401
(72.1%)

rhizomelic chondrodysplasia punctata type 1

Cleft palate Micrognathia Rhizomelia Upslanted palpebral fissure

Autosomal recessive inheritance

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems. The condition is caused by mutations in the PEX7 gene. It is inherited in an autosomal recessive pattern. Rhizomelic chondrodysplasia punctata type 1 is one of five types of rhizomelic chondrodysplasia punctata. The types have similar features and are distinguished by their genetic cause.

401
(72.1%)

desmosterolosis

Cleft palate Epicanthus Micrognathia Rhizomelia

Autosomal recessive inheritance

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

403
(72.1%)

autosomal recessive spondylometaphyseal dysplasia, Megarbane type

Deep philtrum Micromelia Round face Short long bone Short ribs

Autosomal recessive inheritance

Any spondylodysplastic dysplasia in which the cause of the disease is a mutation in the PAM16 gene.

404
(72.1%)

Cohen-Gibson syndrome

Broad thumb Epicanthus Large hands Retrognathia

Autosomal dominant inheritance

405
(72.0%)

MIRAGE syndrome

Overlapping fingers Radial club hand Recurrent urinary tract infections

Autosomal dominant inheritance

An autosomal dominant condition caused by mutation(s) in the SAMD9 gene, encoding sterile alpha motif domain-containing protein 9A. It is a syndromic condition comprising myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital abnormalities, and enteropathy.

406
(71.9%)

NEK9-related lethal skeletal dysplasia

Long philtrum Micrognathia Narrow palate Overlapping fingers

Autosomal recessive inheritance

NEK9-related lethal skeletal dysplasia is a rare, lethal, primary bone dysplasia characterized by fetal akinesia, multiple contractures, shortening of all long bones, short, broad ribs, narrow chest and thorax, pulmonary hypoplasia and a protruding abdomen. Short bowed femurs may also be associated.

407
(71.9%)

branchiogenic deafness syndrome

Short distal phalanx of finger Submucous cleft hard palate Trismus

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.

408
(71.9%)

Coffin-Siris syndrome 7

Brachydactyly Downslanted palpebral fissures Thin upper lip vermilion Trigonocephaly

Autosomal dominant inheritance

408
(71.9%)

autosomal recessive spinocerebellar ataxia 20

Brachydactyly Broad philtrum Epicanthus Relative macrocephaly

Autosomal recessive inheritance

Any autosomal recessive cerebellar ataxia in which the cause of the disease is a mutation in the SNX14 gene.

410
(71.9%)

apert syndrome

Broad distal phalanx of the thumb Cleft palate Downslanted palpebral fissures Mandibular prognathia Postaxial hand polydactyly

Autosomal dominant inheritance

Apert syndrome (AS) is a frequent form of acrocephalosyndactyly, a group of inherited congenital malformation disorders, characterized by craniosynostosis, midface hypoplasia, and finger and toe anomalies and/or syndactyly.

411
(71.9%)

microcephaly-capillary malformation syndrome

Cleft palate Hypoplasia of the maxilla Short distal phalanx of finger

Autosomal recessive inheritance

412
(71.8%)

syndromic X-linked intellectual disability Nascimento type

Short foot Thin vermilion border Upslanted palpebral fissure

X-linked recessive inheritance

X-linked intellectual disability, Nascimento type is a rare X-linked intellectual disability syndrome characterized by intellectual disability (with severe speech impairment), a myxedematous appearance, dysmorphic facial features (including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth with everted lower lip and downturned lip corners), low posterior hairline, short, broad neck, marked general hirsutism and abnormal hair whorls, skin changes (e.g. dry skin or hypopigmented spots), widely spaced nipples, obesity, micropenis, onychodystrophy and seizures.

412
(71.8%)

mitochondrial DNA depletion syndrome 13

Epicanthus Everted lower lip vermilion Short foot

Autosomal recessive inheritance

Any mitochondrial DNA depletion syndrome in which the cause of the disease is a mutation in the FBXL4 gene.

