Abnormal Development - Cleft Lip and Palate

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LA40 Cleft lip

 ICD-11
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

Human Embryo Face (Week 7, Carnegie stage 18, 44 - 48 days, CRL 13 - 17 mm)
Human Embryo clefting. (Week 6, GA week 8, Carnegie stage 16, ventral view)
Bilateral cleft lip and cleft palate.
Ultrasound - Cleft Lip
Surgical repair of the lip (cheiloplasty).


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:

  1. maxillary components of the first pharyngeal arch (lateral)
  2. frontonasal prominence (midline)


The secondary palate can also be divided in two anatomical parts:

  1. anterior hard palate - ossified (contributions from the maxilla and palatine bones).
  2. posterior soft palate - muscular.


Palate Links: palate | cleft lip and palate | cleft palate | head | Category:Palate

Some Recent Findings

  • Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate[1] "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 (WNT9B, BMP4, 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[2]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[3] "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[4] "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."
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.

  • This search now requires a manual link as the original PubMed extension has been disabled.
  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

More? References | Discussion Page | Journal Searches | 2019 References

Search term: Cleft Lip and Palate | Cleft Lip

Older papers  
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.

  • Functional Significance of MMP3 and TIMP2 Polymorphisms in Cleft Lip/Palate[5] "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[6] "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."
Textbooks  
Pharyngeal arch cartilages.jpg
  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter Chapter 10 The Pharyngeal Apparatus pp201 - 240.
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 12 Development of the Head, the Neck, the Eyes, and the Ears pp349 - 418.

Movies

Palate Movies
Animations Ultrasound
Face 001 icon.jpg
 ‎‎Face Development
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Palate 001 icon.jpg
 ‎‎Palate (oral view)
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Palate 002 icon.jpg
 ‎‎Palate (front view)
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Cleft lip 02.jpg
 ‎‎Cleft Lip 15 Week
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Cleft lip 01.jpg
 ‎‎Cleft Lip 18 Week
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Embryo Fetus Mouse
Stage16-18 face 02.jpg
 ‎‎Face Stage 16-18
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Fetal week 10 palate icon.jpg
 ‎‎Fetal Palate
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Mouse face Bmp4 icon.jpg
 ‎‎Mouse Face Bmp4
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Mouse cranial neural crest migration 01.jpg
 ‎‎Cranial Neural Crest
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Palate Links: Palate - inferior view | MP4 movie | Palate - anterior view | MP4 movie | Palate Development | Lecture - Head Development | Lecture - GIT Development | Ultrasound | Category:Palate | Movies

Clinical Images

Uniateral Cleft Lip
Cleft lip 001.jpg Cleft lip 002.jpg
Complete Unilateral cleft lip and palate
Cleft lip 003.jpg Cleft lip 004.jpg
Complete bilateral cleft lip and palate
Cleft lip 005.jpg Cleft lip 006.jpg

Clinical image source[7]

Statistics

Cleft Palate - Australia (1981-1992)[8]

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).
  • 17% of the affected pregnancies were terminated in early pregnancy or resulted in fetal deaths. Most of the fetal deaths or terminations of pregnancy (95%) had multiple abnormalities.
  • more commonly seen in males than in females.
  • babies born before 25 weeks of gestation, 150 per 10,000 births had this anomaly. Most babies (80.0%) were born at term with a birthweight of 2,500 grams or more.
  • Maternal age group was not associated with the anomaly.
  • Rates significantly higher among Indigenous women than non Indigenous women.
Australian Palate Abnormalities (2002-2003)  
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).
  • 17% of the affected pregnancies were terminated in early pregnancy or resulted in fetal deaths. Most of the fetal deaths or terminations of pregnancy (95%) had multiple abnormalities.
  • more commonly seen in males than in females.
  • babies born before 25 weeks of gestation, 150 per 10,000 births had this anomaly. Most babies (80.0%) were born at term with a birthweight of 2,500 grams or more.
  • Maternal age group was not associated with the anomaly.
  • Rates significantly higher among Indigenous women than non Indigenous women.
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.
  • overall rate has increased to 9.1 when the rate was estimated using data from the four states that include TOP data. The reported number of fetal deaths or early terminations of pregnancy with this anomaly was small and these deaths or terminations could be due to other associated anomalies.
  • proportion of females with this anomaly was higher (56.9%) than males.
  • 52.7 per 10,000 babies born before 25 weeks of gestation.
  • 83.0% were born at term and most of the babies (82.7%) had a birthweight of 2,500 grams or more.
  • Women aged 40 years or older and women born in South Central America or the Caribbean region had the highest rates of affected births.
  • Multiple births had a significantly higher rate of affected babies than singleton births.
  • Rates did not differ significantly by Indigenous status or areas of residence.
Links: Palate Development | Head Development | Gastrointestinal Tract - Abnormalities | ICD-10 GIT | Australian Statistics
Reference: 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.

