Abnormal Development - Cleft Lip and Palate: Difference between revisions
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{{Header}} | {{Header}} | ||
{{ | =LA40 Cleft lip= | ||
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! {{ICD-11}} | |||
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| {{ICD11weblink}}1481115868 Clefts of lip, alveolus or palate] - {{ICD11weblink}}172183323 '''LA40''' Cleft lip] - ''Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base.'' | |||
{{ICD11weblink}}829320510 LA40.0 Cleft lip, unilateral] | {{ICD11weblink}}574465234 LA40.2 Cleft lip, median] | |||
{{ICD11weblink}}1653169553 '''LA41''' Cleft lip and alveolus] - ''Cleft lip and alveolus is a fissure type embryopathy that involves the upper lip, nasal base and alveolar ridge in variable degrees.'' | |||
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== Introduction == | == Introduction == | ||
[[File:Stage18 em11.jpg|thumb|200px|Human Embryo Face ([[Week 7]], | [[File:Stage18 em11.jpg|thumb|200px|Human Embryo Face ([[Week 7]], Carnegie stage {{CS18}}, 44 - 48 days, CRL 13 - 17 mm)]] | ||
[[File:Stage16_cleft_palate.jpg|thumb|200px|Human Embryo clefting. (Week 6, {{GA}} week 8, | [[File:Stage16_cleft_palate.jpg|thumb|200px|Human Embryo clefting. (Week 6, {{GA}} week 8, Carnegie stage {{CS16}}, ventral view)]] | ||
[[File:Bilateral_cleft_palate.jpg|thumb|200px|Bilateral cleft palate]] | [[File:Bilateral_cleft_palate.jpg|thumb|200px|Bilateral cleft lip and cleft palate.]] | ||
[[File:Cleft_lip_01.jpg|thumb|200px|link=Ultrasound - Cleft Lip Movie 1|Ultrasound - Cleft Lip]] | [[File:Cleft_lip_01.jpg|thumb|200px|link=Ultrasound - Cleft Lip Movie 1|Ultrasound - Cleft Lip]] | ||
[[File:Cleft lip 007.jpg|thumb|200px|Surgical repair of the lip (cheiloplasty).]] | |||
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* ''' | * '''Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate'''{{#pmid:31063268|PMID31063268}} "Cleft lip with/without cleft palate (CLP) is a common craniofacial malformation with complex etiologies, reflecting both genetic and environmental factors. Most of the suspected genetic risk for CLP has yet to be identified. To further classify risk loci and estimate the contribution of rare variants, we sequenced the exons in 49 candidate genes in 323 CLP cases and 211 nonmalformed controls. Our findings indicated that rare, protein-altering variants displayed markedly higher burdens in CLP cases at relevant loci. First, putative loss-of-function mutations (nonsense, frameshift) were significantly enriched among cases: 13 of 323 cases (~4%) harbored such alleles within these 49 genes, versus one such change in controls (p = 0.01). Second, in gene-level analyses, the burden of rare alleles showed greater case-association for several genes previously implicated in cleft risk. For example, BHMT displayed a 10-fold increase in protein-altering variants in CLP cases (p = .03), including multiple case occurrences of a rare frameshift mutation (K400 fs). Other loci with greater rare, coding allele burdens in cases were in signaling pathways relevant to craniofacial development ({{WNT}}9B, {{BMP}}4, BMPR1B) as well as the methionine cycle (MTRR). We conclude that rare coding variants may confer risk for isolated CLP." | ||
* ''' | |||
* '''Epidemiology and clinical profile of individuals with cleft lip and palate utilising specialised academic treatment centres in South Africa'''{{#pmid:31071123|PMID31071123}}The study was conducted to determine the epidemiology and clinical profile of individuals with cleft lip and/or palate (CLP) utilizing specialized academic treatment centres in South Africa's public health sector. The Human Research Ethics Committee of the University of the Witwatersrand in Johannesburg provided ethical approval for the study. We analysed 699 records of individuals with CLP. The estimated prevalence of CLP in the South African public health sector was 0.3 per 1000 live births, with provincial variation of 0.1/1000 to 1.2/1000. The distribution of clefts was: 35.3% cleft palate; 34.6% cleft lip and palate; 19.0% cleft lip and other cleft anomalies at 2%. Of the total number of CLP, 47.5% were male and 52.5% female, and this difference was statistically significant (p<0.001). The majority of clefts occurred on the left for males (35.5%) and palate for females (43.4%), with a male predominance of unilateral cleft lip and palate (53.3%)." | |||
