Cleft lip and cleft palate
also known as orofacial cleft, is a group of conditions that includes cleft lip (CL), cleft palate (CP), and both together (CLP). A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the roof of the mouth contains an opening into the nose. These disorders can result in feeding problems, speech problems, hearing problems, and frequent ear infections. Less than half the time the condition is associated with other disorders.
Cleft lip and palate are the result of tissues of the face not joining properly during development. As such, they are a type of birth defect. The cause is unknown in most cases. Risk factors include smoking during pregnancy, diabetes, obesity, an older mother, and certain medications (such as some used to treat seizures). Cleft lip and cleft palate can often be diagnosed during pregnancy with an ultrasound exam.
A cleft lip or palate can be successfully treated with surgery. This is often done in the first few months of life for cleft lip and before eighteen months for cleft palate. Speech therapy and dental care may also be needed. With appropriate treatment, outcomes are good.
Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world. CL is about twice as common in males as females, while CP without CL is more common in females. In 2017, it resulted in about 3,800 deaths globally, down from 14,600 deaths in 1990. The condition was formerly known as a "hare-lip" because of its resemblance to a hare or rabbit, but that term is now generally considered to be offensive.
Signs and symptoms
Cleft lipIf the cleft does not affect the palate structure of the mouth, it is referred to as cleft lip. Cleft lip is formed in the top of the lip as either a small gap or an indentation in the lip (partial or incomplete cleft), or it continues into the nose (complete cleft). Lip cleft can occur as a one-sided (unilateral) or two-sided (bilateral) condition. It is due to the failure of fusion of the maxillary prominence and medial nasal processes (formation of the primary palate).
A mild form of a cleft lip is a microform cleft. A microform cleft can appear as small as a little dent in the red part of the lip or look like a scar from the lip up to the nostril. In some cases muscle tissue in the lip underneath the scar is affected and might require reconstructive surgery. It is advised to have newborn infants with a microform cleft checked with a craniofacial team as soon as possible to determine the severity of the cleft.
Cleft palate
Cleft palate is a condition in which the two plates of the skull that form the hard palate (roof of the mouth) are not completely joined. The soft palate is in these cases cleft as well. In most cases, cleft lip is also present.
Palate cleft can occur as complete (soft and hard palate, possibly including a gap in the jaw) or incomplete (a 'hole' in the roof of the mouth, usually as a cleft soft palate). When cleft palate occurs, the uvula is usually split. It occurs due to the failure of fusion of the lateral palatine processes, the nasal septum, or the median palatine processes (formation of the secondary palate).
The hole in the roof of the mouth caused by a cleft connects the mouth directly to the inside of the nose.
Note: the next images show the roof of the mouth. The top shows the nose, the lips are colored pink. For clarity the images depict a toothless infant.
A result of an open connection between the mouth and inside the nose is called velopharyngeal inadequacy (VPI). Because of the gap, air leaks into the nasal cavity resulting in a hypernasal voice resonance and nasal emissions while talking. Secondary effects of VPI include speech articulation errors (e.g., distortions, substitutions, and omissions) and compensatory misarticulations and mispronunciations (e.g., glottal stops and posterior nasal fricatives). Possible treatment options include speech therapy, prosthetics, augmentation of the posterior pharyngeal wall, lengthening of the palate, and surgical procedures.
Submucous cleft palate (SMCP) can also occur, which is a cleft of the soft palate with a split uvula, a furrow along the midline of the soft palate, and a notch in the back margin of the hard palate. The diagnosis of SMCP often occurs late in children as a result of the nature of the cleft. While the muscles of the soft palate are not joined, the mucosal membranes covering the roof of the mouth appear relatively normal and intact
Complications
A baby being fed using a customized bottle. The upright sitting position allows gravity to help the baby swallow the milk more easily.
Cleft may cause problems with feeding, ear disease, speech, socialization, and cognition.