414
(71.8%)

ectodermal dysplasia syndrome with distinctive facial appearance and preaxial polydactyly of feet

Clinodactyly of the 5th finger Micrognathia Telecanthus Thin upper lip vermilion

Sporadic

414
(71.8%)

chromosome 5q12 deletion syndrome

Long fingers Long palpebral fissure Long philtrum Micrognathia

Autosomal dominant inheritance

PDE4D haploinsufficiency syndrome is a rare syndromic intellectual disability characterized by developmental delay, intellectual disability, low body mass index, long arms, fingers and toes, prominent nose and small chin.

414
(71.8%)

ectodermal dysplasia, sensorineural hearing loss, and distinctive facial features

Entropion Micrognathia Radial deviation of finger Short philtrum

Autosomal recessive inheritance

414
(71.8%)

distal arthrogryposis type 2B1

Absent phalangeal crease Downslanted palpebral fissures Long philtrum Micrognathia

Autosomal dominant inheritance

414
(71.8%)

whistling face syndrome, recessive form

Epicanthus Long philtrum Micrognathia Ulnar deviation of finger

Autosomal recessive inheritance

414
(71.8%)

McDonough syndrome

Micrognathia Radial deviation of finger Short philtrum Upslanted palpebral fissure

Autosomal recessive inheritance

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.

414
(71.8%)

blepharophimosis - intellectual disability syndrome, Ohdo type

Clinodactyly of the 5th finger Epicanthus Micrognathia Smooth philtrum

Autosomal dominant inheritance

Ohdo blepharophimosis syndrome (OBS) is a multiple congenital malformation syndrome characterized by blepharophimosis, ptosis, dental hypoplasia, hearing impairment and intellectual disability.

414
(71.8%)

developmental delay, intellectual disability, obesity, and dysmorphic features

Epicanthus Micrognathia Short philtrum Tapered finger

Autosomal dominant inheritance

414
(71.8%)

arterial tortuosity syndrome

Arachnodactyly Downslanted palpebral fissures Long philtrum Micrognathia

Autosomal recessive inheritance

Arterial tortuosity syndrome (ATS) is 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.

414
(71.8%)

mandibulofacial dysostosis-microcephaly syndrome

Deep philtrum Epicanthus Micrognathia Preaxial hand polydactyly

Autosomal dominant 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.

414
(71.8%)

chromosome 2q32-q33 deletion syndrome

Arachnodactyly Downslanted palpebral fissures Micrognathia Smooth philtrum

Autosomal dominant inheritance

2q32q33 microdeletion syndrome is a recently described syndrome characterized by a variable phenotype involving moderate to severe intellectual deficit, significant speech delay, persistent feeding difficulties, growth retardation and dysmorphic features.

414
(71.8%)

chromosome 9p deletion syndrome

Epicanthus Micrognathia Tapered finger Thin upper lip vermilion

Autosomal dominant inheritance Sporadic

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

414
(71.8%)

mullerian derivatives-lymphangiectasia-polydactyly syndrome

Downslanted palpebral fissures Micrognathia Postaxial hand polydactyly Thin upper lip vermilion

Autosomal recessive inheritance

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

414
(71.8%)

3p- syndrome

Epicanthus Long philtrum Micrognathia Tapered finger

Autosomal dominant inheritance

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

414
(71.8%)

chromosome 19q13.11 deletion syndrome

Blepharophimosis Clinodactyly of the 5th finger Micrognathia Short philtrum

Autosomal dominant inheritance Sporadic

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.

414
(71.8%)

lathosterolosis

Epicanthus Micrognathia Postaxial hand polydactyly Thick upper lip vermilion

Autosomal recessive inheritance

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

414
(71.8%)

Wieacker-Wolff, X-linked recessive

Micrognathia Proximal placement of thumb Smooth philtrum Upslanted palpebral fissure

X-linked recessive inheritance

A severe X-linked recessive neurodevelopmental disorder characterized by severe contractures (arthrogryposis) and intellectual disability.