* '''Knockdown of Crispld2 in zebrafish identifies a novel network for nonsyndromic cleft lip with or without cleft palate candidate genes'''{{#pmid:29899370|PMID29899370}} "Orofacial development is a multifaceted process involving tightly regulated genetic signaling networks, that when perturbed, lead to orofacial abnormalities including cleft lip and/or cleft palate. We and others have shown an association between the cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) gene and nonsyndromic cleft lip with or without cleft palate (NSCLP). Further, we demonstrated that knockdown of Crispld2 in zebrafish alters neural crest cell migration patterns resulting in abnormal jaw and palate development. In this study, we performed RNA profiling in zebrafish embryos and identified 249 differentially expressed genes following knockdown of Crispld2. In silico pathway analysis identified a network of seven genes previously implicated in orofacial development for which differential expression was validated in three of the seven genes (CASP8, FOS, and MMP2)." | |||
* '''Classification of Cleft Lip/Palate: Then and Now'''{{#pmid:26339868|PMID26339868}} "Cleft lip and/or palate (CL/P) is phenotypically diverse, making classification difficult. This article explores the evolution of ideas regarding CL/P classification and includes the schemes described by Davis and Ritchie (1922), Brophy (1923), Veau (1931), Fogh-Andersen (1943), Kernahan and Stark (1958), Harkins et al. (1962), Broadbent et al. (1968), Spina (1973), and others. Based on these systems, a longhand structured form is proposed for describing CL/P in a way that is clear, comprehensive, and consistent. A complementary shorthand notation is also described to improve the utility and convenience of this structured form." | |||
|} | |} | ||
{| class="wikitable mw-collapsible mw-collapsed" | |||
{| class="wikitable collapsible collapsed" | ! More recent papers | ||
! More recent papers | |||
|- | |- | ||
| [[File:Mark_Hill.jpg|90px|left]] {{Most_Recent_Refs}} | | [[File:Mark_Hill.jpg|90px|left]] {{Most_Recent_Refs}} | ||
Search term: ''Cleft Lip and Palate'' | Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Cleft+Lip+and+Palate ''Cleft Lip and Palate''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Cleft+Lip ''Cleft Lip''] | ||
|} | |||
{| class="wikitable mw-collapsible mw-collapsed" | |||
! Older papers | |||
|- | |||
| {{Older papers}} | |||
* '''Functional Significance of MMP3 and TIMP2 Polymorphisms in Cleft Lip/Palate'''{{#pmid:24799419|PMID24799419}} "Evidence from biological and human studies strongly supports a role for MMP and TIMP genes as candidate genes for non-syndromic cleft lip with or without cleft palate (NSCL/P). We previously showed the association of promoter polymorphisms in MMP3 (rs3025058 and rs522616) and TIMP2 (rs8179096) with NSCL/P. In this study, we examined the functional significance of these polymorphisms. A specific DNA-protein complex for MMP3 rs522616 A was detected, and this allele by itself showed greater promoter activity than the G allele. However, the effect of rs522616 was ultimately regulated by the rs3025058 allele on the background. For TIMP2 rs8179096, the T allele showed a 2.5-fold increase in promoter activity when compared with allele C, whereas both C and T alleles were found to bind to nuclear factor kappa B. Our results provide new evidence that promoter polymorphisms in MMP3 and TIMP2 are functional and may affect gene transcription with possible effects on craniofacial development." | |||
* '''A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4'''{{#pmid:20436469|PMID20436469}} "Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 x 10(-12)) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance." | |||
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==Movies== | ==Movies== | ||
{{Palate Movies}} | |||
==Clinical Images== | ==Clinical Images== | ||
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! Uniateral Cleft Lip | ! Uniateral Cleft Lip | ||
