Inv dup del(4)(:p13 → p16.3::p16.3 → qter) in a girl without typical manifestations of Wolf–Hirschhorn syndrome

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. © 2009 Wiley‐Liss, Inc.