414
(71.8%)

Miller-Dieker lissencephaly syndrome

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

Autosomal dominant inheritance Contiguous gene syndrome

A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.

414
(71.8%)

distal 10q deletion syndrome

Epicanthus Micrognathia Radial deviation of finger Thin upper lip vermilion

Autosomal dominant inheritance Sporadic

Distal monosomy 10q is a chromosomal anomaly involving terminal deletion of the long arm of chromosome 10 and is characterized by facial dysmorphism, pre- and postnatal growth retardation, cardiac and genital anomalies, and developmental delay.

414
(71.8%)

Ehlers-Danlos syndrome, musculocontractural type 1

Arachnodactyly Downslanted palpebral fissures Microretrognathia Thin upper lip vermilion

Autosomal recessive inheritance

414
(71.8%)

Renpenning syndrome

Clinodactyly of the 5th finger Epicanthus Micrognathia Thin upper lip vermilion

X-linked recessive inheritance

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

414
(71.8%)

oculocerebrofacial syndrome, Kaufman type

Clinodactyly of the 5th finger Epicanthus Micrognathia Thin upper lip vermilion

Autosomal recessive inheritance

414
(71.8%)

cardiofaciocutaneous syndrome 1

Deep philtrum Epicanthus Hyperextensibility of the finger joints Micrognathia

Autosomal dominant inheritance

Any cardiofaciocutaneous syndrome in which the cause of the disease is a mutation in the BRAF gene.

437
(71.8%)

Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis

Arachnodactyly Long philtrum Malar flattening Ulnar bowing

Autosomal dominant inheritance

438
(71.8%)

terminal osseous dysplasia-pigmentary defects syndrome

Brachydactyly Cleft palate Epicanthus Mesomelic leg shortening Short toe

X-linked dominant inheritance

Terminal osseous dysplasia-pigmentary defects syndrome is characterised by malformation of the hands and feet, pigmentary skin lesions on the face and scalp and digital fibromatosis.

439
(71.8%)

alpha thalassemia-X-linked intellectual disability syndrome

Absent frontal sinuses Epicanthus Tapered finger U-Shaped upper lip vermilion

X-linked dominant inheritance

X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal.

440
(71.7%)

Ruvalcaba syndrome

Dental crowding Downslanted palpebral fissures Short foot Short metatarsal Short palm

Autosomal dominant inheritance

Ruvalcaba syndrome is an extremely rare malformation syndrome, described in less than 10 patients to date, characterized by microcephaly with characteristic facies (downslanting parpebral fissures, microstomia, beaked nose, narrow maxilla), very short stature, narrow thoracic cage with pectus carinatum, hypoplastic genitalia and skeletal anomalies (i.e. characteristic brachydactyly and osteochondritis of the spine) as well as intellectual and developmental delay.

441
(71.7%)

Kleefstra syndrome 1

Brachydactyly Mandibular prognathia Single transverse palmar crease U-Shaped upper lip vermilion Upslanted palpebral fissure

Autosomal dominant inheritance Sporadic

An autosomal dominant non-syndromic intellectual disability that has material basis in an autosomal dominant mutation of EHMT1 on chromosome 9q34.3.

442
(71.6%)

X-linked intellectual disability with marfanoid habitus

Arachnodactyly Broad thumb Micrognathia Open mouth Thin upper lip vermilion

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.

443
(71.5%)

Nijmegen breakage syndrome

Cleft upper lip Micrognathia Upslanted palpebral fissure

Autosomal recessive inheritance

Nijmegen breakage syndrome is a rare genetic disease presenting at birth with microcephaly, dysmorphic facial features, becoming more noticeable with age, growth delay, and later-onset complications such as malignancies and infections.

443
(71.5%)

autosomal dominant Opitz G/BBB syndrome

Cleft upper lip Epicanthus Micrognathia

Autosomal dominant inheritance

Autosomal dominant form of Opitz G/BBB syndrome.