|- | |- | ||
| [[File:Cleft_lip_001.jpg]] [[ | | [[File:Cleft_lip_001.jpg|300px]] [[File:Cleft_lip_002.jpg|300px]] | ||
|- | |- | ||
! Complete Unilateral cleft lip and palate | ! Complete Unilateral cleft lip and palate | ||
|- | |- | ||
| [[File: | | [[File:Cleft_lip_003.jpg|300px]] [[File:Cleft_lip_004.jpg|300px]] | ||
|- | |- | ||
! Complete bilateral cleft lip and palate | ! Complete bilateral cleft lip and palate | ||
|- | |- | ||
| [[ | | [[File:Cleft_lip_005.jpg|300px]] [[File:Cleft_lip_006.jpg|300px]] | ||
|} | |} | ||
Clinical image source{{#pmid:22437671|PMID22437671}} | |||
==Statistics== | ==Statistics== | ||
[[File:Australian abnormalities 81-92 git.jpg|thumb|350px|Cleft Palate - Australia (1981-1992)<ref>P. Lancaster and E. Pedisich, '''Congenital Malformations Australia''' 1981-1992, ISSN 1321-835.</ref>]] | [[File:Australian abnormalities 81-92 git.jpg|thumb|350px|Cleft Palate - Australia (1981-1992)<ref>P. Lancaster and E. Pedisich, '''Congenital Malformations Australia''' 1981-1992, ISSN 1321-835.</ref>]] | ||
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{{10Victorian Anomalies03-04}} | {{10Victorian Anomalies03-04}} | ||
===USA=== | |||
{{USA 1997-2009 Abnormalities Sex Ratio table}} | |||
== Development Overview == | == Development Overview == | ||
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Human primary palate | Human primary palate | ||
* develops between embryonic stages | * develops between embryonic stages {{CS15}} and {{CS18}}.{{#pmid:8227288|PMID8227288}} | ||
* fusion in the human embryo between stage | * fusion in the human embryo between stage {{CS17}} and {{CS18}}, from an epithelial seam to the mesenchymal bridge. | ||
| [[File:Stage17-18 Primary palate.gif]] | | [[File:Stage17-18 Primary palate.gif]] | ||
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:'''EM Links:''' [[:File:Stage16 em01.jpg|Image - stage | :'''EM Links:''' [[:File:Stage16 em01.jpg|Image - stage {{CS16}}]] | [[:File:Stage17 em01.jpg|Image - stage {{CS17}}]] | [[:File:Stage18 em01.jpg|Image - stage {{CS18}}]] | [[:File:Stage19 em01.jpg|Image - stage {{CS19}}]] | [[Palate Development]] | ||
==Fetal Palate== | ==Fetal Palate== | ||
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Ventral aspect of hard palate of human embryo of 80 mm | Ventral aspect of hard palate of human embryo of 80 mm | ||
==Neonatal Palate== | |||
[[File:Cleft lip 007.jpg|400px]] | |||
Surgical repair of the lip (cheiloplasty).{{#pmid:22437671|PMID22437671}} | |||
===Feeding=== | |||
{| | |||
| Both cleft lip and palate provide issues related to both feeding and nutrition before a surgical repair can be carried out.{{#pmid:4823331|PMID4823331}}{{#pmid:3435170|PMID3435170}} | |||
:'''PubMed Search:''' [https://www.ncbi.nlm.nih.gov/pubmed/?term=Cleft+palate+feeder Cleft palate feeder] | |||
| [[File:Cleft palate feeder.jpg|150px|alt=Cleft palate feeder]] | |||
Cleft palate feeder | |||
|} | |||
===Hearing=== | |||
{| | |||
| Note also the neonatal association with conductive hearing loss from serous effusion with cleft lip and palate.{{#pmid:18617869|PMID18617869}} Tympanostomy tubes can help with some but not all these neonates. | |||
:'''Links:''' [[Hearing test]] | |||
| [[File:Newborn hearing test.jpg|150px]] | |||
Newborn hearing test | |||
|} | |||
===Preterm=== | |||
{{#pmid:17666126|PMID17666126}} | |||
{{#pmid:16460577|PMID16460577}} | |||
:'''Links:''' [[Birth - Preterm]] | |||
==Animal Models== | ==Animal Models== | ||
[[File:Dog day0-cleft palate.jpg|thumb|Newborn dog with cleft palate]] | [[File:Dog day0-cleft palate.jpg|thumb|Newborn dog with cleft palate]] | ||
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:'''Links:''' [[Mouse Development]] | [[Developmental_Signals_-_Bone_Morphogenetic_Protein|Bone Morphogenetic Protein]] | [[Developmental Signals - Wnt|Wnt]] | [[Developmental_Signals_-_Pax|Pax]] | :'''Links:''' [[Mouse Development]] | [[Developmental_Signals_-_Bone_Morphogenetic_Protein|Bone Morphogenetic Protein]] | [[Developmental Signals - Wnt|Wnt]] | [[Developmental_Signals_-_Pax|Pax]] | ||
==International Classification of Diseases | ==International Classification of Diseases== | ||
Cleft lip and cleft palate (Q35-Q37) | Cleft lip and cleft palate (Q35-Q37) | ||
