Manjunath Nimmakayalu and Nathan Noble equally contributed to this work.
Article first published online: 28 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Special Issue: SPECIAL ISSUE: GROWTH CHARTS IN GENETIC SYNDROMES
Volume 158A, Issue 11, pages 2767–2774, November 2012
How to Cite
Nimmakayalu, M., Noble, N., Horton, V. K., Willing, M., Copeland, S., Sheffield, V., Nagy, P. L., Wassink, T., Patil, S. and Shchelochkov, O. A. (2012), 2q24 deletions: Further characterization of clinical findings and their relation to the SCN cluster. Am. J. Med. Genet., 158A: 2767–2774. doi: 10.1002/ajmg.a.35362
How to Cite this Article: Nimmakayalu M, Noble N, Horton V, Willing M, Copeland S, Sheffield V, Nagy P, Wassink T, Patil S, Shchelochkov O. 2012. 2q24 Deletions: Further characterization of clinical findings and their relation to the SCN cluster. Am J Med Genet Part A 158A: 2767–2774.
- Issue published online: 17 OCT 2012
- Article first published online: 28 SEP 2012
- Manuscript Accepted: 6 FEB 2012
- Manuscript Received: 29 AUG 2011
- growth retardation;
- Dravet syndrome;
- SCN cluster;
- array comparative genomic hybridization (aCGH)
As the resolution of molecular cytogenetic methods continues to improve, it has become increasingly possible to refine genotype–phenotype correlations based upon gene involvement. We report three new patients with nonrecurrent deletions involving subbands of 2q24. These patients were referred for evaluation of developmental delay, but were found to have unique, nonoverlapping clinical features. Patient 1 presented with infantile seizures, microcephaly, and brain anomalies, along with facial dysmorphism, growth retardation, neuromuscular scoliosis, and later with developmental regression. Array comparative genomic hybridization (aCGH) detected an 8 Mb interstitial deletion encompassing the neuronal sodium channel (SCN) gene cluster. Patient 2 presented with growth retardation, congenital heart defect, and hypotonia. Patient 3 presented with developmental delay and behavioral problems. Patients 2 and 3 had no history of seizures, microcephaly, or brain anomalies and were found to have deletions of 2q24, ∼8 Mb and <500 kb respectively, centromeric to and outside the SCN cluster. It has been demonstrated that mutations and copy number variants (CNVs) affecting the SCN gene cluster result in severe, early-onset seizures. It is however, less clear whether haploinsufficiency of regions outside the SCN cluster may result in phenotypically recognizable and clinically significant features. We discuss additional dosage sensitive genes that may exist outside the SCN cluster. Our and published data indicate that 2q24 deletions not involving the SCN cluster are associated with fewer neurobehavioral problems, but may predispose to congenital malformations. © 2012 Wiley Periodicals, Inc.