Due to lack of suction, an infant with a cleft may have trouble feeding. An infant with a cleft palate will have greater success feeding in a more upright position. Gravity will help prevent milk from coming through the baby's nose if he/she has cleft palate. Gravity feeding can be accomplished by using specialized equipment, such as the Haberman Feeder. Another equipment commonly used for gravity feeding is a customized bottle with a combination of nipples and bottle inserts. A large hole, crosscut, or slit in the nipple, a protruding nipple and rhythmically squeezing the bottle insert can result in controllable flow to the infant without the stigma caused by specialized equipment.
Individuals with cleft also face many middle ear infections which may eventually lead to hearing loss. The Eustachian tubes and external ear canals may be angled or tortuous, leading to food or other contamination of a part of the body that is normally self-cleaning. Hearing is related to learning to speak. Babies with palatal clefts may have compromised hearing and therefore, if the baby cannot hear, it cannot try to mimic the sounds of speech. Thus, even before expressive language acquisition, the baby with the cleft palate is at risk for receptive language acquisition. Because the lips and palate are both used in pronunciation, individuals with cleft usually need the aid of a speech therapist.
Tentative evidence has found that those with clefts perform less well at language.
Causes
The development of the face is coordinated by complex morphogenetic events and rapid proliferative expansion, and is thus highly susceptible to environmental and genetic factors, rationalising the high incidence of facial malformations. During the first six to eight weeks of pregnancy, the shape of the embryo's head is formed. Five primitive tissue lobes grow
a) one from the top of the head down towards the future upper lip (frontonasal prominence);
b-c) two from the cheeks, which meet the first lobe to form the upper lip (maxillar prominence);
d-e) and just below, two additional lobes grow from each side, which form the chin and lower lip (mandibular prominence).
If these tissues fail to meet, a gap appears where the tissues should have joined (fused). This may happen in any single joining site, or simultaneously in several or all of them. The resulting birth defect reflects the locations and severity of individual fusion failures (e.g., from a small lip or palate fissure up to a completely malformed face).
The upper lip is formed earlier than the palate, from the first three lobes named a to c above. Formation of the palate is the last step in joining the five embryonic facial lobes, and involves the back portions of the lobes b and c. These back portions are called palatal shelves, which grow towards each other until they fuse in the middle. This process is very vulnerable to multiple toxic substances, environmental pollutants, and nutritional imbalance. The biologic mechanisms of mutual recognition of the two cabinets, and the way they are glued together, are quite complex and obscure despite intensive scientific research.
Orofacial clefts may be associated with a syndrome (syndromic) or may not be associated with a syndrome (nonsyndromic). Syndromic clefts are part of syndromes that are caused by a variety of factors such as environment and genetics or an unknown cause. Nonsyndromic clefts, which are not as common as syndromic clefts, also have a genetic cause
Genetics
Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present. A number of genes are involved including cleft lip and palate transmembrane protein 1 and GAD1, One study found an association between mutations in the HYAL2 gene and cleft lip and cleft palate formation.
Syndromes
The Van der Woude Syndrome is caused by a specific variation in the gene IRF6 that increases the occurrence of these deformities threefold.
Another syndrome, Siderius X-linked intellectual disability, is caused by mutations in the PHF8 gene (OMIM 300263); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild mental retardation.
In some cases, cleft palate is caused by syndromes that also cause other problems:
Stickler's Syndrome can cause cleft lip and palate, joint pain, and myopia.
Loeys-Dietz syndrome can cause cleft palate or bifid uvula, hypertelorism, and aortic aneurysm.
Hardikar syndrome can cause cleft lip and palate, Hydronephrosis, Intestinal obstruction and other symptoms.
Cleft lip/palate may be present in many different chromosome disorders including Patau Syndrome (trisomy 13).
• Malpuech facial clefting syndrome
• Hearing loss with craniofacial syndromes
• Popliteal pterygium syndrome
• Treacher Collins syndrome
• Pierre Robin syndrome
Diagnosis
Traditionally, the diagnosis is made at the time of birth by physical examination. Recent advances in prenatal diagnosis have allowed obstetricians to diagnose facial clefts in utero with ultrasonography.
Clefts can also affect other parts of the face, such as the eyes, ears, nose, cheeks, and forehead. In 1976, Paul Tessier described fifteen lines of cleft. Most of these craniofacial clefts are even rarer and are frequently described as Tessier clefts using the numerical locator devised by Tessier.