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{| class="wikitable collapsible collapsed" | {| class="wikitable collapsible collapsed" | ||
! Cleft Lip Genes | ! Cleft Lip Genes{{#pmid:21331089|PMID21331089}} | ||
|- | |- | ||
| '''Midline Cleft Lip Genes''' | | '''Midline Cleft Lip Genes''' | ||
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==Cleft Risk Variants== | ==Cleft Risk Variants== | ||
Two genes were identified from a recent genome-wide study. | Two genes were identified from a recent genome-wide study.{{#pmid:20436469|PMID20436469}} | ||
* '''MAFB''' is expressed in the mouse palatal shelf. | * '''MAFB''' is expressed in the mouse palatal shelf. | ||
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===Folate=== | ===Folate=== | ||
A recent study of periconceptional folate supplementation using the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010) identified no statistically significant evidence of any effects on prevention of cleft palate and cleft lip at birth. | A recent study of periconceptional folate supplementation using the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010) identified no statistically significant evidence of any effects on prevention of cleft palate and cleft lip at birth.{{#pmid:20927767|PMID20927767}} | ||
==Molecular== | |||
[http://www.omim.org/entry/608148 SATB2] - Special At-Rich Sequence-Binding Protein has a role in craniofacial development and patterning.{{#pmid:226605140|PMID226605140}} | |||
[http://www.omim.org/entry/603273?search=p63&highlight=p63 P63] - cleft palate is a form of ectodermal dysplasia and functioning p63 prevents dysplasia. | |||
[http://www.omim.org/entry/300307 TBX22] - has been identified as expressed in the palatal shelves during the elevation process. | |||
[http://www.omim.org/entry/600742 TGFBR3] - Transforming Growth Factor-Beta Receptor Type III loss of signaling by receptor loss was found to be associated with cleft palate formation due to aberrant cell cycle progression and altered gene expression. | |||
== References == | == References == | ||
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===Reviews=== | ===Reviews=== | ||
Indian J Plast Surg. 2009 October; 42(Suppl):[http://www.ncbi.nlm.nih.gov/pmc/issues/185089 Cleft Lip and Palate Issue] | Indian J Plast Surg. 2009 October; 42(Suppl):[http://www.ncbi.nlm.nih.gov/pmc/issues/185089 Cleft Lip and Palate Issue] | ||
{{#pmid:22186724}} | |||
{{#pmid:19131313}} | |||
{{#pmid:16962647}} | |||
{{#pmid:3074914}} | |||
{{#pmid:8714286}} | |||
===Articles=== | ===Articles=== | ||
{{#pmid:20149609}} | |||
{{#pmid:19341725}} | |||
===Search PubMed=== | ===Search PubMed=== | ||
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<gallery> | <gallery> | ||
File:Unilateral_cleft_palate.jpg|Unilateral cleft lip and palate | File:Unilateral_cleft_palate.jpg|Unilateral cleft lip and palate | ||
</gallery> | </gallery> | ||
==Terms== | ==Terms== | ||
{{Palate terms}} | |||
==External Links== | ==External Links== | ||
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* '''Better Health Channel''' - [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Cleft_palate_and_cleft_lip Cleft palate and cleft lip] | * '''Better Health Channel''' - [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Cleft_palate_and_cleft_lip Cleft palate and cleft lip] | ||
* '''March of Dimes Birth Defects Foundation''' - [http://www.marchofdimes.com/baby/birthdefects_cleftpalate.html Cleft Palate] | * '''March of Dimes Birth Defects Foundation''' - [http://www.marchofdimes.com/baby/birthdefects_cleftpalate.html Cleft Palate] | ||
* Victoria [http://www.health.vic.gov.au/neonatalhandbook/congenital/cleft-lip-and-palate.htm Neonatal ehandbook - Cleft Lip and Palate] | [http://www.rch.org.au/kidsinfo/fact_sheets/Cleft_Lip_and_Palate_an_overview Royal Children's Hospital Melbourne] | |||
Latest revision as of 22:44, 12 May 2019
Embryology - 10 Jun 2024 Expand to Translate |
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LA40 Cleft lip
ICD-11 |
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Clefts of lip, alveolus or palate - LA40 Cleft lip - Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base.
