A 2.8-Mb 4p16.3 terminal deletion, with proximal breakpoint at locus D4S182, was diagnosed by FISH in a 16-year-old boy who presented with a typical Wolf-Hirschhorn syndrome (WHS) phenotype. The deletion, which was maternally derived, was isolated, and a balanced translocation was ruled out in both parents by FISH with probe 33c6 (locus D4S43) falling within the patient's deletion interval, at a distance of about 2.3 Mb from the telomere. His older brother, who died from pneumonia at the age of 18 years, also presented with clinical signs consistent with WHS, including typical facial appearance and major malformations, but the genetic test was not performed. A smaller 4p deletion, spanning the 1.5 Mb region from locus D4S96 to the telomere was detected in the healthy mother. When critically analyzed, after the FISH results, she was noted to present with partial WHS facial "gestalt," borderline mental delay, a few episodes of seizures as a child, normal weight and head circumference, and height at the lower limit of normal range. This report highlights a previously undescribed mechanism of familial recurrence of a microdeletion syndrome. Potential meiotic amplification is to be considered for different subtelomeric deletions that are currently interpreted as population polymorphisms. At the same time, the present report adds new insights to mapping some peculiar WHS clinical signs, such as seizures and severe growth delay.
Copyright (c) 2007 Wiley-Liss, Inc.