Abnormal Development - Cleft Palate

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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.

LA42 Cleft Palate

This is the new draft ICD-11 classification, shown below on this page is the current ICD-10 information.

LA42 Cleft palate is a fissure type embryopathy that affects the soft and hard palate to varying degrees.

Introduction

Human Embryo Face (Week 7, Carnegie stage 18, 44 - 48 days, CRL 13 - 17 mm)
Fetal Palate (80 mm fetus)

International Classification of Diseases (ICD-10) - Q35 Cleft palate Incl.: fissure of palate palatoschisis Excl.: cleft palate with cleft lip (Q37.-)


Cleft palate has many different causes and in humans occurs more frequently in females (57%) than in males (43%).[1] 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.


A major contribution to the palate comes from the neural crest 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
    1. maxilla
    2. palatine bones
  2. posterior soft palate - muscular
    1. tensor veli palatini (swallowing)
    2. palatoglossus (swallowing)
    3. palatopharyngeus (breathing)
    4. levator veli palatini (swallowing)
    5. musculus uvulae (uvula movement)


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

Some Recent Findings

Cleft Palate.
Ultrasound - Cleft Lip
  • Regulation of the Epithelial Adhesion Molecule CEACAM1 Is Important for Palate Formation[2] "Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. ...These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion."
  • Role of GSK-3β in the Osteogenic Differentiation of Palatal Mesenchyme[3] "Here, we identify a critical role for GSK-3β in palatogenesis through its direct regulation of canonical Wnt signaling. These findings shed light on critical developmental pathways involved in palatogenesis and may lead to novel molecular targets to prevent cleft palate formation."
  • Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism[4] "Secondary palate fusion requires adhesion and epithelial-to-mesenchymal transition (EMT) of the epithelial layers on opposing palatal shelves. This EMT requires transforming growth factor β3 (TGFβ3), and its failure results in cleft palate. Ephrins, and their receptors, the Ephs, are responsible for migration, adhesion, and midline closure events throughout development. Ephrins can also act as signal-transducing receptors in these processes, with the Ephs serving as ligands (termed "reverse" signaling). We found that activation of ephrin reverse signaling in chicken palates induced fusion in the absence of TGFβ3, and that PI3K inhibition abrogated this effect. Further, blockage of reverse signaling inhibited TGFβ3-induced fusion in the chicken and natural fusion in the mouse. Thus, ephrin reverse signaling is necessary and sufficient to induce palate fusion independent of TGFβ3."
  • A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4[5] "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."
  • A dosage-dependent role for Spry2 in growth and patterning during palate development[6] "The formation of the palate involves the coordinated outgrowth, elevation and midline fusion of bilateral shelves leading to the separation of the oral and nasal cavities. Reciprocal signaling between adjacent fields of epithelial and mesenchymal cells directs palatal shelf growth and morphogenesis. Loss of function mutations in genes encoding FGF ligands and receptors have demonstrated a critical role for FGF signaling in mediating these epithelial-mesenchymal interactions. The Sprouty family of genes encode modulators of FGF signaling. We have established that mice carrying a deletion that removes the FGF signaling antagonist Spry2 have cleft palate."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Cleft Palate

Elisabeth Willadsen, Christina Persson, Duncan Appelbe A software program to assist coding of prelinguistic vocalizations in real time. Clin Linguist Phon: 2018;1-7 PubMed 29913085

Sreevatsan Raghavan, Koshi Philip, Puneet Batra, Agneta Marcusson Aesthetic perceptions and psychosocial impact of malocclusion: comparison between cleft and non-cleft patients and their parents. Eur J Orthod: 2018; PubMed 29912312

Patricia L Purcell, Kathleen Cy Sie, Todd C Edwards, Debra Lochner Doyle, Karin Neidt Identification of oral clefts as a risk factor for hearing loss during newborn hearing screening. J Early Hear Detect Interv: 2018, 3(1);21-28 PubMed 29911184

Moustafa Abdelaziz Moustafa, Alaa Abdelrahman Kandeel, Ahmed M A Habib, Shady A Hassan Feeding obturator as an airway adjunct during complete unilateral cleft palate repair. Indian J Anaesth: 2018, 62(5);376-380 PubMed 29910496

Huaxiang Zhao, Wenjie Zhong, Chuntao Leng, Jieni Zhang, Mengqi Zhang, Wenbin Huang, Yunfan Zhang, Weiran Li, Peizeng Jia, Jiuxiang Lin, Gulibaha Maimaitili, Feng Chen A novel PTCH1 mutation underlies non-syndromic cleft lip and/or palate in a Han Chinese family. Oral Dis: 2018; PubMed 29908092

