ALAGILLE SYNDROME - FAMILY STUDIES

Alagille syndrome (AGS) is one of the major forms of chronic liver dis ease in childhood with severe morbidity and a mortality of 10 to 20%. It is characterised by cholestasis of variable severity with paucity o f interlobular bile ducts and anomalies of the cardiovascular system, skeleton, eyes, and face. Previous studies suggest a wide variation in the expression of the disease and a high incidence of new mutations. To determine more accurately the rate of new mutations and to develop criteria for detecting the disorder in parents we systematically inves tigated parents in 14 families with an affected child. Clinical examin ation was supplemented by liver function tests, echocardiography, radi ographic examination of the spine and forearm, ophthalmological assess ment, and chromosome analysis. Six parents had typical anomalies in tw o or more systems pointing to the presence of autosomal dominant inher itance. Systematic screening of parents for the features defined in th is study should improve the accuracy of genetic counselling.