title: Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Medicine, The University of Jordan, P.O. Box 1612 Code, 11941 Amman, Jordan. Electronic address: masriamira69@hotmail.com.
authors.forename: Amira
authors.initials: A
authors.lastname: Masri
authors.affiliation: Institute of Life Sciences, Swansea University Medical School, Swansea University, UK. Electronic address: s.chung@swansea.ac.uk.
authors.forename: Seo-Kyung
authors.initials: SK
authors.lastname: Chung
authors.affiliation: Institute of Life Sciences, Swansea University Medical School, Swansea University, UK. Electronic address: m.i.rees@swansea.ac.uk.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Rees
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003951:Diagnostic Errors; D004827:Epilepsy / Q000175:diagnosis; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D000071017:Hyperekplexia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D007597:Jordan; D008297:Male; D010641:Phenotype; D018009:Receptors, Glycine / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C000657604:GLRA1 protein, human; C114561:GLRB protein, human; D050487:Glycine Plasma Membrane Transport Proteins; D018009:Receptors, Glycine; C493271:SLC6A5 protein, human
keywords: Apnea; Consanguinity; Hyperekplexia; Jordan; Misdiagnosis; Nose tap