445
(71.4%)

chondrodysplasia with joint dislocations, gPAPP type

Cleft palate Micrognathia Narrow mouth Short metacarpal

Autosomal recessive inheritance

446
(71.4%)

metaphyseal dysostosis-intellectual disability-conductive deafness syndrome

Carpal bone hypoplasia Recurrent otitis media Short long bone Short ribs

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.

447
(71.3%)

spondylomegaepiphyseal dysplasia with upper limb mesomelia, punctate calcifications, and deafness

Brachydactyly Distal ulnar epiphyseal stippling Sensorineural hearing impairment Short foot

Sporadic

448
(71.3%)

MMEP syndrome

Blepharophimosis Cleft upper lip Mandibular prognathia Split foot

Autosomal dominant inheritance

A congenital syndromic form of split-hand/foot malformation (SHFM). It is characterized by microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. MMEP syndrome is considered to be a very rare condition, although the exact prevalence remains unknown. The etiology is not completely understood. Disruption of the sorting nexin 3 gene (SNX3; 6q21) has been shown to play a causative role in MMEP, although this was not confirmed in recent studies.

449
(71.3%)

fibrodysplasia ossificans progressiva

Short 1st metacarpal Small cervical vertebral bodies Widely spaced teeth

Autosomal dominant inheritance

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites.

450
(71.3%)

microcephalic osteodysplastic dysplasia, Saul-Wilson type

Convex nasal ridge Micrognathia Short distal phalanx of finger Short metatarsal

Autosomal dominant inheritance

A bone development disease characterized by early developmental delay primarily involving speech, distinct facial features, short stature, brachydactyly, clubfoot deformities, cataracts, and microcephaly that has material basis in heterozygous mutation in COG4 on chromosome 16q22.1.

451
(71.2%)

Frank-Ter Haar syndrome

Downslanted palpebral fissures Micrognathia Short long bone Short phalanx of finger Wide mouth

Autosomal recessive inheritance

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

452
(71.2%)

external auditory canal atresia-vertical talus-hypertelorism syndrome

Epicanthus Short 5th finger

Autosomal dominant inheritance

452
(71.2%)

Fanconi anemia complementation group N

Epicanthus Short thumb

Autosomal recessive inheritance

Any Fanconi anemia in which the cause of the disease is a mutation in the PALB2 gene.

452
(71.2%)

holoprosencephaly, recurrent infections, and monocytosis

Epicanthus Short finger Short toe

Autosomal dominant inheritance

452
(71.2%)

Borjeson-Forssman-Lehmann syndrome

Blepharophimosis Coarse facial features Short toe Shortening of all middle phalanges of the fingers

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.

456
(71.2%)

microcephaly-cardiac defect-lung malsegmentation syndrome

Cleft palate Short distal phalanx of finger

Autosomal recessive inheritance

Microcephaly - cardiac defect - lung malsegmentation syndrome is a very rare syndrome characterized by the combination of microcephaly, heart defects, renal hypoplasia, lung segmentation defects and cleft palate.

456
(71.2%)

Diamond-Blackfan anemia 7

Cleft palate Short thumb

Autosomal dominant inheritance

Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL11 gene.

458
(71.2%)

nasopalpebral lipoma-coloboma syndrome

Broad forehead Clinodactyly of the 5th finger Hypoplasia of the maxilla Upper eyelid coloboma

Autosomal dominant inheritance

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

459
(71.2%)