LA40.0 Cleft lip, unilateral | LA40.2 Cleft lip, median LA41 Cleft lip and alveolus - Cleft lip and alveolus is a fissure type embryopathy that involves the upper lip, nasal base and alveolar ridge in variable degrees. |
Introduction
The way in which the upper jaw (maxillae) forms from fusion of the smaller upper prominence of the first pharyngeal arch leads to a common congenital defect in this region called "clefting", which may involve either the upper lip, the palate or both structures.
The palate anatomically separates the nasal cavity from the oral cavity and structurally has a bony (hard) anterior component and a muscular (soft) posterior component ending with the uvula. The oral side of the palate is covered with a squamous stratified (pluristratified) epithelium. The surface of the hard palate of most mammalian species is further thrown into a series of transversal palatal ridges or rugae palatinae. Both the palatal ridge number and arrangement are also species specific.
Neural crest has a major contribution to the palate development and there are a number of molecular, mechanical and morphological steps in involving the fusion of contributing structures including a key epithelial to mesenchymal transition. In palate formation there are two main and separate times and events of development, during embryonic (primary palate) and an early fetal (secondary palate). This separation of events into embryonic and fetal period corresponds closely to the classification of associated palate abnormalities.
The primary palate is formed by two parts:
- maxillary components of the first pharyngeal arch (lateral)
- frontonasal prominence (midline)
The secondary palate can also be divided in two anatomical parts:
- anterior hard palate - ossified (contributions from the maxilla and palatine bones).
- posterior soft palate - muscular.
Palate Links: palate | cleft lip and palate | cleft palate | head | Category:Palate |
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Cleft Lip and Palate | Cleft Lip |
Older papers |
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These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
See also the Discussion Page for other references listed by year and References on this current page.
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Clinical Images
Uniateral Cleft Lip |
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Complete Unilateral cleft lip and palate |
Complete bilateral cleft lip and palate |
Clinical image source[7]
Statistics
Australia
Australian Palate Abnormalities (2002-2003)[9]
Cleft lip with or without cleft palate (9.2 per 10,000 births) ICD-10 Q36.0, Q36.1, Q36.9, Q37.0–Q37.5, Q37.8, Q37.9 |
A congenital anomaly characterised by a partial or complete clefting of the upper lip, with or without clefting of the alveolar ridge or the hard palate. Excludes a midline cleft of the upper or lower lip and an oblique facial fissure (going towards the eye).
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Australian Palate Abnormalities (2002-2003) |
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Cleft lip with or without cleft palate (9.2 per 10,000 births) ICD-10 Q36.0, Q36.1, Q36.9, Q37.0–Q37.5, Q37.8, Q37.9 |
A congenital anomaly characterised by a partial or complete clefting of the upper lip, with or without clefting of the alveolar ridge or the hard palate. Excludes a midline cleft of the upper or lower lip and an oblique facial fissure (going towards the eye).
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Cleft palate without cleft lip (8.1 per 10,000 births) ICD-10 Q35.0–Q35.9 |
A congenital anomaly characterised by a closure defect of the hard and/or soft palate behind the foramen incisivum without a cleft lip. This anomaly includes sub-mucous cleft palate, but excludes cleft palate with a cleft lip, a functional short palate and high narrow palate.
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Victorian Perinatal Data Collection Unit (2003-2004) Top 10 abnormalities, cleft lip and palate was number 10 on the list and the condition occurred with another defect in 33.7% of cases.
