Abnormal Development - Cleft Palate
|Embryology - 1 Dec 2021 Expand to Translate|
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[International Classification of Diseases (ICD-10) - Q35 Cleft palate Incl.: fissure of palate palatoschisis Excl.: cleft palate with cleft lip (Q37.-)
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
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
Search term: Cleft Palate
<pubmed limit=5>Cleft Palate</pubmed>
- 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.
Incomplete Cleft Palate
Involving only the soft palate and uvula.
Complete Cleft Palate
Completely involving the secondary palate.
Surgical repair of the palate (palatoplasty).
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|
Cleft Palate Genetics
|Cleft Palate Only Genes|
- 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)
|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).
|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.
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)
Cleft Risk Variants - Two genes were identified from a recent genome-wide study.
- 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
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.
- 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.
- (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)
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
- Mesenchyme invaded by neural crest generating connective tissue components
- cartilage, bone, ligaments
- arises from midbrain and hindbrain region
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.
Human primary palate
- EM Links: Image - stage 16 | Image - stage 17 | Image - stage 18 | Image - stage 19 | Palate Development
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.
- continues postnatally - fontanelle allow head distortion on birth and early growth
- bone plates remain unfused to allow growth, puberty growth of face
- 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 (E13.5) Palatal Shelf Wnt5a, Osr2 and Pax9 Expression.
|Mouse ruga pattern (E16)||Mouse - Spry1 cleft palate|
- Links: Bone Morphogenetic Protein
- <pubmed>23613893</pubmed>| PLoS One.
- <pubmed>22022457</pubmed>| PLoS One.
- <pubmed>22437671</pubmed>| PMC3928765 | J Appl Oral Sci.
- <pubmed>20537182</pubmed>| Orphanet J Rare Dis.
- P. Lancaster and E. Pedisich, Congenital Malformations Australia 1981-1992, ISSN 1321-835.
- <pubmed>24433583</pubmed>| BMC Dev Biol.
Indian J Plast Surg. 2009 October; 42(Suppl):Cleft Lip and Palate Issue <pubmed>22186724</pubmed> <pubmed>19131313</pubmed> <pubmed>16962647</pubmed> <pubmed>3074914</pubmed> <pubmed>8714286</pubmed>
<pubmed></pubmed> <pubmed></pubmed> <pubmed></pubmed> <pubmed>20149609</pubmed> <pubmed>19341725</pubmed>
- 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.
- epithelial mesenchymal transition - (EMT, epitheliomesenchymal transformation) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization.
- epitheliomesenchymal transformation - (epithelial mesenchymal transition) conversion of an epithelium into a mesenchymal (connective tissue) cellular organization.
- medial edge epithelial - (MEE) opposing palatal shelves adhere to each other to form this epithelial seam.
- 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.
- palatogenesis - The process of palate formation, divided into primary and secondary palate development.
- 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.
- 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)
- Transforming Growth Factor-beta - (TGFβ) factors induces both epithelial mesenchymal transition and/or apoptosis during palatal medial edge seam disintegration.
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- Prof Virginia Diewert - Professor of Orthodontics, University of British Columbia, who recently visited the Lab and helped with content, organisation and development of the Palate Development section.
- Medline Plus - Cleft Lip and Palate
- Better Health Channel - Cleft palate and cleft lip
- March of Dimes Birth Defects Foundation - Cleft Palate
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Cite this page: Hill, M.A. (2021, December 1) Embryology Abnormal Development - Cleft Palate. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Cleft_Palate
- © Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G