congenital hypothalamic hamartoma syndrome

Median cleft lip Micrognathia Micromelia Postaxial hand polydactyly

Autosomal recessive inheritance

Hypothalamic hamartomas (HH) are rare, tumor-like malformations that occur during fetal development and are present at birth. The lesions usually do not change in size or spread to other locations. Both the type and severity of symptoms vary greatly among patients with hypothalamic hamartomas. Common symptoms include frequent gelastic seizures (spontaneous laughing, giggling and/or smirking) or dacrystic seizures (crying or grunting); developmental delays; and/or precocious puberty. Additional symptoms may include cognitive impairment; emotional and behavioral difficulties; and endocrine disturbances. These symptoms often start early in life but are frequently misdiagnosed. For some patients, endocrine (hormonal) disturbances such as central precocious puberty may be the only symptom. These patients can often be treated successfully with medications. For some, however, HH can be disabling. For those with HH and epilepsy, it is common for the disorder to progress and for different types of seizures to develop. The seizures associated with HH often cannot be well-controlled with the standard seizure medications. For some, additional treatment such as surgical removal, radiosurgery, or thermoablation may be indicated. Though hypothalamic hamartomas can occur in patients with certain genetic disorders (such as Pallister-Hall syndrome), the majority of cases are sporadic.

460
(71.1%)

lethal chondrodysplasia, Seller type

Absent ossification of calvaria Hypoplasia of the radius Hypoplasia of the ulna

Autosomal recessive inheritance

461
(71.1%)

short-rib thoracic dysplasia 10 with or without polydactyly

Brachydactyly Oral cleft Short long bone Short ribs

Autosomal recessive inheritance

An asphyxiating thoracic dystrophy that has material basis in homozygous or compound heterozygous mutation in the IFT172 gene on chromosome 2p23.

462
(71.1%)

fountain syndrome

Broad distal phalanx of finger Short palm Thick lower lip vermilion

Autosomal recessive inheritance

Fountain syndrome is an extremely rare multi-systemic genetic disorder characterized by intellectual disability, deafness, skeletal abnormalities and coarse facial features.

463
(71.0%)

faciocardiomelic syndrome

Long philtrum Micrognathia Slender long bone Telecanthus

Autosomal recessive inheritance

464
(71.0%)

cerebrooculofacioskeletal syndrome 1

Blepharophimosis Joint contracture of the hand Long philtrum Micrognathia

Autosomal recessive inheritance

Any COFS syndrome in which the cause of the disease is a mutation in the ERCC6 gene.

464
(71.0%)

d-bifunctional protein deficiency

Epicanthus Long philtrum Micrognathia Split hand

Autosomal recessive inheritance

D-bifunctional protein deficiency (DBP deficiency)is a genetic disorder that affects the ability of the body to effectively break down fat from our diet. It is typically characterized by hypotonia (low muscle tone) and seizures in the newborn period. Other symptoms include unusual facial features and an enlarged liver (hepatomegaly). Most babies with this condition nevergain anydevelopmental skills and do not survive past the age of 2. DBP deficiency is caused by mutations in the HSD17B4 gene and is inherited in an autosomal recessive manner. Some researchers have suggested classifying DBP deficiency into three subtypes, depending on how severely the mutation in the HSD17B4 gene affects the function of the gene and the protein that it codes for. Almost all individuals with types I, II, and III have similar signs and symptoms. A fourth subtype has additionally been proposed for individuals that have less severe symptoms. While there is no cure for DBP deficiency, treatment is focused on improving nutrition and growth, controlling symptoms, and limiting the progression of liver disease.

466
(71.0%)

intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

Brachydactyly Mandibular prognathia Open mouth Short philtrum

Autosomal dominant inheritance

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome is a rare, genetic, syndromic intellecutal disability disorder characterized by craniofacial dysmorphism (microcephaly, hypotonic facies, strabismus, long and flat malar region, posteriorly rotated ears, flat nasal bridge with broad nasal tip, short philtrum, thin vermillion border, open mouth with down-turned corners, high arched palate, pointed chin), global developmental delay, intellectual disability and variable neurobehavioral abnormalities (autism spectrum disorder, aggressivness, self injury). Additional features include vision abnormalities and variable sensorineural hearing loss, as well as short stature, hypotonia and gastrointestinal manifestations (e.g. poor feeding, gastroesophageal reflux, constipation).

467
(70.9%)

coxopodopatellar syndrome

Cleft palate Micrognathia Patellar hypoplasia Short femur

Autosomal dominant inheritance

Small patella syndrome (SPS) is a very rare benign bone dysplasia affecting skeletal structures of the lower limb and the pelvis.

