Hyperekplexia and the α1 Subunit Glycine Receptor Gene (GLRA1)

Hyperekplexia or startle disease (SD) is a rare neurological disorder characterized by an exaggerated and persistent startle response to unexpected visual, auditory, and proprioceptive stimuli. Hypertonia can also be present, particularly in the neonatal period.¹ Two different forms of SD have been recognized. The major form is characterized by excessive startle reactions followed by a short period of generalized hypertonia and the minor form, where hypertonia is not observed. Although in most of the families who have been described, SD shows autosomal dominant inheritance with almost complete penetrance,² evidence for recessive transmission has also been reported.³ Two different missense mutations (G1192A, G1192T) in the same base pair of exon 6 of GLRA1 have been found in 4 of 7 American families with SD.⁴ Independent investigators^3,5 have also found these mutations segregating in Swiss (G1192T) and British (G1192A) families with SD. In addition, Rees et al