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

  1. Hypospadias (More? Male movie | Genital Abnormalities - Hypospadia)
  2. Obstructive Defects of the Renal Pelvis (More? Renal System - Abnormalities)
  3. Ventricular Septal Defect (More? Cardiovascular Abnormalities - Ventricular Septal Defect)
  4. Congenital Dislocated Hip (More? Musculoskelal Abnormalities - Congenital Dislocation of the Hip (CDH))
  5. Trisomy 21 or Down syndrome - (More? Trisomy 21)
  6. Hydrocephalus (More? Hydrocephalus)
  7. Cleft Palate (More? Palate_Development)
  8. Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued (More? (More? Trisomy 18)
  9. 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)
  10. 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

USA Abnormalities Sex Ratio (1997-2009)
Male preponderance Female preponderance
Cardiac defects
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

  • palatal shelves elevation
  • palatal shelves midline fusion
Fetal week 10 palate icon.jpg
 ‎‎Fetal Palate
Page | Play

Neural Crest

  • Mesenchyme invaded by neural crest generating connective tissue components
  • cartilage, bone, ligaments
  • arises from midbrain and hindbrain region

Face Development

Stage16-18 face animation.gif

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

  • develops between embryonic stages 15 and 18.[11]
  • fusion in the human embryo between stage 17 and 18, from an epithelial seam to the mesenchymal bridge.
Stage17-18 Primary palate.gif


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

Bailey141.jpg

Ventral aspect of hard palate of human embryo of 80 mm

Neonatal Palate

Cleft lip 007.jpg

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]
PubMed Search: Cleft palate feeder
Cleft palate feeder

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.


Links: Hearing test
Newborn hearing test.jpg

Newborn hearing test

Preterm

[15]

[16]

Links: Birth - Preterm

Animal Models

Newborn dog with cleft palate

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 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.[19]

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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. 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. 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
  8. P. Lancaster and E. Pedisich, Congenital Malformations Australia 1981-1992, ISSN 1321-835.
  9. 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.
  10. 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.
  11. 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
  12. Paradise JL & McWilliams BJ. (1974). Simplified feeder for infants with cleft palate. Pediatrics , 53, 566-8. PMID: 4823331
  13. Campbell AN & Tremouth MJ. (1987). New feeder for infants with cleft palate. Arch. Dis. Child. , 62, 1292. PMID: 3435170
  14. Chen JL, Messner AH & Curtin G. (2008). Newborn hearing screening in infants with cleft palates. Otol. Neurotol. , 29, 812-5. PMID: 18617869 DOI.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. . (). . , , . PMID: 226605140


Journals

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.

