Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients

• Published in: Brain & development (Tokyo. 1979) Vol. 39; no. 4; pp. 306 - 311
• Main Authors: Masri, Amira, Chung, Seo-Kyung, Rees, Mark I
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2017
• Subjects: Adolescent; Apnea; Child; Child, Preschool; Consanguinity; Diagnostic Errors; Epilepsy - diagnosis; Female; Follow-Up Studies; Genotype; Glycine Plasma Membrane Transport Proteins - genetics; Humans; Hyperekplexia; Hyperekplexia - diagnosis; Hyperekplexia - genetics; Hyperekplexia - physiopathology; Hyperekplexia - therapy; Infant; Infant, Newborn; Jordan; Male; Misdiagnosis; Neurology; Nose tap; Phenotype; Receptors, Glycine - genetics; Retrospective Studies; Young Adult; Misdiagnosis; Nose tap; Consanguinity; Apnea; Jordan; Hyperekplexia
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2016.10.010

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.