Abstract

We report on a 4-year-old girl who presented with microcephaly, multiple minor anomalies of face and limbs, congenital heart defect, hypotonia, neuropsychomotor delay, deafness and seizures. A GTG-banded karyotype identified an additional fragment of unknown origin on the terminal region of 4p. Parental karyotypes were normal. FISH analysis using a whole chromosome paint probe for chromosome 4 and subtelomere probes showed a signal on the entire add (4) chromosome and loss of the 4p subtelomere region, respectively. Additional analysis using microsatellite markers for chromosome 4 and whole-genome array comparative genomic hybridization (array-CGH) identified a duplication of the region 4p13 4p16.3. Her karyotype was thus interpreted as an inverted duplication with terminal deletion of 4p: 46,XX,der(4)(:p13 p16.3::p16.3 qter). The clinical features of our patient differed from those typically observed in Wolf-Hirschhorn syndrome and were more compatible with duplication 4(p14 p16.3), with preservation of the WHS critical region.