Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients

Brain Dev. 2017 Apr;39(4):306-311. doi: 10.1016/j.braindev.2016.10.010. Epub 2016 Nov 11.

Abstract

Background: Hyperekplexia, is a rare disorder characterized by excessive startle response to acoustic, visual, or other stimuli. It is inherited in autosomal recessive and dominant pattern.

Objective: To describe the clinical and genetic features of hyperekplexia in Jordanian patients.

Methods: This retrospective study includes all patients with proved genetic diagnosis of hyperekplexia who presented to our clinic at the Jordan University Hospital from January 2001 through July 2015.

Results: A total of 16 children from 12 families were included. The total follow up period ranged from one to eleven years. The majority of the patients (13/16=81.3%) were initially misdiagnosed as epilepsy. All patients had excessive startle response since birth. Tonic-apneic spells occurred in 15/16=93.8% patients. Fourteen patients (45/16=87.5%) received clonazepam. Stopping clonazepam by three years of age failed in 11/14 (78.6%) due to reappearance of tonic-apneic spells (8/14=57.1%), recurrent falling (10/14=71.4%) or due to both reasons (5/14=35.7%). Delayed motor development occurred in 7/16 (43.8%), speech delay in 4/16 (25.0%), global developmental delay in 1/16 (6.3%), and autism spectrum disorder in 1/16 (6.3%) patient. The mode of inheritance is autosomal recessive in all 12/12 (100%) families. Mutations in GLRA1 gene was present in 9/16 (56.3%); the most common mutation was in p.G254D (4/9; 44.5%). Mutations in the GLRB gene was present in 4/16 (25.0%) patients and the SLC6A5 gene in 3/16 (18.8%) patients.

Conclusion: The clinical presentation of hyperekplexia in Jordanian patients is manifested by tonic-apneic spells in all homozygous patients. The persistence of apneic spells and recurrent falls throughout childhood necessitate continuous treatment and surveillance.

Keywords: Apnea; Consanguinity; Hyperekplexia; Jordan; Misdiagnosis; Nose tap.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Consanguinity
  • Diagnostic Errors
  • Epilepsy / diagnosis
  • Female
  • Follow-Up Studies
  • Genotype
  • Glycine Plasma Membrane Transport Proteins / genetics
  • Humans
  • Hyperekplexia / diagnosis
  • Hyperekplexia / genetics*
  • Hyperekplexia / physiopathology*
  • Hyperekplexia / therapy
  • Infant
  • Infant, Newborn
  • Jordan
  • Male
  • Phenotype
  • Receptors, Glycine / genetics
  • Retrospective Studies
  • Young Adult

Substances

  • GLRA1 protein, human
  • GLRB protein, human
  • Glycine Plasma Membrane Transport Proteins
  • Receptors, Glycine
  • SLC6A5 protein, human