Mutations in the glycine receptor α1 subunit (GLRA1) gene in hereditary hyperekplexia pedigrees: evidence for non-penetrance of mutation Y279C

Abstract
The first pedigree (Fam-1) contains 20 members over three generations with 10 affected subjects (fig 1A). The female proband (III.13) from family 1 was prone to fall in response to any unexpected stimulus, such as a touch or a sharp sound, from the time she started walking. Falling was the result of momentary generalised stiffness of her trunk and limbs with loss of postural control. This symptom was present in a large number of male and female relatives, as shown in fig1A, consistent with autosomal dominant inheritance of the disorder. Falling in affected members of the family was sudden, unpredictable, and uncontrollable. Falling was not accompanied by loss of consciousness and affected members were able to rise from the ground immediately after falling. The diagnosis of hyperekplexia was made after publication of the paper by Morley et al.10 The proband was treated with clonazepam and remained symptomless for over 13 years.