Unique family with Townes-Brocks syndrome, SALL1 mutation, and cardiac defects

Townes-Brocks syndrome (TBS) is a condition with imperforate anus, hand ano malies, and ear malformations with sensorineural hearing loss. Many cases a re sporadic. Within and between families, the phenotype displays striking v ariability. Recently, the disease-causing gene for TBS was identified as SA LL1, a zinc finger transcription factor. Here, we report a three-generation family with seven affected individuals who have a novel SALL1 mutation. Un ique cardiac anomalies seen in this family include lethal truncus arteriosu s in one patient and a lethal complicated defect, including pulmonary valve atresia, in a second patient. These severe cardiac anomalies have not prev iously been reported in a familial case of TBS. This family and a review of the literature indicate that cardiac evaluation is warranted in all indivi duals with this disorder. In addition, hypoplastic thumbs were seen in two individuals in this family and should, therefore, be considered a true feat ure of TBS. (C) 2001 Wiley-Liss. Inc.