467
(70.9%)

short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis

Cleft palate Microretrognathia Short femoral neck Short long bone

Autosomal recessive inheritance

469
(70.9%)

achondrogenesis type IA

Anteverted nares Hypoplasia of the radius Short ribs

Autosomal recessive inheritance

Achondrogenesis type 1A (ACG1A), a form of achondrogenesis, is a very rare, lethal skeletal dysplasia characterized by dwarfism with extremely short limbs, narrow chest, short ribs that are easily fractured, soft skull bones and distinctive histological features of the cartilage.

470
(70.8%)

chromosome 5p13 duplication syndrome

Brachycephaly Epicanthus Large hands Short philtrum

Sporadic

5p13 microduplication syndrome is a rare partial autosomal trisomy/tetrasomy characterized by global developmental delay, intellectual disability, autistic behavior, muscular hypotonia, macrocephaly and facial dysmorphism (frontal bossing, short palpebral fissures, low set, dysplastic ears, short or shallow philtrum, high arched or narrow palate, micrognathia). Other associated clinical features include sleep disturbances, seizures, aplasia/hypoplasia of the corpus callosum, skeletal abnormalities (large hands and feet, long fingers and toes, talipes).

470
(70.8%)

CHIME syndrome

Brachycephaly Epicanthus Large hands Palmoplantar hyperkeratosis Short philtrum

Autosomal recessive inheritance

CHIME syndrome is a rare ectodermal dysplasia syndrome characterized by ocular colobomas, cardiac defects, ichthyosiform dermatosis, intellectual disability, conductive hearing loss and epilepsy.

472
(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.

473
(70.8%)

spondylometaphyseal dysplasia, Sedaghatian type

Depressed nasal bridge Short finger Short long bone Short ribs

Autosomal recessive inheritance

Spondylometaphyseal dysplasia (SEMD), Sedaghatian type is a neonatal lethal form of spondylometaphyseal dysplasia characterized by severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly.

474
(70.8%)

robin sequence-oligodactyly syndrome

Cleft palate Hand oligodactyly Micrognathia

Autosomal dominant inheritance

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

475
(70.8%)

Costello syndrome

Epicanthus Hyperextensibility of the finger joints Micrognathia Thick lower lip vermilion

Autosomal dominant inheritance Sporadic

Costello syndrome (CS) is a rare multisystemic disorder characterized by failure to thrive, short stature, developmental delay or intellectual disability, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors.

476
(70.8%)

chromosome 4Q32.1-q32.2 triplication syndrome

Epicanthus Microretrognathia Short philtrum

Autosomal dominant inheritance

476
(70.8%)

intellectual disability, autosomal dominant 22

Epicanthus Micrognathia Thin upper lip vermilion

Autosomal dominant inheritance

Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the ZBTB18 gene.

476
(70.8%)

facial paresis, hereditary congenital, 3

Epicanthus Micrognathia Smooth philtrum

Autosomal recessive inheritance

Any congenital hereditary facial paralysis-variable hearing loss syndrome in which the cause of the disease is a mutation in the HOXB1 gene.

476
(70.8%)

blepharophimosis - intellectual disability syndrome, MKB type

Blepharophimosis Micrognathia Smooth philtrum

X-linked recessive inheritance

The Maat-Kievit-Brunner type of Ohdo syndrome is a rare condition characterized by intellectual disability and distinctive facial features. It has only been reported in males.

476
(70.8%)

chromosome 8q21.11 deletion syndrome

Epicanthus Micrognathia Short philtrum

Autosomal dominant inheritance Sporadic

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

476
(70.8%)

mandibulofacial dysostosis-macroblepharon-macrostomia syndrome

Downslanted palpebral fissures Micrognathia Smooth philtrum

Sporadic

476
(70.8%)

immunodeficiency 49

Micrognathia Short philtrum Upslanted palpebral fissure

Autosomal dominant inheritance

Any primary immunodeficiency disease in which the cause of the disease is a mutation in the BCL11B gene.

