Conflict of interest: none.
Co-occurrence of 22q11 deletion syndrome and hdr syndrome
Version of Record online: 5 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 10, pages 2576–2581, October 2013
How to Cite
2013. Co-occurrence of 22q11 deletion syndrome and HDR syndrome. Am J Med Genet Part A 161A:2576–2581., , , , , , , .
- Issue online: 17 SEP 2013
- Version of Record online: 5 AUG 2013
- Manuscript Accepted: 16 MAY 2013
- Manuscript Received: 23 NOV 2012
- Ministry of Health, Labour and Welfare
- Japan Science and Technology Agency
- Japan Society for the Promotion of Science
- Strategic Research Promotion of Yokohama City University
- Japan Epilepsy Research Foundation
- Naito Foundation
- Takeda Science Foundation
- Yokohama Foundation for Advancement of Medical Science
- Hayashi Memorial Foundation for Female Natural Scientists
- whole genome SNP assay;
- 22q11 deletion syndrome;
- HDR syndrome;
- double mutations;
22q11 deletion syndrome is one of the most common chromosomal deletion syndromes and is usually caused by a 1.5–3.0 Mb deletion at chromosome 22q11.2. It is characterized by hypocalcemia resulting from hypoplasia of the parathyroid glands, hypoplasia of the thymus, and defects of the cardiac outflow tract. We encountered a Japanese boy presenting with an unusually severe phenotype of 22q11 deletion syndrome, including progressive renal failure and severe intellectual disabilities. Diagnostic testing using fluorescent in situ hybridization revealed deletion of the 22q11 region, but this did not explain the additional complications. Copy number analysis was therefore performed using whole genome single nucleotide polymorphism (SNP) assay, which identified an additional de novo deletion at 10p14. This region is the locus for hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome caused by haploinsufficiency of GATA3. Together, these two syndromes sufficiently explain the patient's phenotype. This is the first known case report of the co-occurrence of 22q11 deletion syndrome and HDR syndrome. As the two syndromes overlap clinically, this study indicates the importance of carrying out careful clinical and genetic assessment of patients with atypical clinical phenotypes or unique complications. Unbiased genetic analysis using whole genome copy number SNP arrays is especially useful for detecting such rare double mutations. © 2013 Wiley Periodicals, Inc.