Conflicts of interest: nothing to declare.
Bilateral Pheochromocytomas, Hemihyperplasia, and Subtle Somatic Mosaicism: The Importance of Detecting Low-Level Uniparental Disomy
Article first published online: 26 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 5, pages 993–1001, May 2013
How to Cite
2013. Bilateral pheochromocytomas, hemihyperplasia, and subtle somatic mosaicism: The importance of detecting low-level uniparental disomy. Am J Med Genet Part A 161A:993–1001., , , , , , , , , , , , , , , .
- Issue published online: 22 APR 2013
- Article first published online: 26 MAR 2013
- Manuscript Accepted: 1 DEC 2012
- Manuscript Received: 13 MAR 2012
- NIH. Grant Numbers: T32GM008638, NIH/NICHD K08HD055488
- uniparental disomy;
We report on a patient with early onset pediatric bilateral pheochromocytomas caused by mosaic chromosome 11p15 paternal uniparental isodisomy (UPD). Hemihyperplasia of the arm was diagnosed in a 4-month-old female and clinical methylation testing for 11p15 in the blood was normal, with a reported detection threshold for mosaicism of 20%. She was subsequently diagnosed at 18 months with bilateral pheochromocytomas. Single-nucleotide polymorphism (SNP) array analysis of pheochromocytoma tissue demonstrated mosaic deletions of 8p12pter, 21q21.1qter, 22q11.23qter; commonly seen in pheochromocytomas. In addition, mosaic 11p15.3pter homozygosity was noted. Molecular testing for other causes of pheochromocytomas was normal, suggesting that 11p15 homozygosity was the primary event. Subsequent SNP array analysis of skin fibroblasts from the hyperplastic side demonstrated 5% mosaic paternal UPD for 11p15. We have subsequently used SNP array analysis to identify four patients with subtle hemihyperplasia with low-level mosaic UPD that was not detected by methylation analysis. Given the increased sensitivity of SNP array analysis to detect UPD along with the increased incidence of tumorigenesis in these UPD patients, we suggest that it has high utility in the clinical work-up of hemihyperplasia. The present case also suggests that 11p15 paternal UPD may be an under-detected mechanism of sporadic pheochromocytoma in the pediatric population. Furthermore, a review of the literature suggests that patients with 11p15 paternal UPD may present after 8 years of age with pheochromocytoma and raises the possibility that ultrasound screening could be considered beyond 8 years of age in this subset of hemihyperplasia and Beckwith–Wiedemann syndrome patients. © 2013 Wiley Periodicals, Inc.