Cleft Lip and Palate
- Cleft lip
- Deformity of the upper lip that may include a discontinuity of vermilion, skin, muscle, and mucosa as well as the underlying gingiva and bone
- May be unilateral or bilateral
- A complete cleft extends into the nose. An incomplete cleft has a bridge of intact tissue between the oral and nasal cavities.
- Cleft palate
- May involve the gingiva, hard palate, and/or soft palate
- Represents a visible separation between the two halves of the roof of the mouth, involving mucosa, muscle, and often the bones of the hard palate
- A submucous cleft palate has intact mucosa, but the underlying muscle and bone are at least partially divided.
- Incidence of cleft lip with or without cleft palate is approximately 1 in 700 births.
- Isolated cleft palate is present in 1 in 2,000 births across races.
- Racial heterogeneity noted in cleft lip and palate (Asians, 2.1 in 1,000 births; Caucasians, 1 in 1,000; African-Americans, 0.41 in 1,000)
- Gender heterogeneity noted in Caucasians (male-to-female ratio: cleft lip with or without cleft palate, 1.5 to 2:1; cleft palate only, 0.7:1)
- Incidence of cleft lip with or without cleft palate increases with parental (especially paternal) age >30 years. Some association with low socioeconomic class may be nutrition-related.
- Some recognized patterns of malformation that include cleft lip and/or cleft palate may be caused by exposure to teratogens, but there is little evidence linking isolated clefts to exposure to any single teratogenic agent.
- Exceptions include phenytoin (use during pregnancy has been associated with a 10-fold increase in the incidence of cleft lip) and isotretinoin (~26 relative risk of congenital malformations including cleft palate).
- Incidence of cleft lip in infants born to mothers who smoke during pregnancy is twice that in those born to nonsmoking mothers.
- 1/3 of patients with cleft lip and/or cleft palate have a positive family history; positive family history is noted twice as often in cleft lip with or without cleft palate compared to cleft palate alone.
- The recurrence risk for cleft lip with or without cleft palate is 4% if one 1st-degree relative is affected and 9% if two are affected.
- Muscle fibers are atrophic and disorganized in the region of the cleft.
- Mitochondrial abnormalities are noted at the cleft margins by histochemical and electromyographic studies.
- Cleft lip may result from failure of the medial nasal and maxillary processes to join in utero or possibly from lack of adequate mesenchymal reinforcement, leading to subsequent breakdown and separation.
- Cleft palate results from failure of the palatal shelves to fuse.
- Prenatal dietary supplementation with folic acid and vitamin B6 has led to lower-than-expected incidence of cleft lip and cleft palate and to a decreased incidence of neural tube defects.
- Bilateral cleft lip is associated with cleft palate in 86% of cases. Unilateral cleft lip is associated with cleft palate in 68% of cases.
- Cleft lip/cleft palate is more common on the left, particularly in boys.
- Most clefts are nonsyndromic and may be either multifactorial in origin or the result of changes at a major single-gene locus.
- >400 genetic syndromes are associated with facial clefts.
- Among patients with clefts of the secondary palate alone, syndromes associated with microdeletions of chromosome 22q11.2 are currently the most common syndromic diagnoses.
- Collectively known as 22q11.2 deletion syndrome, includes velocardiofacial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome
- Inheritance is autosomal dominant with considerable variability in phenotypic expression, which may include facial dysmorphism, developmental delay, cardiovascular anomalies, immunologic abnormalities, cleft palate, and velopharyngeal dysfunction.
- Next most common syndrome associated with palatal clefts is Stickler syndrome:
- Characterized by autosomal dominance, cleft palate, epicanthal folds, flat facies, joint hyperflexibility, severe myopia, retinal detachment, and glaucoma
- Caused by a mutation of the gene for type 2 collagen (chromosome 12q)
- Most common syndrome associated with clefts of the lip and/or palate is van der Woude syndrome (autosomal dominant, lower lip pits, IRF6 mutations, 1q32).
- Other genetic syndromes associated with cleft lip and/or palate:
- CHARGE (coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness) syndrome has an autosomal dominant pattern of malformation with majority of patients having CHD7 microdeletion or mutation.
- Ectrodactyly–ectodermal dysplasia–cleft (EEC) syndrome is associated with p63 gene mutations.
- Smith-Lemli-Opitz (defect in cholesterol synthesis, DHCR7 gene mutation, 7q34)
- Pierre Robin sequence is a condition usually associated with a wide U-shaped cleft palate.
- Characterized by a small mandible, retropositioned tongue, and subsequent upper airway obstruction
- May occur in infants with or without genetic syndromes (Stickler most common)
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