CongenitalMalformation-ScopeoftheProblem.pptVIP

Congenital Malformation - Scope of the Problem Charles J. Macri MD Head, Division of Reproductive and Medical Genetics National Naval Medical Center Congenital Malformation - Scope of the Problem About 20-25% of perinatal deaths are due to lethal malformations birthweight 500-1500 grams - 10% birthweight 1500g - 50% Causes of Malformations Multifactorial - 20% Single-gene - 7.5% Chromosomal - 6% Infection - 2-3% Maternal diabetes - 1.5% Maternal medication - 1-2% Unknown - 50% Incidence of Malformation according to birth outcome Livebirths - 2.5% (74% of total) Stillbirths - 7% (2.5% of total) TABs - 9% (16.5% of total) SABs -12% (7.4% of total) Overall -3% N=8040 Brigham and Womens Hosp, 12 months Definitions Malformation Malformation sequence Deformation Disruption Deformation sequence Definitions Major malformation Minor malformation Syndrome Association Non-specificity of malformations Definitions: Malformation Morphologic defect of an organ or region due to an intrinsically abnormal developmental process (e.g. hypoplasia, incomplete closure, incomplete separation) Malformation Sequence Multiple defects derived from a single known or presumed structural defect Examples: meningomyeocele club foot, hip dislocation, hydrocephalus mandibular hypoplasia cleft palate (Robin sequence) Deformation Abnormal form or position of a body region caused by non-disruptive mechanical forces Examples: clubfoot, congenital hip dislocation Deformation Sequence Examples: Intrauterine constraint Robin sequence secondary to mandibular constraint Disruption Morphologic defect of an organ or region resulting from a breakdown of, or interference with an originally normal developmental process example: Amniotic Band Disruption Major Malformation Malformation of medical, surgical or cosmetic significance Minor Malformation Minor morphologic features of little or no known medical significance found in less than 4% of population Minor Variation “Norm