From VACTERL-H to heterotaxy: variable expressivity of ZIC3-related disorders.

The ZIC3 gene encodes a zinc finger protein which functions as a transcription factor in early stages of left-right body axis formation. Mutations in this X-linked gene cause a variety of clinical manifestations including heterotaxy, complex or isolated heart defect as well as other midline urogenital and hindgut malformations. We report a four generation family with X-linked heterotaxy associated with a deletion of the ZIC3 gene at Xq26.3. The index fetus of our proband showed classical features of heterotaxy while her maternal uncle and one brother had imperforate anus and her other brother had features suggestive of VACTERL-H without heterotaxy. A 1.4 Mb deletion in Xq26.3 including the ZIC3 gene was found in the fetus. Six females in the family were found to be asymptomatic carriers. Our report indicates that some of the cases with VACTERL-H syndrome may be caused by a mutation or deletion of the ZIC3 gene.