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Orofacial cleft

MedGen UID:
472000
Concept ID:
C3266076
Congenital Abnormality
Synonyms: Oral cleft; Orofacial clefting
SNOMED CT: Orofacial cleft (449790007)
 
Related genes: TP63, SUMO1, MSX1, IRF6, BMP4
 
HPO: HP:0000202
Monarch Initiative: MONDO:0000358
OMIM® Phenotypic series: PS119530

Definition

The presence of a cleft (gap, opening, or groove) in the oral cavity, including cleft of the upper lip and/or cleft of the palate. Cleft of the upper lip is visible as a groove or fissure in the lip, most frequently due to a congenital failure of the maxillary and median nasal processes to fuse. Cleft palate is characterized by a grooved depression or fissure in the roof of the mouth, most often resulting from a congenital failure of the palate to fuse properly. Clefts of the lip and palate can occur individually or together. It is preferable to code each defect separately. [from HPO]

Conditions with this feature

5p partial monosomy syndrome
MedGen UID:
41345
Concept ID:
C0010314
Disease or Syndrome
Cri-du-chat syndrome was first described by Lejeune et al. (1963) as a hereditary congenital syndrome associated with deletion of part of the short arm of chromosome 5. The deletions can vary in size from extremely small and involving only band 5p15.2 to the entire short arm. Although the majority of deletions arise as new mutations, approximately 12% result from unbalanced segregation of translocations or recombination involving a pericentric inversion in one of the parents.
Oculoauriculovertebral spectrum with radial defects
MedGen UID:
67392
Concept ID:
C0220681
Disease or Syndrome
A rare branchial arches and limb primordia development disorder with characteristics of variable degrees of uni or bilateral craniofacial malformation and radial defects that result in extremely variable phenotypic manifestations. Characteristic features include low postnatal weight, short stature, vertebral defects, hearing loss, and facial dysmorphism (including facial asymmetry, external, middle and inner ear malformations, orofacial clefts, and mandibular hypoplasia). These features are invariably associated with radial defects, such as preaxial polydactyly, thumb and/or radius hypoplasia/agenesis, or triphalangeal thumb. Cardiac, pulmonary, renal, and central nervous system involvement has also been reported.
Smith-Magenis syndrome
MedGen UID:
162881
Concept ID:
C0795864
Disease or Syndrome
Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly coarse facial features that progress with age), developmental delay, cognitive impairment, behavioral abnormalities, sleep disturbance, and childhood-onset abdominal obesity. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory issues are frequently noted; these may include avoidant behavior, as well as repetitive seeking of textures, sounds, and experiences. Toileting difficulties are common. Significant anxiety is common as are problems with executive functioning, including inattention, distractibility, hyperactivity, and impulsivity. Maladaptive behaviors include frequent outbursts / temper tantrums, attention-seeking behaviors, opposition, aggression, and self-injurious behaviors including self-hitting, self-biting, skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. An underlying developmental asynchrony, specifically emotional maturity delayed beyond intellectual functioning, may also contribute to maladaptive behaviors in people with SMS.
Microphthalmia, syndromic 1
MedGen UID:
162898
Concept ID:
C0796016
Congenital Abnormality
Microphthalmia-ankyloblepharon-intellectual disability syndrome is characterized by microphthalmia, ankyloblepharon and intellectual deficit. It has been described in seven male patients from two generations of a Northern Ireland family. The causative gene is localized to the Xq27-q28 region. The syndrome is transmitted as an X-linked recessive trait.
MMEP syndrome
MedGen UID:
330469
Concept ID:
C1832440
Disease or Syndrome
A congenital syndromic form of split-hand/foot malformation with features of microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. MMEP syndrome is considered to be a very rare condition. Disruption of the sorting nexin 3 gene (SNX3; 6q21) has been shown to play a causative role in MMEP.
Chromosome 1p36 deletion syndrome
MedGen UID:
334629
Concept ID:
C1842870
Disease or Syndrome
The constitutional deletion of chromosome 1p36 results in a syndrome with multiple congenital anomalies and mental retardation (Shapira et al., 1997). Monosomy 1p36 is the most common terminal deletion syndrome in humans, occurring in 1 in 5,000 births (Shaffer and Lupski, 2000; Heilstedt et al., 2003). See also neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH; 616975), which shows overlapping features and is caused by heterozygous mutation in the RERE gene (605226) on proximal chromosome 1p36. See also Radio-Tartaglia syndrome (RATARS; 619312), caused by mutation in the SPEN gene (613484) on chromosome 1p36, which shows overlapping features.
Waardenburg syndrome type 1
MedGen UID:
376211
Concept ID:
C1847800
Disease or Syndrome
