Hyperekplexia 3

A number sign (#) is used with this entry because hyperekplexia-3 (HKPX3) is caused by homozygous or compound heterozygous mutation in the GLYT2 gene (SLC6A5; 604159) on chromosome 11p15. There is also evidence that a heterozygous mutation in the SLC6A5 gene can result in HKPX3.

For a general description and a discussion of genetic heterogeneity of hyperekplexia, see HKPX1 (149400).

Clinical Features

Rees et al. (2006) reported 7 patients, including 2 sibs, with hyperekplexia. Affected individuals presented with neonatal hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. Notably, in some cases, symptoms resolved in the first year of life.

Inheritance

In 5 families with HKPX3 reported by Rees et al. (2006), the transmission pattern was consistent with autosomal recessive inheritance. The mother of 1 patient, who was heterozygous for a truncating SLC6A5 mutation (604159.0002) had nocturnal myoclonus and a nervous disposition, suggesting a partial phenotype. Another patient had a heterozygous mutation, consistent with autosomal dominant inheritance.

Molecular Genetics

In 6 patients, including 2 brothers, with hyperekplexia-3, Rees et al. (2006) identified homozygous or compound heterozygous mutations in the SLC6A5 gene (see, e.g., 604159.0001-604159.0007). An additional patient with the disorder was found to carry a heterozygous mutation (604159.0008), consistent with autosomal dominant inheritance.