anomalies syndrome

Aplasia/Hypoplasia of the ulna Microcephaly Micromelia Short humerus

Autosomal dominant inheritance

Mullerian duct anomalies-limb anomalies syndrome is characterised by the association of mullerian duct and distal limb anomalies. It has been described in five individuals from one family. Females presented with anomalies ranging from a vaginal septum to complete duplication of uterus and vagina, and males presented with micropenis. The limb anomalies varied from postaxial polydactyly to severe upper limb hypoplasia with split hand. The mode of transmission is autosomal dominant.

524
(69.8%)

Diaphragmatic defect-limb deficiency-skull defect syndrome

Aplasia/Hypoplasia of the fibula Aplasia/Hypoplasia of the ulna Decreased skull ossification

Autosomal recessive inheritance

Diaphragmatic defect-limb deficiency-skull defect syndrome is characterized by the association of classical diaphragmatic hernia (Bochdalek type) with severe lung hypoplasia, and variable associated malformations.

526
(69.8%)

Aplasia cutis congenita

Limbal dermoid Short finger

Autosomal dominant inheritance Autosomal recessive inheritance

A rare skin disorder characterized by localized absence of skin that is usually located on the scalp but can occur anywhere on the body including the face, trunk and extremities. ACC may occasionally be associated with other anomalies.

527
(69.8%)

8q22.1 microdeletion syndrome

Camptodactyly of finger Hypoplasia of the maxilla Long philtrum Telecanthus

Autosomal dominant inheritance Autosomal recessive inheritance Sporadic

The 8q22.1 microdeletion syndrome or Nablus mask-like facial syndrome is a rare microdeletion syndrome associated with a distinct facial appearance.

528
(69.8%)

Symptomatic form of Coffin-Lowry syndrome in female carriers

Downslanted palpebral fissures Everted lower lip vermilion Frontal bossing Large hands

528
(69.8%)

Ring chromosome 22 syndrome

Epicanthus Large hands Microcephaly Thick vermilion border

Ring chromosome 22 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including global developmental delay, hypotonia, growth retardation with microcephaly, intellectual disability with severe speech delay, seizures or abnormal EEG, autistic spectrum disorder and other behavioral characteristics.

530
(69.7%)

Cleft palate-lateral synechia syndrome

Blepharophimosis Everted lower lip vermilion Micrognathia

Autosomal dominant inheritance

Cleft palate-lateral synechia syndrome (CPLS) is a congenital malformation syndrome characterized by the association of cleft palate and intra-oral lateral synechiae connecting the free borders of the palate and the floor of the mouth. CPLS is presumed to be inherited in an autosomal dominant manner.

530
(69.7%)

Microcephaly-deafness-intellectual disability syndrome

Epicanthus Everted lower lip vermilion Micrognathia

Autosomal dominant inheritance

Microcephaly-deafness-intellectual disability syndrome is characterised by microcephaly, deafness, intellectual deficit and facial dysmorphism (facial asymmetry, prominent glabella, low-set and cup-shaped ears, protruding lower lip, micrognathia). It has been described in a mother and her son. The mode of inheritance is probably autosomal dominant.

530
(69.7%)

Non-distal trisomy 10q

Downslanted palpebral fissures Everted lower lip vermilion Micrognathia

Non-distal trisomy 10q is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 10, characterized by mild to moderate developmental delay, postnatal growth retardation, central hypotonia, craniofacial dysmorphism (incl. microcephaly, prominent forehead, flat, thick ear helices, deep-set, small eyes, epicanthus, upturned nose, bow-shaped mouth, highly arched palate, micrognathia), ocular anomalies (e.g. iris coloboma, retinal dysplasia, strabismus), long, slender limbs and skeletal and digital anomalies (scoliosis, poly/syndactyly). Additional features reported include cardiac defects (e.g. septal ventricular defect), anal atresia, and cryptorchidism.

530
(69.7%)

Deafness-intellectual disability syndrome, Martin-Probst type

Epicanthus Micrognathia Thick lower lip vermilion

X-linked recessive inheritance

Deafness-intellectual disability syndrome, Martin-Probst type is characterised by severe bilateral deafness, intellectual deficit, umbilical hernia and abnormal dermatoglyphics. It has been described in three males from three generations of one family. Mild facial dysmorphism (telangiectasias, hypertelorism, dental anomalies and a wide nasal root) was also present. Short stature, pancytopaenia, microcephaly, and renal and genitourinary anomalies were present in some of the patients. The mode of transmission is X-linked recessive and the causative gene has been localised to the q1-21 region of the X chromosome.