Allori, AC; Mulliken, JG; Meara, JG (2017). "Classification of Cleft Lip/Palate: Then and Now". Cleft Palate-Craniofacial Journal. 54 (2): 175–188. doi:10.1597/14-080. PMID 26339868.
Beaty TH, Ruczinski I, Murray JC, et al. (May 2011). "Evidence for gene-environment interaction in a genome wide study of isolated, non-syndromic cleft palate". Genet Epidemiol. 35 (6): 469–78. doi:10.1002/gepi.20595. PMC 3180858. PMID 21618603.
Boklage, Charles E. (2010). How new humans are made cells and embryos, twins and chimeras, left and right, mind/selfsoul, sex, and schizophrenia. Singapore: World Scientific. p. 283. ISBN 9789812835147. Archived from the original on 2017-09-10.
Boyles AL, Wilcox AJ, Taylor JA, et al. (2008). "Folate and One-Carbon Metabolism Gene Polymorphisms and Their Associations With Oral Facial Clefts". American Journal of Medical Genetics. 146A (4): 440–9. doi:10.1002/ajmg.a.32162. PMC 2366099. PMID 18203168.
Cox, T. C. (2004). "Taking it to the max: The genetic and developmental mechanisms coordinating midfacial morphogenesis and dysmorphology". Clin. Genet. 65 (3): 163–176. doi:10.1111/j.0009-9163.2004.00225.x. PMID 14756664.
Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: synthesizing genetic and environmental influences". Nature Reviews Genetics. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089.
Facts about Cleft Lip and Cleft Palate. October 20, 2014. Archived from the original on 8 May 2015. Retrieved 8 May 2015.
Hanny, KH (2015). "Late detection of cleft palate". European Journal of Pediatrics. 175 (1): 71–80. doi:10.1007/s00431-015-2590-9. PMC 4709386. PMID 26231683.
Hill JS (2001). "Velopharyngeal insufficiency: An update on diagnostic and surgical techniques". Current Opinion in Otolaryngology & Head and Neck Surgery. 9 (6): 365–8. doi:10.1097/00020840-200112000-00005. Archived from the original on 2012-07-10.
Kanno K, Suzuki Y, Yamada A, Aoki Y, Kure S, Matsubara Y (May 2004). "Association between nonsyndromic cleft lip with or without cleft palate and the glutamic acid decarboxylase 67 gene in the Japanese population". American Journal of Medical Genetics. 127A (1): 11–6. doi:10.1002/ajmg.a.20649. PMID 15103710.
Kim EK, Khang SK, Lee TJ, Kim TG (May 2010). "Clinical features of the microform cleft lip and the ultrastructural characteristics of the orbicularis oris muscle". Cleft Palate Craniofac. J. 47 (3): 297–302. doi:10.1597/08-270.1. PMID 19860522. permanent dead link
Kronwith SD, Quinn G, McDonald DM, et al. (1990). "Stickler's syndrome in the Cleft Palate Clinic". J Pediatr Ophthalmol Strabismus. 27 (5): 265–7. PMID 2246742.
M, Sriram Bhat; M, Sriram Bhat (2014). SRB's Surgical Operations: Text & Atlas. JP Medical Ltd. p. 414. ISBN 9789350251218.
Meeks, Naomi J.L.; Saenz, Margarita; Tsai, Anne Chun-Hui; Elias, Ellen R. (2018), Hay, Jr., William W.; Levin, Myron J.; Deterding, Robin R.; Abzug, Mark J. (eds.), "Genetics & Dysmorphology", Current Diagnosis & Treatment: Pediatrics (24 ed.), McGraw-Hill Education, retrieved 2019-08-06
Meeks, Naomi J.L.; Saenz, Margarita; Tsai, Anne Chun-Hui; Elias, Ellen R. (2018), Hay, Jr., William W.; Levin, Myron J.; Deterding, Robin R.; Abzug, Mark J. (eds.), "Genetics & Dysmorphology", Current Diagnosis & Treatment: Pediatrics (24 ed.), McGraw-Hill Education, retrieved 2019-08-06
Cleft lip and palate are the result of tissues of the face not joining properly during development. As such, they are a type of birth defect. The cause is unknown in most cases. Risk factors include smoking during pregnancy, diabetes, obesity, an older mother, and certain medications (such as some used to treat seizures). Cleft lip and cleft palate can often be diagnosed during pregnancy with an ultrasound exam.
