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Unexpected high frequency of de novo unbalanced translocations in patients with Wolf-Hirschhorn syndrome (WHS)
  1. *Institut für Humangenetik, Universitätsklinikum Essen, Germany
  2. †Molekulare Humangenetik, Ruhr-Universität Bochum, Germany
  3. ‡Institut für Humangenetik und Anthropologie, Heinrich-Heine-Universität Düsseldorf, Germany
  4. §Abteilung Medizinische Genetik, Altonaer Kinderkrankenhaus, Hamburg, Germany
  5. ¶Abteilung für Medizinische Genetik, Universität Rostock, Germany
  1. Dr Wieczorek, Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany, dagmar.wieczorek{at}

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Editor—Wolf-Hirschhorn syndrome (WHS), first described independently in 1965 by Wolf et al 1 and Hirschhorn et al,2 is a well defined multiple congenital anomalies/mental retardation syndrome resulting from deletion involving chromosomal band 4p16.3 with a minimal critical region of 165 kb.3

Different mechanisms are responsible for WHS, including terminal 4p deletions, familial translocations, and de novo complex chromosomal rearrangements such as unbalanced translocations. The frequency of translocations in WHS as a result of parental chromosomal translocations is estimated to be 5 to 13%,4 5 whereas the rate of sporadic translocations in WHS was suggested to be 1.6% (2/120).5 A few isolated cases with de novo translocations5-12 resulting in WHS have been described recently. The trisomic segment, however, often could not be defined owing to the lack of specific cytogenetic techniques.5 6 8 13-15

Here we report six patients with unbalanced translocations, t(4p;8p) and t(4p;7p), respectively, and discuss their phenotypic abnormalities.

Since 1996 we have performed clinical, molecular, cytogenetic, and molecular-cytogenetic investigations in a total of 22 patients with clinical signs of Wolf-Hirschhorn syndrome. These patients were all seen by one of the authors. In five of them (22%), the combination of cytogenetic and molecular investigations showed a de novo unbalanced translocation; in a sixth patient the de novo occurrence of the translocation could not be confirmed because no blood sample from the father was available.

The clinical findings of patients 1-5, who all presented with characteristic features of WHS, are summarised in table 1. Patient 6 (CL220585/87E1624) had some additional findings listed in table1.

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Table 1

Clinical findings in patients 1-5 with t(4;8) and patient 6 with t(4;7)

The combination of Hirschsprung disease and hydrocephalus was suggestive of CRASH syndrome in patient 6, but SSCP analysis of theL1CAM gene …

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