Textbooks

Embryonic Human Cleft Palate Stage16 (ventral view)
  • 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

Face 001 icon.jpg
 ‎‎Face Development
Page | Play
Palate 001 icon.jpg
 ‎‎Palate (oral view)
Page | Play
Palate 002 icon.jpg
 ‎‎Palate (front view)
Page | Play
Tongue 001 icon.jpg
 ‎‎Tongue
Page | Play
Fetal week 10 palate icon.jpg
 ‎‎Fetal Palate
Page | Play
Links: Movies | Ultrasound


Clinical Images

Incomplete Cleft Palate

Cleft palate 001.jpg

Involving only the soft palate and uvula.[7]

Complete Cleft Palate

Cleft palate 002.jpg

Completely involving the secondary palate.[7]

Cleft palate 003.jpg

Surgical repair of the palate (palatoplasty).[7]


International Classification of Diseases - Cleft Palate

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

Veau Classification

The historic Veau System (1931)[8] classifies orofacial clefting into four classes (Veau Class I - IV) according to whether the secondary and/or primary palates are affected and by laterality.

  1. Incomplete cleft, soft palate only (no unilateral/bilateral designation)
  2. Hard and soft palate, secondary palate only (no unilateral/bilateral designation)
  3. Complete unilateral cleft including lip (primary and secondary palates)
  4. Complete bilateral cleft

Cleft Palate Genetics

An 8 month old infant with an extensive cleft palate associated with Bamforth- Lazarus syndrome.[9]
Cleft Palate Only Genes[10]
Syndrome Gene
Oculofaciocardiodental BCOR
CHARGE CHD7
Lethal and Escobar multiple pterygium CHRNG
Stickler type 1 COL2A1
Stickler type 2 COL11A1
Stickler type 3 COL11A2
Desmosterolosis DHCR24
Smith-Lemli-Opitz DHCR7
Miller DHODH
Craniofrontonasal EFNB1
Kallmann FGFR1
Crouzon FGFR2
Apert FGFR2
Otopalatodigital types 1 and 2 FLNA
Larsen syndrome; atelosteogenesis FLNB
Hereditary lymphedema-distichiasis FOXC2
Bamforth-Lazarus FOXE1
“Oro-facial-digital” GLI3
Van der Woude/popliteal pterygium IRF6
Andersen KCNJ2
Kabuki MLL2
Cornelia de Lange NIPBL
X-linked mental retardation PQBP1
Isolated cleft palate SATB2
Diastrophic dysplasia SLC26A2
Campomelic dysplasia SOX9
Pierre Robin SOX9
DiGeorge TBX1
X-linked cleft palate and ankyloglossia TBX22
Treacher Collins TCOF1
Loeys-Dietz TGFBR1
Loeys-Dietz TGFBR2
Saethre-Chotzen TWIST1

Links: OMIM Orofacial Cleft with or without cleft palate

Statistics

Cleft palate
  • International Classification of Diseases code 749.0
  • Australian national rate (1982-1992) 4.8 - 6 /10,000 births.
  • Of 1,530 infants 5.5% were stillborn and 11.5% liveborn died during neonatal period.
  • slightly more common in twin births than singleton.

(Data: Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352)

Cleft Palate - Australia (1981-1992)[11]
Australian Palate Abnormalities (2002-2003)[12]
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.
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.

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)


Cleft Risk Variants - Two genes were identified from a recent genome-wide study.[5]

  • 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.[13]

Cleft Palate Repair

Pre and post-operative palatoplasty.[7]

Surgical repair of the palate is described as palatoplasty and is often carried out between 6 to 12 months of age but also during later periods (12 to 18 months). In developing countries, this may be repaired significantly later in childhood or even go unprepared.

Surgical Repair Techniques

Some Types of Surgical Repair Techniques[14]

  • von Langenbeck's bipedicle flap technique
  • Veau-Wardill-Kilner Pushback technique
  • Bardach's two-flap technique
  • Furlow Double opposing Z-Plasty
  • Two-stage palatal repair
  • Hole in one repair
  • Raw area free palatoplasty
  • Alveolar extension palatoplasty (AEP)
  • Primary pharyngeal flap
  • Intravelar veloplasty
  • Vomer flap
  • Buccal myomucosal flap

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

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

Neural Crest

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

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.