Waardenburg syndrome type I (WS1) is an auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin along with dystopia canthorum (lateral displacement of the inner canthi). The hearing loss in WS1, observed in approximately 60% of affected individuals, is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural. Most commonly, hearing loss in WS1 is bilateral and profound (>100 dB). The majority of individuals with WS1 have either a white forelock or early graying of the scalp hair before age 30 years. The classic white forelock observed in approximately 45% of individuals is the most common hair pigmentation anomaly seen in WS1. Affected individuals may have complete heterochromia iridium, partial/segmental heterochromia, or hypoplastic or brilliant blue irides. Congenital leukoderma is frequently seen on the face, trunk, or limbs.
Baraitser-Winter syndrome 1
MedGen UID:
340943
Concept ID:
C1855722
Disease or Syndrome
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability. Many (but not all) affected individuals have pachygyria that is predominantly frontal, wasting of the shoulder girdle muscles, and sensory impairment due to iris or retinal coloboma and/or sensorineural deafness. Intellectual disability, which is common but variable, is related to the severity of the brain malformations. Seizures, congenital heart defects, renal malformations, and gastrointestinal dysfunction are also common.
Craniosynostosis-intellectual disability-clefting syndrome
MedGen UID:
387829
Concept ID:
C1857472
Disease or Syndrome
A recessive syndrome characterized by craniosynostosis, intellectual disability, seizures, choroidal coloboma, dysplastic kidneys, bat ears, cleft lip and palate, and beaked nose.
ADULT syndrome
MedGen UID:
400232
Concept ID:
C1863204
Disease or Syndrome
The TP63-related disorders comprise six overlapping phenotypes: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome). Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3). Limb-mammary syndrome. Split-hand/foot malformation type 4 (SHFM4). Isolated cleft lip/cleft palate (orofacial cleft 8). Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling.
Holoprosencephaly 5
MedGen UID:
355304
Concept ID:
C1864827
Disease or Syndrome
Holoprosencephaly associated with mutations in the ZIC2 gene.
Tricho-oculo-dermo-vertebral syndrome
MedGen UID:
355714
Concept ID:
C1866427
Disease or Syndrome
4p partial monosomy syndrome
MedGen UID:
408255
Concept ID:
C1956097
Disease or Syndrome
Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008).
Microphthalmia, isolated, with coloboma 5
MedGen UID:
369356
Concept ID:
C1968843
Disease or Syndrome
Any microphthalmia, isolated, with coloboma in which the cause of the disease is a mutation in the SHH gene.
Gollop syndrome
MedGen UID:
444125
Concept ID:
C2931720
Disease or Syndrome
The features of frontofacionasal dysplasia include blepharophimosis, lower lid lagophthalmos, primary telecanthus, S-shaped palpebral fissures, facial hypoplasia, eyelid coloboma, widow's peak, cranium bifidum occultum, frontal lipoma, nasal hypoplasia, deformed nostrils, bifid nose, and cleft of lip, premaxilla, palate, and uvula (White et al., 1991). Also see frontonasal dysplasia (136760).
Baraitser-winter syndrome 2
MedGen UID:
482865
Concept ID:
C3281235
Disease or Syndrome
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability. Many (but not all) affected individuals have pachygyria that is predominantly frontal, wasting of the shoulder girdle muscles, and sensory impairment due to iris or retinal coloboma and/or sensorineural deafness. Intellectual disability, which is common but variable, is related to the severity of the brain malformations. Seizures, congenital heart defects, renal malformations, and gastrointestinal dysfunction are also common.
Short-rib thoracic dysplasia 10 with or without polydactyly
MedGen UID:
816505
Concept ID:
C3810175
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Autosomal dominant Robinow syndrome 1
MedGen UID:
1641736
Concept ID:
C4551475
Disease or Syndrome
Autosomal dominant Robinow syndrome (ADRS) is characterized by skeletal findings (short stature, mesomelic limb shortening predominantly of the upper limbs, and brachydactyly), genital abnormalities (in males: micropenis / webbed penis, hypoplastic scrotum, cryptorchidism; in females: hypoplastic clitoris and labia majora), dysmorphic facial features (widely spaced and prominent eyes, frontal bossing, anteverted nares, midface retrusion), dental abnormalities (including malocclusion, crowding, hypodontia, late eruption of permanent teeth), bilobed tongue, and occasional prenatal macrocephaly that persists postnatally. Less common findings include renal anomalies, radial head dislocation, vertebral abnormalities such as hemivertebrae and scoliosis, nail dysplasia, cardiac defects, cleft lip/palate, and (rarely) cognitive delay. When present, cardiac defects are a major cause of morbidity and mortality. A variant of Robinow syndrome, associated with osteosclerosis and caused by a heterozygous pathogenic variant in DVL1, is characterized by normal stature, persistent macrocephaly, increased bone mineral density with skull osteosclerosis, and hearing loss, in addition to the typical features described above.
Sandestig-stefanova syndrome
MedGen UID:
1718072
Concept ID:
C5394118
Disease or Syndrome
Sandestig-Stefanova syndrome (SANDSTEF) is an autosomal recessive developmental syndrome characterized by pre- and postnatal microcephaly, trigonocephaly, congenital cataract, microphthalmia, facial gestalt, camptodactyly, loss of periventricular white matter, thin corpus callosum, delayed myelinization, and poor prognosis (Sandestig et al., 2019).

