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1、Cleft Lip & Palate,Eduardo D. Rosas Blum, MD August 7, 2007,25yo G1 P1 delivers a full-term infant after 12hrs of uneventful labor. The infant was found to have a cleft lip and palate. How should the care for this infant, and his mother, be?,While on call,Birth defects,Malformations alterations in n
2、ormal development Deformations abnormal mechanical force on an otherwise normal fetus Disruptions disruption of an otherwise normal developmental process,Introduction,Most common craniofacial malformation Cleft lip with or without cleft palate (CL/P) or isolated cleft palate (CP). CL/P and CP differ
3、 with respect to Embryology, etiology, candidate genes, associated abnormalities, and recurrence risk.,Prevalence,CL/P is more common than CP and varies by ethnicity. CL/P High in American Indians and Asians (1/500 newborns) Low in American blacks (1/2000 newborns) Intermediate level in Caucasians (
4、1/1000 newborns) Isolated CP occurs in only 1/2500 newborns and does not display variation by ethnicity.,Cleft Lip,Complete closure at 35 days postconception: 7 weeks from the LMP. Lateral nasal, median nasal, and maxillary mesodermal processes merge. Failure of closure can produce unilateral, bilat
5、eral, or median lip clefting. Left side unilateral cleft is the most common.,Cleft lip Severity,Mild, involving only the lip Extend into the palate and midface thereby affecting the nose, forehead, eyes, and brain.,Cleft Palate,Lack of fusion of the palatal shelves. Abnormalities in programmed cell
6、death may contribute to lack of palatal fusion(?). Isolated disruption of palate shelves can occur after closure of the lip Palatal closure is not completed until 9 weeks post-conception.,Etiology,Genes Control cell patterning, cell proliferation, extracellular communication, and differentiation Cle
7、fting usually represents a genetically complex event Single Mendelian disorders associated with clefting are rare 2 to 20 genes are thought to interact to result in facial clefting,Etiology,Dlx gene Direct the destination of the distal skeletogenic mesenchyme elements to the palate. Mutations of the
8、se genes result in isolated palatal defects. Sonic hedgehog gene Protein that mediates ectodermal functions, might regulate the outgrowth and fusion of the facial domains. TGF-alpha variant Receptor ligand, usually a rare variant of TGF-alpha Family histories of cleft defects Additive teratogenic ef
9、fect with agents such as cigarette smoking and alcohol,Etiology,TGF-beta-3 gene Expressed just prior to palatal fusion. Results in isolated cleft palate. IRF 6 Identified in autosomal dominant van der Woude syndrome.,Environmental agents,Several agents that are associated with an increased frequency
10、 of midfacial malformation. Medications phenytoin, sodium valproate, methotrexate. With corticosteroids there is no evidence of an increase in malformations. Possible association could not be excluded,Etiology,Cigarette smoking Noted with mothers of children with facial clefting, both CL/P and CP. T
11、eratogenesis has been attributed to hypoxia as well as a component of tobacco (cadmium). Alcohol Associated with an increased risk of fetal facial clefting. Alterations in cell membrane fluidity or reduced activity of specific enzymes such as superoxide dismutase. Folate deficiency Contributes to a
12、range of birth defects. Evidence is emerging for a similar association with the development of CL/P.,Prenatal Diagnosis,Diagnosed until the soft tissues of the fetal face can be clearly visualized sonographically (13 to 14 weeks). The majority of infants with cleft lip also have palatal involvement:
13、 85% of bilateral cleft lips 70% associated with cleft palate. Cleft palate with an intact lip comprises 27% of isolated CL/P,Prenatal Diagnosis,The sensitivity is highest when is associated with other structural anomalies. Isolated CL/P in a low risk population, the sensitivity may only reach 50 pe
14、rcent. Cleft palate with an intact lip is the most difficult orofacial malformation to diagnose prenatally. Detected in only 13 of 198 cases in one large series. Three-dimensional ultrasound, can provide a clear image of the malformation,Prenatal Diagnosis,Syndrome ?,A thorough examination of the ne
15、wborn or stillbirth is always warranted. Orofacial clefting is noted in over 300 syndromes. 3 deserve additional comment. frequency, variable presentations, and modes of inheritance,Deletion of chromosome 22q11,DeGeorge syndrome. Spectrum in addition to cleft palate: Conotruncal cardiac defects, thy
16、mic hypoplasia, and velopharyngeal webs. Majority of cases represent a new microdeletion In families with conotruncal malformations and/or CP, further evaluation is appropriate.,Oral-facial-digital syndrome, type I,X-linked dominant syndromes. Manifestations in affected females are variable and subt
17、le: hyperplastic frenula cleft tongue cleft lip/palate digital anomalies,Treacher-Collins syndrome,Autosomal dominant disorder Downward slanting palpebral fissures, micrognathia, dysplastic ears, and deafness. Mental development is normal. The mutations appear to increase cell death in the prefusion neural folds. A family history with deafness, ear abnormalities, or CP.,
