Multifactorial dependence of congenital malformations

Abstract

Birth prevalence of congenital malformations ranges between 2 and 6%, depending on the population. Congenital malformations significantly contribute to the causes of early and late infant mortality as well as to the development of severe handicaps. These facts make congenital malformations a serious medical and social problem. In many cases, the type and the severity of the defect together with anatomical location determine the fate of an infant in the very beginning of life. And this is the case independently of the quality and the method of treatment applied. These facts are the major motivation for the attempt to develop an effective method of primary prevention of congenital malformations. The effectiveness of this approach is strictly related to the amount of information on the etiology of congenital anomalies. The clinical and etiologic heterogeneity of congenital malformations is the major factor responsible for the inability to provide a clear and unequivocal definition of causes and to eliminate them from the environment. In addition, in a substantial number of malformations no etiologic factor could be identified. A special problem is created by malformations with a "threshold effect", where the disease liability results from genetic susceptibility and environmental triggering factors. If both components, genetic and environmental, exceed a certain threshold, the malformation appears. The paper discusses the major etiologic factors and inheritance patterns of congenital malformations and the practical implications for genetic counselling.