Professional guidelines

PubMed

Mossey PA
Br Dent J 2023 Jun;234(12):953-957. Epub 2023 Jun 23 doi: 10.1038/s41415-023-5993-4. PMID: 37349453
Morales CZ, Wagner CS, Humphries LS, Vu GH, Kalmar CL, Bartlett SP, Taylor J, Swanson J
J Craniofac Surg 2022 Jul-Aug 01;33(5):1341-1345. Epub 2022 Jun 27 doi: 10.1097/SCS.0000000000008467. PMID: 35758434
Cash AC
Front Oral Biol 2012;16:111-23. Epub 2012 Jun 25 doi: 10.1159/000337665. PMID: 22759675

Recent clinical studies

Etiology

Marazita ML
Curr Top Dev Biol 2023;152:169-192. Epub 2022 Nov 14 doi: 10.1016/bs.ctdb.2022.10.006. PMID: 36707211
Spoyalo K, Courtemanche RJM, Henkelman E
Cleft Palate Craniofac J 2021 Apr;58(4):525-532. Epub 2020 Sep 15 doi: 10.1177/1055665620957215. PMID: 32929983
Ravel A, Mircher C, Rebillat AS, Cieuta-Walti C, Megarbane A
Arch Pediatr 2020 Jan;27(1):53-60. Epub 2019 Nov 26 doi: 10.1016/j.arcped.2019.11.008. PMID: 31784293
Duncan KM, Mukherjee K, Cornell RA, Liao EC
Dev Dyn 2017 Nov;246(11):897-914. Epub 2017 Sep 25 doi: 10.1002/dvdy.24566. PMID: 28795449Free PMC Article
Woo AS
Plast Reconstr Surg 2017 Jan;139(1):191e-203e. doi: 10.1097/PRS.0000000000002854. PMID: 28027255

Diagnosis

Jaruga A, Ksiazkiewicz J, Kuzniarz K, Tylzanowski P
Int J Mol Sci 2022 Jan 16;23(2) doi: 10.3390/ijms23020953. PMID: 35055138Free PMC Article
Ravel A, Mircher C, Rebillat AS, Cieuta-Walti C, Megarbane A
Arch Pediatr 2020 Jan;27(1):53-60. Epub 2019 Nov 26 doi: 10.1016/j.arcped.2019.11.008. PMID: 31784293
Society for Maternal-Fetal Medicine, Benacerraf BR, Bromley B, Jelin AC
Am J Obstet Gynecol 2019 Nov;221(5):B8-B12. doi: 10.1016/j.ajog.2019.08.050. PMID: 31679595
Phan M, Conte F, Khandelwal KD, Ockeloen CW, Bartzela T, Kleefstra T, van Bokhoven H, Rubini M, Zhou H, Carels CE
Hum Genet 2016 Dec;135(12):1299-1327. Epub 2016 Oct 3 doi: 10.1007/s00439-016-1733-z. PMID: 27699475Free PMC Article
Shkoukani MA, Lawrence LA, Liebertz DJ, Svider PF
Birth Defects Res C Embryo Today 2014 Dec;102(4):333-42. Epub 2014 Dec 10 doi: 10.1002/bdrc.21083. PMID: 25504820

Therapy

Fell M, Dack K, Chummun S, Sandy J, Wren Y, Lewis S
Cleft Palate Craniofac J 2022 Sep;59(9):1185-1200. Epub 2021 Sep 27 doi: 10.1177/10556656211040015. PMID: 34569861Free PMC Article
Dardani C, Howe LJ, Mukhopadhyay N, Stergiakouli E, Wren Y, Humphries K, Davies A, Ho K, Weinberg SM, Marazita ML, Mangold E, Ludwig KU, Relton CL, Davey Smith G, Lewis SJ, Sandy J, Davies NM, Sharp GC
Int J Epidemiol 2020 Aug 1;49(4):1282-1293. doi: 10.1093/ije/dyaa047. PMID: 32373937Free PMC Article
Suhl J, Leonard S, Weyer P, Rhoads A, Siega-Riz AM, Renée Anthony T, Burns TL, Conway KM, Langlois PH, Romitti PA
Birth Defects Res 2018 Nov 15;110(19):1455-1467. Epub 2018 Oct 27 doi: 10.1002/bdr2.1386. PMID: 30367712Free PMC Article
Suhl J, Romitti PA, Rocheleau C, Cao Y, Burns TL, Conway K, Bell EM, Stewart P, Langlois P; National Birth Defects Prevention Study
J Occup Environ Hyg 2018 Sep;15(9):641-653. doi: 10.1080/15459624.2018.1484127. PMID: 29993348Free PMC Article
Chi CC, Wang SH, Kirtschig G, Wojnarowska F
J Am Acad Dermatol 2010 Apr;62(4):694-705. Epub 2010 Feb 1 doi: 10.1016/j.jaad.2009.09.041. PMID: 20117858

