How to cite this article: South ST, Bleyl SB, Carey JC. 2007. Two unique patients with novel microdeletions in 4p16.3 that exclude the WHS critical regions: Implications for critical region designation. Am J Med Genet Part A 143A:2137–2142.
Two unique patients with novel microdeletions in 4p16.3 that exclude the WHS critical regions: Implications for critical region designation†
Article first published online: 14 AUG 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 143A, Issue 18, pages 2137–2142, 15 September 2007
How to Cite
South, S. T., Bleyl, S. B. and Carey, J. C. (2007), Two unique patients with novel microdeletions in 4p16.3 that exclude the WHS critical regions: Implications for critical region designation. Am. J. Med. Genet., 143A: 2137–2142. doi: 10.1002/ajmg.a.31900
- Issue published online: 17 AUG 2007
- Article first published online: 14 AUG 2007
- Manuscript Accepted: 17 MAY 2007
- Manuscript Received: 29 DEC 2006
- Wolf-Hirschhorn syndrome critical region;
- 4p deletion;
- ring chromosome;
Wolf-Hirschhorn syndrome (WHS) is characterized by growth delay, developmental delay, hypotonia, seizures, feeding difficulties, and characteristic facial features. Deletion of either of two critical regions (WHSCR and WHSCR-2) within chromosome band 4p16.3 has been proposed as necessary for the minimal clinical manifestations of WHS and controversy remains regarding their designation. We describe two patients with novel terminal microdeletions in 4p16.3 who lack the characteristic facial features but do show some of the more nonspecific manifestations of WHS. The first patient had a ring chromosome 4 with an intact 4q subtelomere and a terminal 4p microdeletion of approximately 1.27–1.46 Mb. This deletion was distal to both proposed critical regions. The second patient had a normal karyotype with a terminal 4p microdeletion of approximately 1.78 Mb. This deletion was distal to WHSCR and the breakpoint was near or within the known distal boundary for WHSCR-2. Both patients showed significant postnatal growth delay, mild developmental delays and feeding difficulties. Their facial features were not typical for WHS. The phenotype of the first patient may have been influenced by the presence of a ring chromosome. Seizures were absent in the first patient whereas the second patient had a complex seizure disorder. Characterization of these patients supports the hypothesis that a gene in WHSCR-2, LETM1, plays a direct role in seizure development, and demonstrates that components of the WHS phenotype can be seen with deletions distal to the known boundaries of the two proposed critical regions. These patients also emphasize the difficulty of mapping clinical manifestations common to many aneusomy syndromes. © 2007 Wiley-Liss, Inc.