Alagille syndrome in a family with duplication 20p11

Alagille syndrome (arteriohepatic dysplasia, AHD) is a well defined genetic disorder with five major features: distinctive facies, cardiovascular anomalies, paucity of interlobular bile ducts (PILBD), ocular anomalies and minor skeletal malformations. Repeatedly, structural anomalies of 20p, in most cases a deletion, have been described in patients with Alagille syndrome. We report a three generation family with AHD presenting with typical facial dysmorphology, cardiac and ocular lesions but without clinical signs of liver manifestation. Two infants died from a complex cardiovascular malformation consisting of pulmonary valve atresia, hypoplasia of the pulmonary arteries and VSD. The diagnosis was not appreciated until ocular anomalies were found in the father and the distinctive facies became apparent in the daughter. Chromosome region 20p could not be interpreted precisely by high resolution banding. Using in situ hybridization a duplication 20p11.21-p11.23 was found segregating with the disorder in the family.