530
(69.7%)

Distal trisomy 6p

Abnormal eyelash morphology Micrognathia Thin vermilion border

Distal trisomy of the short arm of chromosome 6 is characterized by pre- and postnatal growth retardation, a pattern of specific facial features (mostly of the eyes), microcephaly, and developmental delay.

530
(69.7%)

Craniosynostosis-anal anomalies-porokeratosis syndrome

Absent eyelashes Micrognathia Thick vermilion border

Autosomal recessive inheritance

Craniosynostosis - anal anomalies - porokeratosis, or CDAGS, is a very rare condition characterized by craniosynostosis and clavicular hypoplasia, (C), delayed closure of the fontanel (D), anal anomalies (A), genitourinary malformations (G) and skin eruption (S).

536
(69.7%)

Arterial tortuosity syndrome

Arachnodactyly Avascular necrosis of the capital femoral epiphysis Blepharophimosis Malar flattening Median cleft lip and palate

Autosomal recessive inheritance

A rare connective tissue disorder characterized by tortuosity and elongation of the large and medium-sized arteries and a propensity towards aneurysm formation, vascular dissection, and stenosis of the pulmonary arteries.

537
(69.6%)

Angel-shaped phalango-epiphyseal dysplasia

Hypodontia Short 1st metacarpal Short middle phalanx of the 5th finger

Autosomal dominant inheritance

A form of acromelic dysplasia characterized by the distinctive radiological sign of angel-shaped middle phalanges, a typical metacarpophalangeal pattern profile (mainly affecting first metacarpals and middle phalanges of second, third and fifth digits, which all appear short), epiphyseal changes in the hips and, in some, abnormal dentition and delayed bone age.

537
(69.6%)

Carpenter syndrome

Broad thumb Hypodontia Short finger

Carpenter syndrome is a subtype of a family of genetic disorders known as acrocephalopolysyndactyly (ACPS) disorders.

539
(69.6%)

Xq27.3q28 duplication syndrome

Short foot Small hand Thin vermilion border

X-linked recessive inheritance

Xq27.3q28 duplication syndrome is a recently described syndrome characterized by short stature, hypogonadism, developmental delay and facial dysmorphism.

540
(69.6%)

Waardenburg syndrome

Abnormal lip morphology Telecanthus Tetraphocomelia

Waardenburg syndrome (WS) is a disorder characterized by varying degrees of deafness and minor defects in structures arising from neural crest, including pigmentation anomalies of eyes, hair, and skin. WS is classified into four clinical and genetic phenotypes.

541
(69.6%)

Multiple sulfatase deficiency

Broad thumb Microcephaly Smooth philtrum Thick eyebrow

Autosomal recessive inheritance

Multiple sulfatase deficiency (MSD) is a very rare and fatal lysosomal storage disease characterized by a clinical phenotype that combines the features of different sulfatase deficiencies (whether lysosomal or not) that can have neonatal (most severe), infantile (most common) and juvenile (rare) presentations with manifestations including hypotonia, coarse facial features, mild deafness, skeletal anomalies, ichthyosis, hepatomegaly, developmental delay, progressive neurologic deterioration and hydrocephalus.

542
(69.5%)

Prader-Willi-like syndrome

Acromesomelia Almond-shaped palpebral fissure Open mouth Short foot Small hand

Prader-Willi-like syndrome is a rare, genetic, endocrine disease characterized by manifestations of a Prader-Willi syndrome phenotype (including obesity, hyperphagia, hypotonia, psychomotor delay, intellectual disability, small hands/feet, hypogonadism, growth hormone deficiency and characteristic facial features) ocurring in the absence of 15q11-q13 genomic abnormalities.

542
(69.5%)

Cartilage-hair hypoplasia

Abnormal palate morphology Epicanthus Micromelia Short palm

Autosomal recessive inheritance

Cartilage-hair hypoplasia is a disease affecting the bone metaphyses causing small stature from birth.

542
(69.5%)

Prader-Willi syndrome

Downslanted palpebral fissures Hemiatrophy High palate Short palm

Sporadic

Prader-Willi syndrome is a rare genetic disorder characterized by hypothalamic-pituitary abnormalities with severe hypotonia during the neonatal period and first two years of life and the onset of hyperphagia with a risk of morbid obesity during infancy and adulthood, learning difficulties and behavioral problems or severe psychiatric problems.