Prognosis

Eshete M, Alade A, Abate F, Mossey PA, Awotoye WA, Busch T, Hailu A, Demissie Y, Butali A
J Craniofac Surg 2022 Mar-Apr 01;33(2):e138-e140. doi: 10.1097/SCS.0000000000008142. PMID: 34643600Free PMC Article
Schwarz SJ, Brandenburg LS, Weingart JV, Schupp W, Füssinger MA, Pantke CF, Beck RL, Metzger MC
Laryngoscope 2021 Nov;131(11):E2764-E2769. Epub 2021 Jun 18 doi: 10.1002/lary.29602. PMID: 34142721
Choi KJ, Wlodarczyk JR, Nagengast ES, Wolfswinkel E, Munabi NCO, Yao C, Magee WP 3rd
J Craniofac Surg 2021 May 1;32(3):902-906. doi: 10.1097/SCS.0000000000007262. PMID: 33235169
Malic CC, Lam M, Donelle J, Richard L, Vigod SN, Benchimol EI
JAMA Netw Open 2020 Feb 5;3(2):e1921036. doi: 10.1001/jamanetworkopen.2019.21036. PMID: 32049294
Society for Maternal-Fetal Medicine, Benacerraf BR, Bromley B, Jelin AC
Am J Obstet Gynecol 2019 Nov;221(5):B8-B12. doi: 10.1016/j.ajog.2019.08.050. PMID: 31679595

Clinical prediction guides

Gai S, Wang L, Zheng W
BMC Med Imaging 2022 Dec 5;22(1):213. doi: 10.1186/s12880-022-00929-9. PMID: 36471263Free PMC Article
Eshete M, Alade A, Abate F, Mossey PA, Awotoye WA, Busch T, Hailu A, Demissie Y, Butali A
J Craniofac Surg 2022 Mar-Apr 01;33(2):e138-e140. doi: 10.1097/SCS.0000000000008142. PMID: 34643600Free PMC Article
Fell M, Dack K, Chummun S, Sandy J, Wren Y, Lewis S
Cleft Palate Craniofac J 2022 Sep;59(9):1185-1200. Epub 2021 Sep 27 doi: 10.1177/10556656211040015. PMID: 34569861Free PMC Article
Agnew CM, Foster Page LA, Hibbert S, Thomson WM
Cleft Palate Craniofac J 2020 Nov;57(11):1291-1297. Epub 2020 Jun 30 doi: 10.1177/1055665620936442. PMID: 32602353
Panamonta V, Pradubwong S, Panamonta M, Chowchuen B
J Med Assoc Thai 2015 Aug;98 Suppl 7:S11-21. PMID: 26742364

Recent systematic reviews

Fell M, Dack K, Chummun S, Sandy J, Wren Y, Lewis S
Cleft Palate Craniofac J 2022 Sep;59(9):1185-1200. Epub 2021 Sep 27 doi: 10.1177/10556656211040015. PMID: 34569861Free PMC Article
Worth V, Perry R, Ireland T, Wills AK, Sandy J, Ness A
Br Dent J 2017 Jul 7;223(1):37-47. doi: 10.1038/sj.bdj.2017.581. PMID: 28684841
Phan M, Conte F, Khandelwal KD, Ockeloen CW, Bartzela T, Kleefstra T, van Bokhoven H, Rubini M, Zhou H, Carels CE
Hum Genet 2016 Dec;135(12):1299-1327. Epub 2016 Oct 3 doi: 10.1007/s00439-016-1733-z. PMID: 27699475Free PMC Article
Panamonta V, Pradubwong S, Panamonta M, Chowchuen B
J Med Assoc Thai 2015 Aug;98 Suppl 7:S11-21. PMID: 26742364
Sabbagh HJ, Hassan MH, Innes NP, Elkodary HM, Little J, Mossey PA
PLoS One 2015;10(3):e0116963. Epub 2015 Mar 11 doi: 10.1371/journal.pone.0116963. PMID: 25760440Free PMC Article

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