A unique phenotype of 2q24.3-2q32.1 duplication: early infantile epileptic encephalopathy without mesomelic dysplasia

J Child Neurol. 2014 Feb;29(2):260-4. doi: 10.1177/0883073813478659. Epub 2013 Mar 1.

Abstract

The voltage-gated sodium channel genes and HOXD genes are clustered on chromosome 2q, and duplication of this region is associated with 2 clinical phenotypes: early-onset epilepsy and mesomelic dysplasia Kantaputra type, respectively. We report a case involving 2q24.3-2q32.1 duplication encompassing both the voltage-gated sodium channel and HOXD gene clusters, which were detected by a comparative genomic hybridization array. The associated clinical features were early-infantile-onset epilepsy, hypoplastic left heart syndrome, and global developmental delay. However, no features of mesomelic dysplasia were found. A fluorescent in situ hybridization study showed that the noncontiguous insertion of the duplicated chromosome 2q segment into chromosome 6q was inherited from the father, who has a balanced insertional translocation. The unique genotype-phenotype correlation in the present case suggests that dosage-sensitive effects might apply only to the voltage-gated sodium channel genes.

Keywords: 2q duplication; HOXD; comparative genomic hybridization array; epilepsy; hypoplastic left heart syndrome; mesomelic dysplasia; sodium channel.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aicardi Syndrome / genetics*
  • Aicardi Syndrome / physiopathology
  • Brain / physiopathology
  • Chromosomes, Human, Pair 2 / genetics
  • Comparative Genomic Hybridization
  • Developmental Disabilities / genetics
  • Developmental Disabilities / physiopathology
  • Electroencephalography
  • Fathers
  • Humans
  • Hypoplastic Left Heart Syndrome / genetics
  • Hypoplastic Left Heart Syndrome / physiopathology
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Phenotype
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology
  • Translocation, Genetic
  • Trisomy / genetics*
  • Trisomy / physiopathology

Supplementary concepts

  • Chromosome 2, trisomy 2q
  • Infantile Epileptic-Dyskinetic Encephalopathy