545
(69.5%)

Ear-patella-short stature syndrome

Micrognathia Narrow mouth Patellar aplasia Thick vermilion border

Ear-patella-short stature syndrome is an association of malformations including bilateral microtia (severe hypoplasia of ear pinnae), absent patellae, short stature, poor weight gain, and characteristic facial features such as high forehead, micrognathism with full lips and small mouth, and accentuated nasolabial folds (smile wrinkles linking the nostrils to the labial commissure).

546
(69.4%)

Beckwith-Wiedemann syndrome

Cleft palate Mandibular prognathia Short femur Wide mouth

Autosomal dominant inheritance

Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by overgrowth, tumor predisposition and congenital malformations.

547
(69.4%)

Microcephalic osteodysplastic primordial dwarfism type II

Brachydactyly Downslanted palpebral fissures Microdontia Micromelia Retrognathia

Autosomal recessive inheritance

'Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is a form of microcephalic primordial dwarfism (MPD; see this term) characterized by severe pre- and postnatal growth retardation, with marked microcephaly in proportion to body size, skeletal dysplasia, abnormal dentition, insulin resistance, and increased risk for cerebrovascular disease.'

548
(69.4%)

Joubert syndrome with Jeune asphyxiating thoracic dystrophy

Brachydactyly Epicanthus Micrognathia Rhizomelic arm shortening

Joubert syndrome with Jeune asphyxiating thoracic dystrophy (JATD) is an extremely rare genetic bone disorder characterized by the classic features of Joubert syndrome (i.e. malformation of the brainstem causing ataxia, hypotonia,cognitive impairment, and abnormal eyemovements), associated with the skeletal anomalies found in JATD including short-rib dysplasia and narrow thorax causing respiratory failure, short limbs, and metaphyseal changes.

549
(69.4%)

Craniosynostosis, Herrmann-Opitz type

Brachydactyly Cleft palate Micrognathia Micromelia

Craniosynostosis, Herrmann-Opitz type is a rare bone development disorder characterized by intellectual disability, short stature, turribrachycephaly, facial dysmorphism (i.e. severe hypertelorism, hypoplasia of supraorbital ridges, abnormal ears, and micrognathia), bony defects of the occiput, and digital anomalies (incl. syndactyly, oligodactyly, and/or brachydactyly). Urethral atresia has also been reported. There have been no further descriptions in the literature since 1987.

550
(69.4%)

Spondyloepiphyseal dysplasia tarda

Hypoplasia of the odontoid process Short neck Upper limb undergrowth

Spondyloepiphyseal dysplasia tarda (SEDT) is characterized by disproportionate short stature in adolescence or adulthood, associated with a short trunk and arms and barrel-shaped chest.

551
(69.3%)

Edinburgh malformation syndrome

Micrognathia Slender finger Synophrys Thin vermilion border

Autosomal dominant inheritance

Edinburgh malformation syndrome is a rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by consistently abnormal facial appearance, true or apparent hydrocephalus, motor and cognitive developmental delay, failure to thrive (feeding difficulties, vomiting, chest infections) and death within a few months of birth. Carp mouth, hairiness of the forehead, neonatal hyperbilirubinemia and advanced bone age may also be associated. There have been no further descriptions in the literature since 1991.

551
(69.3%)

12q14 microdeletion syndrome

Clinodactyly of the 5th finger Micrognathia Thick eyebrow Thin vermilion border

12q14 microdeletion syndrome is characterised by mild intellectual deficit, failure to thrive, short stature and osteopoikilosis. It has been described in four unrelated patients. The syndrome appears to be caused by a heterozygous deletion at chromosome region 12q14, which was detected in three of the four patients. The deleted region contains the LEMD3 gene: mutations in this gene have already been implicated in osteopoikilosis.

553
(69.3%)

Paternal 20q13.2q13.3 microdeletion syndrome

Aplasia/Hypoplasia of the eyebrow Micrognathia Short philtrum

Paternal 20q13.2q13.3 microdeletion syndrome is a recently described syndrome characterized by severe pre- and post-natal growth retardation, microcephaly, intractable feeding difficulties, mild psychomotor retardation, hypotonia and facial dysmorphism.

