Cleft Related Genetic Syndromes/Diseases

The following table was extracted from a table on Embryogenesis by Dr. Harold C. Slavkin; Director, National Institute of Dental & Craniofacial Research (NIDCR) :

TYPE (1)









ECM Collagen, type XI, alpha-2 chain COL11A2 6p21.3 120290 Stickler syndrome, type II 184840 AD cleft palate, micrognathia, glossoptosis, severe myopia, flat facies, dental anomalies, deafness
Osmed syndrome 215150 AR saddle nose, cleft palate, progressive deafness
Shprintzen-Goldberg syndrome 182212 AD craniosynostosis, microcephaly, maxillary and mandibular hypoplasia, palatal shelf soft tissue hypertrophy, cleft palate, prominant nose, narrow palpebral fissures
ECM Glypican-3 GPC3 Xq26 300037 Simpson dysmorphia syndrome 312870 X disproportionately large head, coarse facies, large protruding jaw, wide nasal bridge, upturned nasal tip, large mouth, thickened lips, central cleft of lower lip, midline groove of tongue and inferior alveolar ridge, enlarged tongue, short neck
ENZ Phenylalanine hydroxylase PAH 12q24.1 261600 Phenylketonuria 261600 AR microcephaly, occasional cleft palate, long simple philtrum, thin upper lip, flattened nasal bridge, epicanthus, upturned nose
IS Retinoblastoma-1 RB1 13q14.1-q14.2 180200 Retinoblastoma 180200 AD cleft palate, high forehead, prominent eyebrows, broad nasal bridge, bulbous tip of the nose, large mouth with thin upper lip, long philtrum, prominent earlobes
SEC Sonic hedgehog SHH 7q36 600725 Holoprosencephaly, type 3 142945 AD cyclopia, ocular hypotelorism, proboscis, midface hypoplasia, single nostril, midline cleft upper lip, premaxillary agenesis
TM Fibroblast growth factor receptor-2 FGFR2 10q26 176943 Crouzon craniofacial dysostosis 123500 AD craniosynostosis, parrot-beaked nose, short upper lip, hypoplastic maxilla, relative mandibular prognathism, shallow orbit
Jackson-Weiss syndrome 123150 AD craniosynostosis, midfacial hypoplasia
Apert syndrome 101200 AD craniosynostosis, brachysphenocephalic acrocephaly, flat facies, high narrow palate
Pfeiffer syndrome 101600 AD mild craniosynostosis, flat facies, acrocephaly
Beare-Stevenson cutis gyrata syndrome 123790 AD craniosynostosis, cloverleaf skull, cleft palate or uvula, craniofacial anomalies
TM Peroxisomal membrane protein-3 PXMP3 8q21.1 170993 Zellweger syndrome-3 170993 AD high forehead, dolichoturricephaly, large fontanels, flat face, round face, hypoplastic supraorbital ridge, epicanthus, cleft palate
TM Diastrophic dysplasia sulfate transporter DTDST 5q32-q33.1 222600 Diastrophic dysplasia 222600 AR hypertrophic auricular cartilage, cleft palate, micrognathia
          Neonatal osseous dysplasia I 256050 AR micrognathia, cleft palate, flat nasal bridge, mid-face hypoplasia, neonatal osseous dysplasia, lethal chondrodysplasia
TM Patched PTC 9q22.3 601309 Basal cell nevus syndrome (Gorlin syndrome) 109400 AD macrocephaly, broad facies, frontal and biparietal bossing, mild mandibular prognathism, odontogenic keratocysts of jaws, misshapen and/or carious teeth, cleft lip and palate, ectopic calcification of falx cerebri
TF Microphthalmia-associated transcription factor MITF 3p14.1-p12.3 156845 Waardenburg syndrome, type IIA 193510 AD wide nasal bridge, short philtrum, cleft lip or palate, deafness
          Pallister-Hall syndrome 146510 AD short nose, flat nasal bridge, multiple buccal frenula, microglossia, micrognathia, cleft palate, malformed ears
TF Paired box homeotic gene-3 PAX3 2q35 193500 Waardenburg syndrome, type I 193500 AD wide nasal bridge, short philtrum, cleft lip or palate, occasional deafness, dystopia canthorum
TF Sry (sex-determining region Y)-box 9 SOX9 17q24.3-q25.1 211970 Campomelic dysplasia 211970 AR small chondrocranium, large neurocranium, occasional platybasia, cleft palate, retroglossia, micrognathia, flat nasal bridge, malformed ears
TF Twist TWIST 7p21 601622 Saethre-Chotzen syndrome 101400 AD craniosynostosis, acrocephaly, brachycephaly, flat facies, thin long pointed nose, cleft palate, cranial asymmetry, ptosis, malformed ears
UNK DiGeorge syndrome chromosome region CATCH22 22q11 188400 DiGeorge syndrome 188400 AD low-set ears, short ears, small mouth, submucous or overt palatal cleft, cleft lip, bulbous nose, square nasal tip, short philtrum, micrognathia,
Velocardiofacial syndrome 192430 AD Pierre Robin syndrome, cleft palate, small open mouth, myopathic facies, retrognathia, prominent nose with squared-off nasal tip
UNK Treacle TCOF1 5q32-q33.1 154500 Treacher Collins mandibulofacial dysostosis 154500 AD malar hypoplasia, cleft palate, mandibular hypoplasia, macrostomia, malformed ears, sensorineural deafness, coloboma of lower eyelid


  1. CS; cytoskeletal protein, ECM; extracellular matrix protein; ENZ; enzyme, IS, intracellular signalling protein, NP; nuclear protein, SEC; secretory protein, TM; transmembrane protein, TF; transcription factor, UNK; unknown
  2. AD; autosomal dominant, AR; autosomal recessive, X; X-linked, XD; X-linked dominant, XR; X-linked recessive
  3. The following description is only a summary of the craniofacial features of the diseases and disorders. For detail information regarding defects in other affected tissues and organs, refer to the Online Mendelian Inheritance in Man (OMIM) at

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