Ten most frequently reported Birth Anomalies
- Hypospadias (More? Male movie | Genital Abnormalities - Hypospadia)
- Obstructive Defects of the Renal Pelvis (More? Renal System - Abnormalities)
- Ventricular Septal Defect (More? Cardiovascular Abnormalities - Ventricular Septal Defect)
- Congenital Dislocated Hip (More? Musculoskelal Abnormalities - Congenital Dislocation of the Hip (CDH))
- Trisomy 21 or Down syndrome - (More? Trisomy 21)
- Hydrocephalus (More? Hydrocephalus)
- Cleft Palate (More? Palate_Development)
- Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued (More? (More? Trisomy 18)
- Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%). (More? Renal System - Abnormalities)
- Cleft Lip and Palate - occur with another defect in 33.7% of cases.(More? Palate Development | Head Development)
(From the Victorian Perinatal Data Collection Unit in the Australian state of Victoria between 2003-2004)
USA
Male preponderance | Female preponderance |
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Cardiac defects | |
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Table data[10] Links: abnormal development | cardiovascular abnormalities | USA | Male | Female | cleft lip and palate |
Development Overview
- week 4 - pharyngeal arch formation, first pharngeal arch contributes mandible and maxilla.
- week 6 - 7 - primary palate formation maxillary processes and frontonasal prominence.
- week 9 - secondary palate shelves fuse, separating oral and nasal cavities.
Embryonic Period
- (week 4) - pharyngeal arch formation in rostrocaudal sequence (1, 2, 3, 4 and 6)
- First pharyngeal arch - upper maxillary (pair) and lower mandibular prominences
- Late embryonic period - maxillary prominences fuse with frontonasal prominence forming upper jaw (maxilla and upper lip)
Fetal Period
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Neural Crest
- Mesenchyme invaded by neural crest generating connective tissue components
- cartilage, bone, ligaments
- arises from midbrain and hindbrain region
Face Development
Begins week 4 centered around stomodeum, external depression at oral membrane
5 initial primordia from neural crest mesenchyme
- single frontonasal prominence (FNP) - forms forehead, nose dorsum and apex
- nasal placodes develop later bilateral, pushed medially
- paired maxillary prominences - form upper cheek and upper lip
- paired mandibular prominences - lower cheek, chin and lower lip
Frontonasal Process
The frontonasal process (FNP) forms the majority of the superior part of the early face primordia. It later fuses with the maxillary component of the first pharyngeal arch to form the upper jaw. Failure of this fusion event during the embryonic period leads to cleft lip. Under the surface ectoderm the process mesenchyme consists of two cell populations; neural crest cells, forming the connective tissues; and the mesoderm forming the endothelium of the vascular network.
Embryonic Palate
Human primary palate |
- EM Links: [[:File:Stage16 em01.jpg|Image - stage 16]] | [[:File:Stage17 em01.jpg|Image - stage 17]] | [[:File:Stage18 em01.jpg|Image - stage 18]] | [[:File:Stage19 em01.jpg|Image - stage 19]] | Palate Development
Fetal Palate
Secondary palate, fusion in the human embryo in week 9. This requires the early palatal shelves growth, elevation, and fusion. There are many fusion events occurring during this period between each palatal shelf, to the primary palate, and also to the nasal septum.
palatal shelf elevation | secondary palate
Ventral aspect of hard palate of human embryo of 80 mm
Neonatal Palate
Surgical repair of the lip (cheiloplasty).[7]
Feeding
Both cleft lip and palate provide issues related to both feeding and nutrition before a surgical repair can be carried out.[12][13]
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Cleft palate feeder |
Hearing
Note also the neonatal association with conductive hearing loss from serous effusion with cleft lip and palate.[14] Tympanostomy tubes can help with some but not all these neonates.
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Newborn hearing test |
Preterm
- Links: Birth - Preterm
Animal Models
Mouse Palate
- E11 - protrude from bilateral maxillary processes
- E12.5 - secondary palatal development begins
- E12.5-E14 - grow vertically along the developing tongue
- E14.5 - they elevate, meet, and fuse at the midline, to form an intact palate shelf, reflex opening and closing movements of the mouth
- E15.5 - palatal fusion is complete, mesenchymal condensation followed by osteogenic differentiation occurs.