554
(69.3%)

Summitt syndrome

Epicanthus Narrow face Short 4th metacarpal Short palm

Autosomal recessive inheritance

Summitt syndrome is an extremely rare disorder originally described in two brothers and characterized by mild to severe craniosynostosis and syndactyly, obesity, and normal intelligence. Acrocephaly, brachydactyly, clinodactyly, mild syndactyly of the hands and feet, genu valgum and marked obesity were later described in another patient. There have been no further descriptions in the literature since 1979. Summitt syndrome could be a variant of Carpenter syndrome.

554
(69.3%)

Chondrodysplasia-disorder of sex development syndrome

Micromelia Short metacarpal Telecanthus

Autosomal recessive inheritance

Chondrodysplasia - disorder of sex development is an extremely rare disorder of sex development (see this term), reported in only two siblings (one terminated in pregnancy) to date, characterized by the clinical features of 46,XY complete gonadal dysgenesis (see this term; normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) in association with severe dwarfism with generalized chondrodysplasia (bell-shaped thorax, micromelia, brachydactyly). Other reported features in the live sibling included eye anomalies (hypoplastic irides, myopia, coloboma of optic discs), dysmorphic features (deep-set eyes, upslanting palpebral fissures, puffy eyelids, large ears and mouth, mild prognathism), muscular hypoplasia, mild intellectual deficiency and severe microcephaly with cerebellar vermis hypoplasia. An autosomal recessive inheritance has been suggested.

556
(69.3%)

Toriello-Carey syndrome

Brachydactyly Pierre-Robin sequence Retrognathia Telecanthus

Autosomal recessive inheritance

Toriello Carey syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysmorphic features, cerebral anomalies, swallowing difficulties, cardiac defects and hypotonia.

557
(69.2%)

Townes-Brocks syndrome

Aplasia/Hypoplasia of the 3rd toe Blepharophimosis Broad thumb Wide mouth

A rare genetic disorder characterized by the triad of imperforate anus, dysplastic ears often associated with sensorineural and/or conductive hearing impairment, and thumb malformations. These features are often associated with other signs mainly affecting the kidneys and heart.

558
(69.2%)

Marshall-Smith syndrome

Large hands Micrognathia Open mouth Shallow orbits Slender long bone

Autosomal dominant inheritance Sporadic

Marshall-Smith syndrome is a rare genetic disease characterized by tall stature and advanced bone age at birth.

559
(69.2%)

Robinow syndrome

Brachydactyly Cleft lip Frontal bossing Mesomelia Retrognathia

Robinow syndrome (RS) is a rare genetic syndrome characterized by limb shortening and abnormalities of the head, face and external genitalia.

560
(69.2%)

Mesomelic dwarfism-cleft palate-camptodactyly syndrome

Abnormal metacarpal morphology Camptodactyly of finger Cleft palate Retrognathia Thin vermilion border

Autosomal recessive inheritance

A rare syndrome characterised by mesomelic shortening and bowing of the limbs, camptodactyly, skin dimpling and cleft palate with retrognathia and mandibular hypoplasia. It has been described in a brother and sister born to consanguineous parents. Transmission is autosomal recessive.

561
(69.1%)

Brachydactyly type E

Round face Short distal phalanx of finger Short metatarsal

Brachydactyly type E (BDE) is a congenital malformation of the digits characterized by variable shortening of the metacarpals with more or less normal length phalanges, although the terminal phalanges are often short.

562
(69.1%)

Facial dysmorphism-shawl scrotum-joint laxity syndrome

Cubitus valgus Epicanthus Genu valgum Mandibular prognathia Smooth philtrum

Facial dysmorphism-shawl scrotum-joint laxity syndrome is characterised by facial dysmorphism (hypertelorism, telecanthus, downslanting palpebral fissures, ptosis, malar hypoplasia, broad nasal bridge, thin upper lip, smooth philtrum, and low-set prominent ears) and associated with joint anomalies (genu valgum or cubitus valgus, hyper-extensible joints, etc.). It has been described in two patients (a mother and her son). The boy also had hypoplastic shawl scrotum and cryptorchidism, and the mother had mild intellectual deficit.

563
(69.1%)

Keppen-Lubinsky syndrome

Micrognathia Shallow orbits Short philtrum

Autosomal dominant inheritance

A rare, genetic, primary lipodystrophy syndrome characterized by severe developmental delay and intellectual disability, hypertonia, hyperreflexia, microcephaly, tightly adherent skin, an aged appearance, severe generalized lipodystrophy, and distinct facial dysmorphism which includes large prominent eyes, narrow nasal bridge, tented upper lip vermilion, an open mouth, and high-arched palate. Laboratory analysis of serum and urine are normal.

