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BMC Neurology
Published in: BMC Neurology 1/2012

Open Access 01-12-2012 | Research article

A novel syndrome of lethal familial hyperekplexia associated with brain malformation

Authors: Mohammed Zein Seidahmed, Mustafa A Salih, Omer B Abdulbasit, Meeralebbae Shaheed, Khalid Al Hussein, Abeer M Miqdad, Abdullah K Al Rasheed, Anas M Alazami, Ibrahim A Alorainy, Fowzan S Alkuraya

Published in: BMC Neurology | Issue 1/2012

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Abstract

Background

Hyperekplexia (HPX) is a rare non-epileptic disorder manifesting immediately after birth with exaggerated persistent startle reaction to unexpected auditory, somatosensory and visual stimuli, and non-habituating generalized flexor spasm in response to tapping of the nasal bridge (glabellar tap) which forms its clinical hallmark. The course of the disease is usually benign with spontaneous amelioration with age. The disorder results from aberrant glycinergic neurotransmission, and several mutations were reported in the genes encoding glycine receptor (GlyR) α1 and β subunits, glycine transporter GlyT2 as well as two other proteins involved in glycinergic neurotransmission gephyrin and collybistin.

Methods

The phenotype of six newborns, belonging to Saudi Arabian kindred with close consanguineous marriages, who presented with hyperekplexia associated with severe brain malformation, is described. DNA samples were available from two patients, and homozygosity scan to determine overlap with known hyperkplexia genes was performed.

Results

The kindred consisted of two brothers married to their cousin sisters, each with three affected children who presented antenatally with excessive fetal movements. Postnatally, they were found to have microcephaly, severe hyperekplexia and gross brain malformation characterized by severe simplified gyral pattern and cerebellar underdevelopment. The EEG was normal and they responded to clonazepam. All of the six patients died within six weeks. Laboratory investigations, including metabolic screen, were unremarkable. None of the known hyperkplexia genes were present within the overlapping regions of homozygosity between the two patients for whom DNA samples were available.

Conclusions

We present these cases as a novel syndrome of lethal familial autosomal recessive hyperekplexia associated with microcephaly and severe brain malformation.
Appendix
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Metadata
Title
A novel syndrome of lethal familial hyperekplexia associated with brain malformation
Authors
Mohammed Zein Seidahmed
Mustafa A Salih
Omer B Abdulbasit
Meeralebbae Shaheed
Khalid Al Hussein
Abeer M Miqdad
Abdullah K Al Rasheed
Anas M Alazami
Ibrahim A Alorainy
Fowzan S Alkuraya
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2012
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-12-125

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