A cleft lip or palate can be successfully treated with surgery. This is often done in the first few months of life for cleft lip and before eighteen months for cleft palate. Speech therapy and dental care may also be needed. With appropriate treatment, outcomes are good.
Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world. CL is about twice as common in males as females, while CP without CL is more common in females. In 2017, it resulted in about 3,800 deaths globally, down from 14,600 deaths in 1990. The condition was formerly known as a "hare-lip" because of its resemblance to a hare or rabbit, but that term is now generally considered to be offensive.
Signs and symptoms
Cleft lipIf the cleft does not affect the palate structure of the mouth, it is referred to as cleft lip. Cleft lip is formed in the top of the lip as either a small gap or an indentation in the lip (partial or incomplete cleft), or it continues into the nose (complete cleft). Lip cleft can occur as a one-sided (unilateral) or two-sided (bilateral) condition. It is due to the failure of fusion of the maxillary prominence and medial nasal processes (formation of the primary palate).
A mild form of a cleft lip is a microform cleft. A microform cleft can appear as small as a little dent in the red part of the lip or look like a scar from the lip up to the nostril. In some cases muscle tissue in the lip underneath the scar is affected and might require reconstructive surgery. It is advised to have newborn infants with a microform cleft checked with a craniofacial team as soon as possible to determine the severity of the cleft.
Cleft palate
Cleft palate is a condition in which the two plates of the skull that form the hard palate (roof of the mouth) are not completely joined. The soft palate is in these cases cleft as well. In most cases, cleft lip is also present.
Palate cleft can occur as complete (soft and hard palate, possibly including a gap in the jaw) or incomplete (a 'hole' in the roof of the mouth, usually as a cleft soft palate). When cleft palate occurs, the uvula is usually split. It occurs due to the failure of fusion of the lateral palatine processes, the nasal septum, or the median palatine processes (formation of the secondary palate).
The hole in the roof of the mouth caused by a cleft connects the mouth directly to the inside of the nose.
Note: the next images show the roof of the mouth. The top shows the nose, the lips are colored pink. For clarity the images depict a toothless infant.
A result of an open connection between the mouth and inside the nose is called velopharyngeal inadequacy (VPI). Because of the gap, air leaks into the nasal cavity resulting in a hypernasal voice resonance and nasal emissions while talking. Secondary effects of VPI include speech articulation errors (e.g., distortions, substitutions, and omissions) and compensatory misarticulations and mispronunciations (e.g., glottal stops and posterior nasal fricatives). Possible treatment options include speech therapy, prosthetics, augmentation of the posterior pharyngeal wall, lengthening of the palate, and surgical procedures.
Submucous cleft palate (SMCP) can also occur, which is a cleft of the soft palate with a split uvula, a furrow along the midline of the soft palate, and a notch in the back margin of the hard palate. The diagnosis of SMCP often occurs late in children as a result of the nature of the cleft. While the muscles of the soft palate are not joined, the mucosal membranes covering the roof of the mouth appear relatively normal and intact
Complications
A baby being fed using a customized bottle. The upright sitting position allows gravity to help the baby swallow the milk more easily.
Cleft may cause problems with feeding, ear disease, speech, socialization, and cognition.
Due to lack of suction, an infant with a cleft may have trouble feeding. An infant with a cleft palate will have greater success feeding in a more upright position. Gravity will help prevent milk from coming through the baby's nose if he/she has cleft palate. Gravity feeding can be accomplished by using specialized equipment, such as the Haberman Feeder. Another equipment commonly used for gravity feeding is a customized bottle with a combination of nipples and bottle inserts. A large hole, crosscut, or slit in the nipple, a protruding nipple and rhythmically squeezing the bottle insert can result in controllable flow to the infant without the stigma caused by specialized equipment.