564
(69.1%)

X-linked intellectual disability, Stevenson type

Genu valgum Large hands Palpebral edema Tented upper lip vermilion Thick eyebrow

X-linked intellectual disability, Stevenson type is characterised by intellectual deficit, hypotonia, absent deep tendon reflexes, tapered fingers and excessive fingerprint arches, genu valgum, a characteristic face and small teeth. It has been described in four males from two generations of one family. The causative gene appears to be located in the q13 region of the X chromosome.

565
(69.1%)

X-linked intellectual disability with marfanoid habitus

Abnormality of the dentition Brachydactyly Micrognathia Short philtrum

X-linked recessive inheritance

The Lujan-Fryns syndrome or X-linked mental retardation (XLMR) with marfanoid habitus syndrome is a syndromic X-linked form of intellectual disability, associated with tall, marfanoid stature, distinct facial dysmorphism and behavioral problems.

566
(69.1%)

FATCO syndrome

Absent hand Fibular aplasia Fibular hypoplasia Split hand

A rare, genetic, congenital limb malformation syndrome characterized by unilateral or bilateral fibular aplasia/hypoplasia, tibial campomelia, and lower limb oligosyndactyly involving the lateral rays. Upper limb oligosyndactyly and cleft lip/palate may also be associated.

566
(69.1%)

Metaphyseal dysostosis-intellectual disability-conductive deafness syndrome

Recurrent otitis media Short foot Short long bone Short palm

Autosomal recessive inheritance

Metaphyseal dysostosis-intellectual disability-conductive deafness syndrome is characterised by metaphyseal dysplasia, short-limb dwarfism, mild intellectual deficit and conductive hearing loss, associated with repeated episodes of otitis media in childhood. It has been described in three brothers born to consanguineous Sicilian parents. Variable manifestations included hyperopia and strabismus. The mode of inheritance is autosomal recessive.

568
(69.0%)

Ectopia cordis

Absent soft palate Bilateral cleft lip Micrognathia Phocomelia

569
(69.0%)

Schisis association

Cleft palate Micromelia Unilateral cleft lip

Schisis association describes the combination of two or more of the following anomalies: neural tube defects (e.g. anencephaly, encephalocele, spina bifida cystica), cleft lip/palate, omphalocele and congenital diaphragmatic hernia (see these terms). These anomalies are associated at a higher frequency than would be expected with random combination rates.

570
(69.0%)

Mandibulofacial dysostosis-microcephaly syndrome

Cleft palate Epicanthus Micrognathia Preaxial hand polydactyly

Autosomal dominant inheritance Autosomal recessive inheritance

Mandibulofacial dysostosis-microcephaly syndrome is a rare genetic multiple malformation disorder characterized by malar and mandibular hypoplasia, microcephaly, ear malformations with associated conductive hearing loss, distinctive facial dysmorphism, developmental delay, and intellectual disability.

570
(69.0%)

Mosaic trisomy 14

Blepharophimosis Camptodactyly of finger Cleft palate Micrognathia

Mosaic trisomy 14 is a rare chromosomal anomaly disorder, with a highly variable phenotype, principally characterized by growth and developmental delay, intellectual disability, body asymmetry/hypotonia, congenital heart defects, genitourinary abnormalities (cryptorchidism, micropenis, large clitoris, labial swelling), and abnormal skin hyperpigmentation. Patients usually present with craniofacial dysmorphism such as microcephaly, abnormal palpebral fissure, hypertelorism, ear abnormalities, broad nose, low-set ears, micro/retro-gnathia, and cleft or highly arched palate.

570
(69.0%)

Blepharophimosis-intellectual disability syndrome, SBBYS type

Blepharophimosis Clinodactyly of the 5th finger Micrognathia Submucous cleft hard palate

Autosomal dominant inheritance

Blepharophimosis-intellectual disability syndrome, SBBYS type is characterised by the association of congenital hypothyroidism, facial dysmorphism (microcephaly, blepharophimosis, a bulbous nose, thin lip, low-set ears and micrognathia), postaxial polydactyly and severe intellectual deficit. Less than 20 cases have been reported so far. Cryptorchidism is present in affected males. Some patients also have cardiac anomalies (interventricular communication), hypotonia and growth delay. Autosomal recessive inheritance has been suggested.