- Links: Mouse Development | Bone Morphogenetic Protein | Wnt | Pax
International Classification of Diseases
Cleft lip and cleft palate (Q35-Q37)
Use additional code (Q30.2), if desired, to identify associated malformations of the nose. Excludes Robin's syndrome ( Q87.0 )
Q37 | Cleft palate with cleft lip |
Q37.0 | Cleft hard palate with bilateral cleft lip |
Q37.1 | Cleft hard palate with unilateral cleft lip |
Cleft hard palate with cleft lip NOS | |
Q37.2 | Cleft soft palate with bilateral cleft lip |
Q37.3 | Cleft soft palate with unilateral cleft lip |
Cleft soft palate with cleft lip NOS | |
Q37.4 | Cleft hard and soft palate with bilateral cleft lip |
Q37.5 | Cleft hard and soft palate with unilateral cleft lip |
Cleft hard and soft palate with cleft lip NOS | |
Q37.8 | Unspecified cleft palate with bilateral cleft lip |
Q37.9 | Unspecified cleft palate with unilateral cleft lip |
Cleft palate with cleft lip NOS |
Cleft Lip
Cleft Lip Genes[17] | ||||||||||||||||||||||||||||||||||||||
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Midline Cleft Lip Genes
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Cleft Lip (+/− cleft palate) Genes
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Cleft Risk Variants
Two genes were identified from a recent genome-wide study.[6]
- MAFB is expressed in the mouse palatal shelf.
- ABCA4 is a member of a superfamily of transmembrane proteins, and mutations in ABCA4 play a major role in the etiology of Stargardt disease and related retinopathies. Gene produces an ATP-binding cassette (ABC) superfamily trans-membrane protein
- Links: OMIM - MAFB | OMIM - ABCA4
Folate
A recent study of periconceptional folate supplementation using the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010) identified no statistically significant evidence of any effects on prevention of cleft palate and cleft lip at birth.[18]
Molecular
SATB2 - Special At-Rich Sequence-Binding Protein has a role in craniofacial development and patterning.PubmedParser error: The PubmedParser extension received invalid XML data. ()
P63 - cleft palate is a form of ectodermal dysplasia and functioning p63 prevents dysplasia.
TBX22 - has been identified as expressed in the palatal shelves during the elevation process.
TGFBR3 - Transforming Growth Factor-Beta Receptor Type III loss of signaling by receptor loss was found to be associated with cleft palate formation due to aberrant cell cycle progression and altered gene expression.
References
- ↑ Marini NJ, Asrani K, Yang W, Rine J & Shaw GM. (2019). Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate. Am. J. Med. Genet. A , , . PMID: 31063268 DOI.
- ↑ Hlongwa P, Levin J & Rispel LC. (2019). Epidemiology and clinical profile of individuals with cleft lip and palate utilising specialised academic treatment centres in South Africa. PLoS ONE , 14, e0215931. PMID: 31071123 DOI.
- ↑ Chiquet BT, Yuan Q, Swindell EC, Maili L, Plant R, Dyke J, Boyer R, Teichgraeber JF, Greives MR, Mulliken JB, Letra A, Blanton SH & Hecht JT. (2018). Knockdown of Crispld2 in zebrafish identifies a novel network for nonsyndromic cleft lip with or without cleft palate candidate genes. Eur. J. Hum. Genet. , , . PMID: 29899370 DOI.
- ↑ Allori AC, Mulliken JB, Meara JG, Shusterman S & Marcus JR. (2017). Classification of Cleft Lip/Palate: Then and Now. Cleft Palate Craniofac. J. , 54, 175-188. PMID: 26339868 DOI.
- ↑ Letra A, Zhao M, Silva RM, Vieira AR & Hecht JT. (2014). Functional Significance of MMP3 and TIMP2 Polymorphisms in Cleft Lip/Palate. J. Dent. Res. , 93, 651-6. PMID: 24799419 DOI.
- ↑ 6.0 6.1 Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, Liang KY, Wu T, Murray T, Fallin MD, Redett RA, Raymond G, Schwender H, Jin SC, Cooper ME, Dunnwald M, Mansilla MA, Leslie E, Bullard S, Lidral AC, Moreno LM, Menezes R, Vieira AR, Petrin A, Wilcox AJ, Lie RT, Jabs EW, Wu-Chou YH, Chen PK, Wang H, Ye X, Huang S, Yeow V, Chong SS, Jee SH, Shi B, Christensen K, Melbye M, Doheny KF, Pugh EW, Ling H, Castilla EE, Czeizel AE, Ma L, Field LL, Brody L, Pangilinan F, Mills JL, Molloy AM, Kirke PN, Scott JM, Scott JM, Arcos-Burgos M & Scott AF. (2010). A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat. Genet. , 42, 525-9. PMID: 20436469 DOI.