A chicken developmental model study has identified a specific surface region, the Frontonasal Ectodermal Zone (FEZ), initially induced by bone morphogenetic proteins that appears to regulate the future growth and patterning of the frontonasal process. The specific frontonasal ectodermal zone was located in the frontonasal process ectoderm flanking a boundary between Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains.[15]

Embryonic Palate

Human primary palate

  • develops between embryonic stages 15 and 18.[16]
  • 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: Image - stage 16 | Image - stage 17 | Image - stage 18 | 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

Head Growth

  • continues postnatally - fontanelle allow head distortion on birth and early growth
  • bone plates remain unfused to allow growth, puberty growth of face

Adult

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.

Mouse palate gene expression 01.jpg

Mouse (E13.5) Palatal Shelf Wnt5a, Osr2 and Pax9 Expression.[17]

Mouse ruga pattern.jpg Mouse - Spry1 cleft palate.jpg
Mouse ruga pattern (E16) Mouse - Spry1 cleft palate

File-Cleft palate in newborn mice.jpg

Cleft palate in newborn mice.[18]


Links: Mouse Development | Bone Morphogenetic Protein | Wnt | Pax

Molecular


Links: Bone Morphogenetic Protein


References

  1. Kosowski TR, Weathers WM, Wolfswinkel EM & Ridgway EB. (2012). Cleft palate. Semin Plast Surg , 26, 164-9. PMID: 24179449 DOI.
  2. Mima J, Koshino A, Oka K, Uchida H, Hieda Y, Nohara K, Kogo M, Chai Y & Sakai T. (2013). Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation. PLoS ONE , 8, e61653. PMID: 23613893 DOI.
  3. Nelson ER, Levi B, Sorkin M, James AW, Liu KJ, Quarto N & Longaker MT. (2011). Role of GSK-3β in the osteogenic differentiation of palatal mesenchyme. PLoS ONE , 6, e25847. PMID: 22022457 DOI.
  4. San Miguel S, Serrano MJ, Sachar A, Henkemeyer M, Svoboda KK & Benson MD. (2011). Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. Dev. Dyn. , 240, 357-64. PMID: 21246652 DOI.
  5. 5.0 5.1 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.
  6. Welsh IC, Hagge-Greenberg A & O'Brien TP. (2007). A dosage-dependent role for Spry2 in growth and patterning during palate development. Mech. Dev. , 124, 746-61. PMID: 17693063 DOI.
  7. 7.0 7.1 7.2 7.3 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. Veau V. Paris: Masson & Cie; Division Palatine. (1931).
  9. Rastogi MV & LaFranchi SH. (2010). Congenital hypothyroidism. Orphanet J Rare Dis , 5, 17. PMID: 20537182 DOI.
  10. 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.
  11. P. Lancaster and E. Pedisich, Congenital Malformations Australia 1981-1992, ISSN 1321-835.
  12. 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.
  13. 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.
  14. Agrawal K. (2009). Cleft palate repair and variations. Indian J Plast Surg , 42 Suppl, S102-9. PMID: 19884664 DOI.
  15. Foppiano S, Hu D & Marcucio RS. (2007). Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development. Dev. Biol. , 312, 103-14. PMID: 18028903 DOI.
  16. 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
  17. Almaidhan A, Cesario J, Landin Malt A, Zhao Y, Sharma N, Choi V & Jeong J. (2014). Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation. BMC Dev. Biol. , 14, 3. PMID: 24433583 DOI.
  18. Jiang YH, Pan Y, Zhu L, Landa L, Yoo J, Spencer C, Lorenzo I, Brilliant M, Noebels J & Beaudet AL. (2010). Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3. PLoS ONE , 5, e12278. PMID: 20808828 DOI.
  19. Brown GD & Nazarali AJ. (2010). Matrix metalloproteinase-25 has a functional role in mouse secondary palate development and is a downstream target of TGF-β3. BMC Dev. Biol. , 10, 93. PMID: 20809987 DOI.
  20. 20.0 20.1 20.2 Kouskoura T, Kozlova A, Alexiou M, Blumer S, Zouvelou V, Katsaros C, Chiquet M, Mitsiadis TA & Graf D. (2013). The etiology of cleft palate formation in BMP7-deficient mice. PLoS ONE , 8, e59463. PMID: 23516636 DOI.


Journals

Reviews

Indian J Plast Surg. 2009 October; 42(Suppl):Cleft Lip and Palate Issue

Funato N, Nakamura M & Yanagisawa H. (2015). Molecular basis of cleft palates in mice. World J Biol Chem , 6, 121-38. PMID: 26322171 DOI.

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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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. (2018, June 19) Embryology Abnormal Development - Cleft Palate. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Cleft_Palate

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G