Search PubMed

Search Pubmed: cleft lip and palate development |

Additional Images

Terms

Palate Development (expand to see terms)  
  • cleft - An anatomical gap or space occuring in abnormal development in or between structures. Most commonly associated with cleft lip and cleft palate. Term is also used to describe the external groove that forms between each pharyngeal arch during their formation.
  • cleft lip - An abnormality of face development leading to an opening in the upper lip. Clefting of the lip and or palate occurs with 300+ different abnormalities. Depending on many factors, this cleft may extend further into the oral cavity leading to a cleft palate. In most cases clefting of the lip and palate can be repaired by surgery.
  • cleft palate - An abnormality of face development leading to an opening in the palate, the roof of the oral cavity between the mouth and the nose. Clefting of the lip and or palate occurs with 300+ different abnormalities. In most cases clefting of the lip and palate can be repaired by surgery. Palate formation in the embryo occurs at two distinct times and developmental processes called primary and secondary palate formation. This leads to different forms (classifications) and degrees of clefting.
  • hard palate - anterior part of the palate that becomes ossified. The posterior palate part is the soft palate.
  • epithelial mesenchymal transition - (EMT, epitheliomesenchymal transformation) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization. Process required during lip and palate developmental fusion.
  • epitheliomesenchymal transformation - (epithelial mesenchymal transition) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization.
  • incisive papilla - anterior midline palate near the incisors lying at the end of the palatine raphe.
  • levator veli palatini - Muscle forming part of the soft palate, elevates the soft palate for swallowing.
  • mastication - (chewing) Process of crushing and grinding food within the mouth.
  • maxilla - (pl. maxillae) upper jaw bone forming from the maxillary process of the first pharyngeal arch.
  • medial edge epithelial - (MEE) opposing palatal shelves adhere to each other to form this epithelial seam.
  • musculus uvulae Small muscle forming part of the soft palate lying within the uvula, shortens and broadens the uvula.
  • palatine raphe (median raphe) palate midline ridge (seam) of the mucosa, from the incisive papilla to the uvula.
  • palatal rugae - (palatine rugae, rugae) Transverse series of ridges forming on the secondary hard palate that are sequentially added during development as the palate grows. Involved in the process of mastication.
  • palatal vault - (palatine vault) Term describing the curved "arch" shape of the palate that mainly develops postnatally.
  • palate - The roof of the mouth (oral cavity) a structure which separates the oral from the nasal cavity. Develops as two lateral palatal shelves which grow and fuse in the midline. Initally a primary palate forms with fusion of the maxillary processes with the nasal processes in early face formation. Later the secondary palate forms the anterior hard palate which will ossify and separate the oral and nasal cavities. The posterior part of the palate is called the soft palate (velum, muscular palate) and contains no bone. Abnormalities of palatal shelf fusion can lead to cleft palate.
  • palatine bones - Two bones that with the maxillae form the hard palate.
  • palatogenesis - The process of palate formation, divided into primary and secondary palate development.
  • palatoglossus - (glossopalatinus, palatoglossal muscle) Small muscle forming part of the soft palate required for swallowing.
  • palatopharyngeus - (palatopharyngeal or pharyngopalatinus) Small muscle forming part of the soft palate required for breathing.
  • pharyngeal arch - (branchial arch, Greek, branchial = gill) These are a series of externally visible anterior tissue bands lying under the early brain that give rise to the structures of the head and neck. In humans, five arches form (1,2,3,4 and 6) but only four are externally visible on the embryo. Each arch has initially identical structures: an internal endodermal pouch, a mesenchymal (mesoderm and neural crest) core, a membrane (endoderm and ectoderm) and external cleft (ectoderm). Each arch mesenchymal core also contains similar components: blood vessel, nerve, muscular, cartilage. Each arch though initially formed from similar components will differentiate to form different head and neck structures.
  • philtrum - (infranasal depression, Greek, philtron = "to love" or "to kiss") Anatomically the surface midline vertical groove in the upper lip. Embryonically formed by the fusion of the frontonasal prominence (FNP) with the two maxillary processes of the first pharyngeal arch. Cleft palate (primary palate) occurs if these three regions fail to fuse during development. Fetal alcohol syndrome is also indicated by flatness and extension of this upper lip region.
  • soft palate - (velum, muscular palate) posterior part of the palate that becomes muscular. Forms 5 muscles: tensor veli palatini, palatoglossus, palatopharyngeus, levator veli palatini, musculus uvulae. The anterior palate part is the hard palate.
  • T-box 22 - (TBX22) a transcription factor that cause X-linked cleft palate and ankyloglossia in humans. Tbx22 is induced by fibroblast growth factor 8 (FGF8) in the early face while bone morphogenic protein 4 (BMP4) represses and therefore restricts its expression. (More? OMIM - TBX22)
  • tensor veli palatini - (tensor palati, tensor muscle of the velum palatinum) Small muscle forming part of the soft palate required for swallowing.
  • Transforming Growth Factor-beta - (TGFβ) factors induces both epithelial mesenchymal transition and/or apoptosis during palatal medial edge seam disintegration.
  • uvula - (Latin = a little grape) a pendulous posterior end of soft palate used to produce guttural consonants. First named in 1695.
  • Van der Woude syndrome - common syndromic cause of clefting (2% of cleft lip and palates). Van der Woude syndrome 1 1q32.2 Van der Woude syndrome 2 1p36.11
  • velopharyngeal insufficiency - (VPI) associated with cleft palate repair, describes the velum and lateral and posterior pharyngeal walls failing to separate the oral cavity from the nasal cavity during speech.
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Cite this page: Hill, M.A. (2019, June 25) 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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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G