O SlideShare utiliza cookies para otimizar a funcionalidade e o desempenho do site, assim como para apresentar publicidade mais relevante aos nossos usuários. Se você continuar a navegar o site, você aceita o uso de cookies. Leia nosso Contrato do Usuário e nossa Política de Privacidade.
O SlideShare utiliza cookies para otimizar a funcionalidade e o desempenho do site, assim como para apresentar publicidade mais relevante aos nossos usuários. Se você continuar a utilizar o site, você aceita o uso de cookies. Leia nossa Política de Privacidade e nosso Contrato do Usuário para obter mais detalhes.
Variations clefting congenital deformityduring gestation. Common birth defects---complex etiology Immediately recognizable disruptions Cleft is a fissure or opening—a gap Previously known as harelip
Also affect other parts of the face, suchas the eyes, ears, nose, cheeks, andforehead. In 1976, Paul Tessier described fifteenlines of cleft. Facial clefting is the second mostcommon congenital deformity (afterclubfoot).
Approximately 1 in 700 live birthsThe frequency of CLP differs by sex2:1 male to female ratio for cleft lipalone1:2 male to female ratio for cleftpalate alone2:1 ratio of left to right sided cleftsamong unilateral cleft lip cases
Prevalence rates varies within differentethnic groups. Highest prevalence rates - Native Americansand Asians Lowest prevalance rates- Africans Native Americans: 3.74/1000 Japanese: 0.82/1000 to 3.36/1000 Chinese: 1.45/1000 to 4.04/1000 Caucasians: 1.43/1000 to 1.86/1000 Latin Americans: 1.04/1000 Africans: 0.18/1000 to 1.67/1000
Rate of occurrence of CPO is similarfor Caucasians, Africans, NorthAmerican natives, Japanese andChinese.The trait is dominant.
Involves the vermilion border of the upperlip and may extend through the lip towardthe nostril Affects the shape of the nose Can be either unilateral or bilateral Unilateral clefts usually occur on the left side Bilateral clefts usually involve the palate Cleft lip by itself is rare
OrbicularisorisThe orbicularis oris musclesrun parallel to the edge ofthe cleft and inserts intothe alar margin. . There isno muscle in the prolabiumin bilateral cleft
A condition in which the two plates of theskull that form the hard palate (roof of themouth) are not completely joined. Soft palate also involved Presence of cleft lip Connection of the mouth directly to thenasal cavity.
Development of the faceFormed between the 5th and 8th weeks ofgestationCoordinated by complex morphogenetic events rapid proliferative expansionhighly susceptible to environmental and geneticfactors
Results from the fusion of Two mandibular processes One frontonasal process Two maxillary processes Cleft lip occurs when the fusionprocess between the frontnasalmasses and the maxillaryprocesses is interrupted
Not a major cause of mortality in developedcountries, CLP does cause considerablemorbidity to affected children and imposes asubstantial financial risk for families with aconcomitant societal burden problems with feeding speaking social integration middle ear infections which may eventuallylead to hearing loss Velopharyngeal Incompetence (VPI)
Components1. Velum2. Muscles in theback of the throat
The velum needs tobe closed and theoral and nasalcavities separatedwhen we swallowand during theproduction of mostEnglish speechsounds
At the time of birth by physical examination Recent advances --- diagnose facial clefts inutero
CLP can occur:Syndromic CLPNon-syndromic CLP
Cleft lip with or without cleft palate --- morethan 200 specific genetic syndromes Isolated cleft palate --- more than 400syndromes Proportion of orofacial clefts associatedwith specific syndromes --- 5% and 7%.
Hydrolethalus Van der Woude/poplitealpterygium X-linked mental retardationand CL/P Gorlin CLP – ectodermal dysplasia HYLS1 IRF6 PHF8 PTCH1 PVRL1
Oculofaciocardiodental CHARGE Lethal and Escobar multiplepterygium Stickler type 1 Stickler type 2 Stickler type 3 Desmosterolosis Smith-Lemli-Opitz Miller Craniofrontonasal BCOR CHD7 CHRNG COL2A1 COL11A1 COL11A2 DHCR24 DHCR7 DHODH EFNB1
Approximately 70% of cases of CLP occur asisolated entities Defects arise early in embryologicaldevelopment, have a complex etiology withboth genetic and environmentalcontributions and modest recurrence rates Specific etiologic factors----difficult
A combination of: epidemiologic candidate gene genome-wide studies analysis of animal modelsprovided deeper insights into the causes of non-syndromic CLP.
Advent of the genomics era-- major advancesin identifying the causative genetic mutationsunderlying syndromic forms of CLP(http://www.ncbi.nlm.nih.gov/omim) In contrast: genetic heterogeneity departure from Mendelian inheritance patterns lack of (and expense of) genomic tools necessity for very large datasetsless progress in advancing of the genetic etiologyof non-syndromic CLP
Recent development of innovativeapproaches to phenotyping powerful genomic toolshas increased our understanding of non-syndromic CLP.
Much of the genetic variation for non-syndromic CLP -- regulatory elements Challenging to identify -- regulate genesacross substantial genomic distances Chromatin immunoprecipitation followed byNext Generation Sequence analysis -- highlysensitive method to accurately identifyenhancer elements
Estimates of the main effects of genes orenvironment could be biased if interactionis not taken into account Understanding of cause and pathogenesis isenhanced by such studies Findings of interaction work can informdecisions about public health strategies
Markers in the GSTT1 (glutathione S-transferase theta) or NOS3 (nitric oxidesynthase 3) --- influence risk of CL/P in thepresence of maternal smoking Smoking ----IRF6 gene Multivitamins and IRF6 Alcohol consumption--- ADH1C
These are common congenital deformitiesthat often affect speech, hearing, andfeeding; and may at times lead to airwaycompromise. The otolaryngologist is a key member of thecleft palate team, and is in a unique positionto identify and manage many of theseproblems .
Global approaches for the identification andranking of candidate genes Improved methods for analyzing functionalelements controlling gene expression Integration of genetic and environmental riskusing epigenetics, systems biology, geneexpression and epidemiology will both bettercharacterize etiologies, as well as provideaccess to better clinical care and prevention