Hyperekplexia is a rare, potentially treatable neurogenetic condition: two major genes of effect are described—one postsynaptic (GLRA1) the other presynaptic (SLC6A5). It is currently not known whether a genetic diagnosis can predict clinical presentation. Sixty individuals were identified from a genetic database and the referring clinicians were contacted using a standard questionnaire; replies for 48 (80%) were received. 37 people (from 29 families) had mutations in GLRA1 and 11 (10 families) in SLC6A5. They all exhibited classical symptoms of hyperekplexia and clonazepam is the treatment of choice (92% had a sustained benefit). We found no genetic evidence for “major” or “minor” forms of hyperekplexia. Apnoea attacks are common (40%) and delayed milestones, learning difficulties or speech and language impairment was seen in 44%. Patients with SLC6A5 mutations were significantly more likely than those with GLRA1 mutations: to have had serious infantile apnoeas (p<0.005); and to have both apnoeas and developmental difficulties (p<0.01). The developmental delay demonstrated in some patients may represent failure of neurogenesis in a glycine-poor environment. There is a compelling argument for early genetic testing for symptomatic neonates and preconception counselling for parents who carry SLC6A5 mutations. Ninety per cent of neonates with hyperekplexia due to SLC6A5 mutations have multiple serious apnoeas and cognitive development is impaired in two thirds.
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