570
(69.0%)

Agammaglobulinemia-microcephaly-craniosynostosis-severe dermatitis syndrome

Arachnodactyly Cleft palate Epicanthus Micrognathia

Autosomal recessive inheritance

A syndrome that combines agammaglobulinemia with marked microcephaly, significant developmental delay, craniosynostosis, a severe dermatitis, cleft palate, narrowing of the choanae, and blepharophimosis. It has been described in three siblings, two males and one female, born to nonconsanguineous parents. Transmission is probably autosomal recessive. It has been suggested that this syndrome represents a new form of agammaglobulinemia due to a defect in early B-cell maturation.

570
(69.0%)

Mosaic variegated aneuploidy syndrome

Cleft palate Clinodactyly of the 5th finger Epicanthus Micrognathia

Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal anomaly characterized by multiple mosaic aneuploidies that leads to a variety of phenotypic abnormalities and cancer predisposition.

570
(69.0%)

Restrictive dermopathy

Camptodactyly of finger Downslanted palpebral fissures Micrognathia Submucous cleft hard palate

Autosomal dominant inheritance Autosomal recessive inheritance Heterogeneous

A congenital genodermatosis with skin/mucosae involvement, characterized by very tight and thin skin with erosions and scaling, associated to a typical facial dysmorphism, arthrogryposis multiplex, fetal akinesia or hypokinesia deformation sequence (FADS) and pulmonary hypoplasia without neurological abnormalities.

576
(68.9%)

Microgastria-limb reduction defect syndrome

Abnormality of the radius Aplastic clavicle Frontal bossing Short thumb

Sporadic

Microgastria-limb reduction defect syndrome is a rare multiple congenital anomalies syndrome characterized by congenital microgastria and a uni- or bilateral limb reduction defect, that can include absent or hypoplastic thumbs, radius, ulna and/or amelia. Association with other variable abnormalities, including intestinal malrotation, asplenia, dysplastic kidneys, hypoplastic lungs, dysplastic corpus collosum, and abnormal genitalia, has been reported.

577
(68.9%)

Skeletal dysplasia-epilepsy-short stature syndrome

Abnormality of the dentition Mandibular prognathia Short distal phalanx of finger

Autosomal recessive inheritance

Skeletal dysplasia-epilepsy-short stature syndrome is characterized by moderate to severe intellectual deficit, seizures, short stature, and skeletal dysplasia. It has been described in seven patients. Other manifestations can be associated (retinal abnormalities, brachydactyly, prognathism, dental malocclusion). It is transmitted as an autosomal recessive trait.

577
(68.9%)

Albers-Schönberg osteopetrosis

Abnormality of the dentition Mandibular osteomyelitis Short distal phalanx of finger

Autosomal dominant inheritance Heterogeneous

A sclerosing disorder of the skeleton characterized by increased bone density that classically displays the radiographic sign of ''sandwich vertebrae'' (dense bands of sclerosis parallel to the vertebral endplates).

579
(68.9%)

Lethal Kniest-like dysplasia

Brachydactyly Cleft palate Mesomelic/rhizomelic limb shortening Short ribs

Autosomal recessive inheritance

A rare, lethal, congenital, chondrodysplasia disorder characterized by dumbbell-shaped long bones with markedly shortened diaphyses and metaphyseal irregularities associated with a "Swiss cheese" appearance of the cartilage matrix, as well as distinctive changes in the growth plate and resting cartilage, resulting in death in the neonatal period. There have been no further descriptions in the literature since 1983.

580
(68.9%)

Hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome

Bifid uvula Broad thumb Contracture of the proximal interphalangeal joint of the 5th finger Highly arched eyebrow Micrognathia

Hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome is a rare, non-acquired pituitary hormone deficiency syndrome characterized by severe, congenital microcephaly, facial dysmorphism (highly arched eyebrows, hypertelorism, convex nasal ridge, protruding ears with underdeveloped superior antihelix crus, micrognathia), bilateral sensorineural deafness and hypogonadotropic hypogonadism, in association with early feeding problems, myopia, moderate intellectual disability and moderate short stature.

581
(68.9%)

Dyschondrosteosis-nephritis syndrome

Aplasia/Hypoplasia of the radius Microdontia Micromelia Radial bowing

Autosomal dominant inheritance

Dyschondrosteosis - nephritis is characterized by the association of short stature due to mesomelic shortening of the limbs and Madelung deformity (see this term), with hereditary nephritis.