- ↑ 7.0 7.1 Freitas JA, das Neves LT, de Almeida AL, Garib DG, Trindade-Suedam IK, Yaedú RY, Lauris Rde C, Soares S, Oliveira TM & Pinto JH. (2012). Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP)--Part 1: overall aspects. J Appl Oral Sci , 20, 9-15. PMID: 22437671
- ↑ P. Lancaster and E. Pedisich, Congenital Malformations Australia 1981-1992, ISSN 1321-835.
- ↑ Abeywardana S & Sullivan EA 2008. Congenital Anomalies in Australia 2002-2003. Birth anomalies series no. 3 Cat. no. PER 41. Sydney: AIHW National Perinatal Statistics Unit.
- ↑ Michalski AM, Richardson SD, Browne ML, Carmichael SL, Canfield MA, VanZutphen AR, Anderka MT, Marshall EG & Druschel CM. (2015). Sex ratios among infants with birth defects, National Birth Defects Prevention Study, 1997-2009. Am. J. Med. Genet. A , 167A, 1071-81. PMID: 25711982 DOI.
- ↑ Diewert VM & Lozanoff S. (1993). A morphometric analysis of human embryonic craniofacial growth in the median plane during primary palate formation. J. Craniofac. Genet. Dev. Biol. , 13, 147-61. PMID: 8227288
- ↑ Paradise JL & McWilliams BJ. (1974). Simplified feeder for infants with cleft palate. Pediatrics , 53, 566-8. PMID: 4823331
- ↑ Campbell AN & Tremouth MJ. (1987). New feeder for infants with cleft palate. Arch. Dis. Child. , 62, 1292. PMID: 3435170
- ↑ Chen JL, Messner AH & Curtin G. (2008). Newborn hearing screening in infants with cleft palates. Otol. Neurotol. , 29, 812-5. PMID: 18617869 DOI.
- ↑ Eifinger F, Lang-Roth R, Braumann B, Saffar M, Huenseler C & Kribs A. (2008). Primary respiratory support in preterm infants with cleft lip and palate. J Laryngol Otol , 122, 307-9. PMID: 17666126 DOI.
- ↑ McMahon RM, Bagchi I, Worsey S & Kumararatne B. (2006). Use of mask continuous positive airway pressure in a preterm infant presenting with bilateral cleft lip and palate. J Laryngol Otol , 120, 228-9. PMID: 16460577 DOI.
- ↑ Dixon MJ, Marazita ML, Beaty TH & Murray JC. (2011). Cleft lip and palate: understanding genetic and environmental influences. Nat. Rev. Genet. , 12, 167-78. PMID: 21331089 DOI.
- ↑ De-Regil LM, Fernández-Gaxiola AC, Dowswell T & Peña-Rosas JP. (2010). Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev , , CD007950. PMID: 20927767 DOI.
Journals
- The Cleft Palate-Craniofacial Journal Homepage | Available issues
Reviews
Indian J Plast Surg. 2009 October; 42(Suppl):Cleft Lip and Palate Issue Bush JO & Jiang R. (2012). Palatogenesis: morphogenetic and molecular mechanisms of secondary palate development. Development , 139, 231-43. PMID: 22186724 DOI.
Meng L, Bian Z, Torensma R & Von den Hoff JW. (2009). Biological mechanisms in palatogenesis and cleft palate. J. Dent. Res. , 88, 22-33. PMID: 19131313 DOI.
Dudas M, Li WY, Kim J, Yang A & Kaartinen V. (2007). Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect. Acta Histochem. , 109, 1-14. PMID: 16962647 DOI.
Ferguson MW. (1988). Palate development. Development , 103 Suppl, 41-60. PMID: 3074914
Hay ED. (1995). An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) , 154, 8-20. PMID: 8714286
Articles
Steding G & Jian Y. (2010). The origin and early development of the nasal septum in human embryos. Ann. Anat. , 192, 82-5. PMID: 20149609 DOI.
Xiong W, He F, Morikawa Y, Yu X, Zhang Z, Lan Y, Jiang R, Cserjesi P & Chen Y. (2009). Hand2 is required in the epithelium for palatogenesis in mice. Dev. Biol. , 330, 131-41. PMID: 19341725 DOI.
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Cite this page: Hill, M.A. (2024, June 10) Embryology Abnormal Development - Cleft Lip and Palate. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Cleft_Lip_and_Palate
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