Individuals with cleft also face many middle ear infections which may eventually lead to hearing loss. The Eustachian tubes and external ear canals may be angled or tortuous, leading to food or other contamination of a part of the body that is normally self-cleaning. Hearing is related to learning to speak. Babies with palatal clefts may have compromised hearing and therefore, if the baby cannot hear, it cannot try to mimic the sounds of speech. Thus, even before expressive language acquisition, the baby with the cleft palate is at risk for receptive language acquisition. Because the lips and palate are both used in pronunciation, individuals with cleft usually need the aid of a speech therapist.
Tentative evidence has found that those with clefts perform less well at language.
Causes
The development of the face is coordinated by complex morphogenetic events and rapid proliferative expansion, and is thus highly susceptible to environmental and genetic factors, rationalising the high incidence of facial malformations. During the first six to eight weeks of pregnancy, the shape of the embryo's head is formed. Five primitive tissue lobes grow
a) one from the top of the head down towards the future upper lip (frontonasal prominence);
b-c) two from the cheeks, which meet the first lobe to form the upper lip (maxillar prominence);
d-e) and just below, two additional lobes grow from each side, which form the chin and lower lip (mandibular prominence).
If these tissues fail to meet, a gap appears where the tissues should have joined (fused). This may happen in any single joining site, or simultaneously in several or all of them. The resulting birth defect reflects the locations and severity of individual fusion failures (e.g., from a small lip or palate fissure up to a completely malformed face).
The upper lip is formed earlier than the palate, from the first three lobes named a to c above. Formation of the palate is the last step in joining the five embryonic facial lobes, and involves the back portions of the lobes b and c. These back portions are called palatal shelves, which grow towards each other until they fuse in the middle. This process is very vulnerable to multiple toxic substances, environmental pollutants, and nutritional imbalance. The biologic mechanisms of mutual recognition of the two cabinets, and the way they are glued together, are quite complex and obscure despite intensive scientific research.
Orofacial clefts may be associated with a syndrome (syndromic) or may not be associated with a syndrome (nonsyndromic). Syndromic clefts are part of syndromes that are caused by a variety of factors such as environment and genetics or an unknown cause. Nonsyndromic clefts, which are not as common as syndromic clefts, also have a genetic cause
Genetics
Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present. A number of genes are involved including cleft lip and palate transmembrane protein 1 and GAD1, One study found an association between mutations in the HYAL2 gene and cleft lip and cleft palate formation.
Syndromes
The Van der Woude Syndrome is caused by a specific variation in the gene IRF6 that increases the occurrence of these deformities threefold.
Another syndrome, Siderius X-linked intellectual disability, is caused by mutations in the PHF8 gene (OMIM 300263); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild mental retardation.
In some cases, cleft palate is caused by syndromes that also cause other problems:
Stickler's Syndrome can cause cleft lip and palate, joint pain, and myopia.
Loeys-Dietz syndrome can cause cleft palate or bifid uvula, hypertelorism, and aortic aneurysm.
Hardikar syndrome can cause cleft lip and palate, Hydronephrosis, Intestinal obstruction and other symptoms.
Cleft lip/palate may be present in many different chromosome disorders including Patau Syndrome (trisomy 13).
• Malpuech facial clefting syndrome
• Hearing loss with craniofacial syndromes
• Popliteal pterygium syndrome
• Treacher Collins syndrome
• Pierre Robin syndrome
Diagnosis
Traditionally, the diagnosis is made at the time of birth by physical examination. Recent advances in prenatal diagnosis have allowed obstetricians to diagnose facial clefts in utero with ultrasonography.
Clefts can also affect other parts of the face, such as the eyes, ears, nose, cheeks, and forehead. In 1976, Paul Tessier described fifteen lines of cleft. Most of these craniofacial clefts are even rarer and are frequently described as Tessier clefts using the numerical locator devised by Tessier.