582
(68.9%)

Kleefstra syndrome

Long philtrum Mandibular prognathia Talipes equinovarus Upslanted palpebral fissure

Kleefstra syndrome (KS) is a genetic disorder characterized by intellectual disability, childhood hypotonia, severe expressive speech delay and a distinctive facial appearance with a spectrum of additional clinical features.

583
(68.8%)

Autosomal recessive distal osteolysis syndrome

Abnormality of the dentition Hypoplasia of the maxilla Short distal phalanx of finger

Autosomal recessive inheritance

An early-onset distal osteolysis characterised by severe resorption of the hands and feet and absence of the distal and middle phalanges. It has been described in a son and daughter born to consanguineous parents. Other manifestations include distal muscular hypertrophy, flexion contractures, short stature, mild intellectual deficit and characteristic facies (maxillary hypoplasia, exophthalmos, and a broad nasal tip). It is transmitted as an autosomal recessive trait.

584
(68.8%)

19q13.11 microdeletion syndrome

Clinodactyly of the 5th finger Retrognathia Sparse or absent eyelashes Thin vermilion border

Autosomal dominant inheritance

The 19q13.11 microdeletion is characterized by several major features including pre and postnatal growth retardation, slender habitus, severe postnatal feeding difficulties, microcephaly, intellectual deficit with speech disturbance, hypospadias and ectodermal dysplasia presented by scalp aplasia, thin and sparse hair, eyebrows and eyelashes, thin and dry skin and dysplasic nails.

585
(68.8%)

2q24 microdeletion syndrome

Downslanted palpebral fissures Hand clenching Short neck Short philtrum

2q24 microdeletion syndrome is a chromosomal anomaly consisting of a partial long arm deletion of chromosome 2 and characterized clinically by a wide range of manifestations (depending on the specific region deleted) which can include seizures, microcephaly, dysmorphic features, cleft palate, eye abnormalities (coloboma, cataract and microphthalmia), growth retardation, failure to thrive, heart defects, limb anomalies, developmental delay and autism.

586
(68.8%)

Infantile spasms-broad thumbs syndrome

Broad thumb Convex nasal ridge Downslanted palpebral fissures Micrognathia

Infantile spasms-broad thumbs syndrome is a rare neurologic disorder characterized by profound developmental delay, facial dysmorphism (i.e. microcephaly, large anterior fontanel, hypertelorism, downslanting palpebral fissures, beaked nose, micrognathia), broad thumbs and flexion and/or extension spasms. Bilateral cataracts, hypertrophic cardiomyopathy and hydrocele have also been reported. EEG shows hypsarrhythmic features and MRI may reveal partial agenesis of the corpus callosum, mild brain atrophy and/or ventriculomegaly. There have been no further descriptions in the literature since 1990.

587
(68.7%)

Holt-Oram syndrome

Absent thumb Depressed nasal bridge Micrognathia Radioulnar synostosis

Autosomal dominant inheritance

A genetic syndrome with limb reduction defects characterized by skeletal abnormalities of the upper limbs and mild-to-severe congenital cardiac defects.

588
(68.7%)

Arachnoid cyst

Brachydactyly Distichiasis Hemiatrophy Tongue atrophy

Autosomal recessive inheritance

A disorder with extraparenchymal cysts, intra-arachnoidal collections of fluid, the composition of which is close to that of cerebrospinal fluid. They are often asymptomatic.

589
(68.7%)

Osteosarcoma

Absent thumb Chemosis Hypodontia

Osteosarcoma is a primary malignant tumour of the skeleton characterised by the direct formation of immature bone or osteoid tissue by the tumour cells.

590
(68.7%)

Aspartylglucosaminuria

Abnormality of the ulna Macroglossia Mandibular prognathia Thick vermilion border

Autosomal recessive inheritance

An autosomal recessive lysosomal storage disease belonging to the oligosaccharidosis group (also called glycoproteinosis).

591
(68.7%)

Cutis marmorata telangiectatica congenita

Micrognathia Oral cleft Short lower limbs

Autosomal recessive inheritance

Cutis marmorata telangiectatica congenita (CMTC) is a congenital localized or generalized vascular anomaly characterized by a persistent cutis marmorata pattern with a marbled bluish to deep purple appearance, spider nevus-like telangiectasia, phlebectasia and, occasionally, ulceration and atrophy of the affected skin.

