Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: a contiguous gene syndrome
- PDF / 252,742 Bytes
- 4 Pages / 595.276 x 790.866 pts Page_size
- 122 Downloads / 195 Views
BRIEF REPORT
Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: a contiguous gene syndrome Joanna Kenny & Melissa M. Lees & Susan Drury & Angela Barnicoat & William van’t Hoff & Rodger Palmer & Deborah Morrogh & Jonathan J. Waters & Nicholas J. Lench & Detlef Bockenhauer
Received: 6 January 2011 / Revised: 14 March 2011 / Accepted: 16 March 2011 / Published online: 20 May 2011 # IPNA 2011
Abstract Sotos syndrome is characterized by overgrowth, a typical facial appearance, and learning difficulties. It is caused by heterozygous mutations, including deletions, of NSD1 located at chromosome 5q35. Here we report two unrelated cases of Sotos syndrome associated with nephrocalcinosis. One patient also had idiopathic infantile hypercalcemia. Genetic investigations revealed heterozygous deletions at 5q35 in both patients, encompassing NSD1 and SLC34A1 (NaPi2a). Mutations in SLC34A1 have previously been associated with hypercalciuria/nephrolithiasis. Our cases suggest a contiguous gene deletion syndrome including NSD1 and SLC34A1 and provide a potential genetic basis for idiopathic infantile hypercalcemia. Keywords Idiopathic infantile hypercalcemia . Nephrocalcinosis . SLC34A1 . Sotos syndrome
greater than two standard deviations from the mean at birth and characteristic facial features [1]. The majority of patients also exhibit some form of developmental delay, which can range from mild to severe. Additional features may include advanced bone age, seizures, cardiac and renal anomalies, and scoliosis. The majority of cases are caused by mutations in NSD1 (nuclear receptor SET domaincontaining protein), which occur mostly de novo and up to 10% of cases are caused by micro-deletions of 5q35 [2]. Genitourinary abnormalities are reported in approximately 15% of patients, most commonly vesico-ureteric reflux [1]. Here, we report on two cases of Sotos syndrome complicated by nephrocalcinosis plus infantile hypercalcemia in one patient. The identification of a chromosome 5q35 microdeletion in both cases encompassing SLC34A1 and NSD1, provides a potential explanation for this extended phenotypic spectrum of Sotos syndrome.
Introduction Methods Sotos syndrome is an autosomal dominant overgrowth syndrome with length or head circumference typically
J. Kenny : M. M. Lees : S. Drury : A. Barnicoat : R. Palmer : D. Morrogh : J. J. Waters : N. J. Lench North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK W. van’t Hoff : D. Bockenhauer (*) Department of Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK e-mail: [email protected]
We performed a retrospective note review of two patients with Sotos syndrome and concomitant nephrocalcinosis. Genetic investigations were performed as part of their clinical care [3]. Array comparative genomic hybridization was performed using the Nimblegen 135 K Whole Genome Tiling array (Roche NimbleGen, Inc, Madison, USA) according to the manufacturer"s instructions.
Data Loading...