Allori, AC; Mulliken, JG; Meara, JG (2017). "Classification of Cleft Lip/Palate: Then and Now". Cleft Palate-Craniofacial Journal. 54 (2): 175–188. doi:10.1597/14-080. PMID 26339868.
Beaty TH, Ruczinski I, Murray JC, et al. (May 2011). "Evidence for gene-environment interaction in a genome wide study of isolated, non-syndromic cleft palate". Genet Epidemiol. 35 (6): 469–78. doi:10.1002/gepi.20595. PMC 3180858. PMID 21618603.
Boklage, Charles E. (2010). How new humans are made cells and embryos, twins and chimeras, left and right, mind/selfsoul, sex, and schizophrenia. Singapore: World Scientific. p. 283. ISBN 9789812835147. Archived from the original on 2017-09-10.
Boyles AL, Wilcox AJ, Taylor JA, et al. (2008). "Folate and One-Carbon Metabolism Gene Polymorphisms and Their Associations With Oral Facial Clefts". American Journal of Medical Genetics. 146A (4): 440–9. doi:10.1002/ajmg.a.32162. PMC 2366099. PMID 18203168.
Cox, T. C. (2004). "Taking it to the max: The genetic and developmental mechanisms coordinating midfacial morphogenesis and dysmorphology". Clin. Genet. 65 (3): 163–176. doi:10.1111/j.0009-9163.2004.00225.x. PMID 14756664.
Dixon MJ, Marazita ML, Beaty TH, Murray JC (March 2011). "Cleft lip and palate: synthesizing genetic and environmental influences". Nature Reviews Genetics. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089.
Facts about Cleft Lip and Cleft Palate. October 20, 2014. Archived from the original on 8 May 2015. Retrieved 8 May 2015.
Hanny, KH (2015). "Late detection of cleft palate". European Journal of Pediatrics. 175 (1): 71–80. doi:10.1007/s00431-015-2590-9. PMC 4709386. PMID 26231683.
Hill JS (2001). "Velopharyngeal insufficiency: An update on diagnostic and surgical techniques". Current Opinion in Otolaryngology & Head and Neck Surgery. 9 (6): 365–8. doi:10.1097/00020840-200112000-00005. Archived from the original on 2012-07-10.
Kanno K, Suzuki Y, Yamada A, Aoki Y, Kure S, Matsubara Y (May 2004). "Association between nonsyndromic cleft lip with or without cleft palate and the glutamic acid decarboxylase 67 gene in the Japanese population". American Journal of Medical Genetics. 127A (1): 11–6. doi:10.1002/ajmg.a.20649. PMID 15103710.
Kim EK, Khang SK, Lee TJ, Kim TG (May 2010). "Clinical features of the microform cleft lip and the ultrastructural characteristics of the orbicularis oris muscle". Cleft Palate Craniofac. J. 47 (3): 297–302. doi:10.1597/08-270.1. PMID 19860522. permanent dead link
Kronwith SD, Quinn G, McDonald DM, et al. (1990). "Stickler's syndrome in the Cleft Palate Clinic". J Pediatr Ophthalmol Strabismus. 27 (5): 265–7. PMID 2246742.
M, Sriram Bhat; M, Sriram Bhat (2014). SRB's Surgical Operations: Text & Atlas. JP Medical Ltd. p. 414. ISBN 9789350251218.
Meeks, Naomi J.L.; Saenz, Margarita; Tsai, Anne Chun-Hui; Elias, Ellen R. (2018), Hay, Jr., William W.; Levin, Myron J.; Deterding, Robin R.; Abzug, Mark J. (eds.), "Genetics & Dysmorphology", Current Diagnosis & Treatment: Pediatrics (24 ed.), McGraw-Hill Education, retrieved 2019-08-06
Meeks, Naomi J.L.; Saenz, Margarita; Tsai, Anne Chun-Hui; Elias, Ellen R. (2018), Hay, Jr., William W.; Levin, Myron J.; Deterding, Robin R.; Abzug, Mark J. (eds.), "Genetics & Dysmorphology", Current Diagnosis & Treatment: Pediatrics (24 ed.), McGraw-Hill Education, retrieved 2019-08-06
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