592
(68.5%)

48,XYYY syndrome

Epicanthus Long philtrum Radioulnar synostosis Short neck

48,XYYY syndrome is a rare Y chromosome number anomaly that affects only males and is characterized by mild-moderate developmental delay (especially speech), normal to mild intellectual disability, large, irregular teeth with poor enamel, tall stature and acne. Radioulnar synostosis and clinodactyly have also been associated. Boys generally present normal genitalia, while hypogonadism and infertility is frequently reported in adult males.

593
(68.5%)

Otospondylomegaepiphyseal dysplasia

Abnormal lacrimal duct morphology Cleft palate Micromelia

Otospondylomegaepiphyseal dysplasia (OSMED) is an inborn error of cartilage collagen formation characterized by sensorineural hearing loss, enlarged epiphyses, skeletal dysplasia with disproportionately short limbs, vertebral body anomalies and a characteristic facies.

594
(68.5%)

Zimmermann-Laband syndrome

Cleft palate Deep palmar crease Downslanted palpebral fissures Micrognathia Overtubulated long bones

Zimmermann-Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, coarse facial appearance, and absence or hypoplasia of nails or terminal phalanges of hands and feet.

595
(68.4%)

Distal monosomy 9p

Brachydactyly Cleft palate Epicanthus Trigonocephaly

Distal monosomy 9p is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the short arm of chromosome 9, with a highly variable phenotype typically characterized by intellectual disability, craniofacial dysmorphism (trigonocephaly, upslanting palpebral fissures, hypoplastic supraorbital ridges), abnormal digits (long middle phalanges with short distal phalanges), as well as frequent association with genitourinary abnormalities (cryptorchidism, hypospadias, ambiguous genitalia, 46,XY testicular dysgenesis). Congenital hypothyroidism and cardiovascular defects have been reported in some cases. Patients present an increased risk for gonadoblastoma.

596
(68.4%)

Distal monosomy 19p13.3

Arachnodactyly Hypoplasia of the maxilla Short philtrum Thick eyebrow

Distal monosomy 19p13.3 is a rare chromosomal anomaly associated with a wide range of phenotypic features depending on the size of the deletion. It may present with intrauterine growth retardation, failure to thrive, global developmental delay, dysmorphic features (such as broad forehead, midface retrusion, broad nasal bridge, micrognathia, smooth philtrum, low-set, dysplastic ears), congenital anomalies (such as atrial septal defect, gastrointestinal anomalies, renal and urogenital malformations, agenesis of the corpus callosum) and other clinical features (such as hearing loss, visual impairment and immune dysregulation).

597
(68.4%)

Multicentric carpo-tarsal osteolysis with or without nephropathy

Camptodactyly of finger Carpal osteolysis Downturned corners of mouth Micrognathia Telecanthus

Autosomal dominant inheritance

Idiopathic multicentric osteolysis is a very rare syndrome characterized by progressive loss of bone, usually the capsal and tarsal bones, resulting in deformity and disability, as well as chronic renal failure in many cases. The bone and renal disorders are sometimes associated with intellectual deficit and facial abnormalities.

598
(68.3%)

Persistent hyperplastic primary vitreous

Micrognathia Orbital cyst Small hand

599
(68.3%)

Branchiootic syndrome

Abnormal nasolacrimal system morphology Lip pit Micrognathia

Branchiootic syndrome is a rare, genetic multiple congenital anomalies syndrome characterized by second branchial arch anomalies (branchial cysts and fistulae), malformations of the outer, middle and inner ear associated with sensorineural, mixed or conductive hearing loss, and the absence of renal abnormalities. Typical ear findings consist of malformed auricles (e.g. lop or cupped ears), preauricular pits and/or tags, and middle and/or inner ear dysplasias (inculding cochlear, vestibular and semicircular channel hypoplasia, malformation of the ossicles and of middle ear space).

600
(68.2%)

X-linked intellectual disability, Siderius type

Cleft upper lip Large hands Scoliosis Synophrys

X-linked recessive inheritance

X-linked intellectual disability, Siderius type is characterised by mild to borderline intellectual deficit associated with cleft lip/palate. Preaxial polydactyly, large hands and cryptorchidism are sometimes present. The syndrome has been described in seven boys from two families. Transmission is X-linked and the syndrome is caused by mutations in the PHF8 gene, localised to the p11.21 region of the X chromosome.