476
(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 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 in individuals with XY karyotype, and may be expressed as PCH only in individuals with XX karyotype.

476
(70.8%)

developmental and epileptic encephalopathy, 64

Epicanthus Micrognathia Thin upper lip vermilion

Autosomal dominant inheritance

476
(70.8%)

frontoocular syndrome

Epicanthus Micrognathia Narrow philtrum

Autosomal dominant inheritance

476
(70.8%)

7q11.23 microduplication syndrome

Long eyelashes Micrognathia Short philtrum

Autosomal dominant inheritance

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

476
(70.8%)

intellectual disability, X-linked, syndromic, bain type

Epicanthus Micrognathia Short philtrum

X-linked dominant inheritance

476
(70.8%)

chromosome 14q11-q22 deletion syndrome

Epicanthus Long philtrum Micrognathia

Sporadic

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

476
(70.8%)

intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency

Micrognathia Thin upper lip vermilion Upslanted palpebral fissure

Autosomal dominant inheritance

476
(70.8%)

syndromic X-linked intellectual disability Najm type

Epicanthus Long philtrum Micrognathia

X-linked dominant inheritance

Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development.

476
(70.8%)

lateral meningocele syndrome

Downslanted palpebral fissures Micrognathia Smooth philtrum

Autosomal dominant inheritance

476
(70.8%)

Potocki-Lupski syndrome

Downslanted palpebral fissures Micrognathia Smooth philtrum

Sporadic

17p11.2 microduplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 17, typically characterized by hypotonia, poor feeding, failure to thrive, developmental delay (particularly cognitive and language deficits), mild-moderate intellectual deficit, and neuropsychiatric disorders (behavioural problems, anxiety, attention deficit hyperactivity disorder, autistic spectrum disorder, bipolar disorder). Structural cardiovascular anomalies (dilated aortic root, bicommissural aortic valve, atrial/ventricular and septal defects) and sleep disturbance (obstructive and central sleep apnea) are also frequently associated.

476
(70.8%)

DiGeorge syndrome

Blepharophimosis Micrognathia Short philtrum

Autosomal dominant inheritance

A congenital anomaly characterized by immunodeficiency, abnormal facies, congenital heart disease, hypocalcemia, and increased susceptibility to infections. Pathologic characteristics include conotruncal abnormalities and absence or hypoplasia of thymus and parathyroid glands. DiGeorge syndrome is associated with abnormalities of chromosome 22. Also known as DiGeorge anomaly.

476
(70.8%)

Ogden syndrome

Epicanthus Microretrognathia Thick upper lip vermilion

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.

476
(70.8%)

mosaic variegated aneuploidy syndrome 1

Epicanthus Long philtrum Micrognathia

Autosomal recessive inheritance

Any mosaic variegated aneuploidy syndrome in which the cause of the disease is a mutation in the BUB1B gene.

476
(70.8%)

Emanuel syndrome

Long philtrum Micrognathia 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.

476
(70.8%)

autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Epicanthus Microretrognathia Thin upper lip vermilion

Autosomal dominant inheritance

498
(70.7%)

Fanconi anemia, complementation group W

Absent thumb Hypoplasia of the radius Midface retrusion

Autosomal recessive inheritance

499
(70.7%)

Ehlers-Danlos syndrome, spondylocheirodysplastic type

Bifid uvula Downslanted palpebral fissures Short metacarpal

Autosomal recessive inheritance

Ehlers-Danlos syndrome, spondylocheirodysplastic type is a subtype of Ehlers-Danlos syndrome characterized by skeletal dysplasia comprising platyspondyly with moderate short stature, osteopenia and widened metaphyses, in addition to hyperextensible, thin, easily bruised skin, hypermobility of small joints with tendency to contractures, prominent eyes with bluish sclerae, wrinkled palms, atrophy of the thenar muscle and tapering fingers.

500
(70.7%)

radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome

Diastema Hypoplasia of the radius

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.