SLEEP-RELATED HYPERMOTOR (HYPERKINETIC) EPILEPSY (SHE)

GENETICS

PATTERN OF INHERITANCE

The etiology of SHE may be genetic, genetic–structural, or acquired. Family history should be carefully sought, but is not expected in sporadic or acquired SHE. Familial SHE is usually inherited in an autosomal dominant fashion, with a penetrance of approximately 70%.

KNOWN GENES

Genetic causes include pathogenic variants in the GATOR1 complex genes (DEPDC5, NPRL2 or NPRL3), the acetylcholine receptor subunit genes (CHRNA4, less frequently CHRNB2 or CHRNA2) or in the sodium-activated potassium channel gene, KCNT1. Individuals with KCNT1 pathogenic variants have a more severe form of SHE, with intellectual impairment, psychosis, and sometimes regression. Rare families with autosomal recessive SHE are described, and pathogenic variants in PRIMA1 have been identified in one family.

FAMILY HISTORY OF SEIZURES/EPILEPSY

A family history of focal epilepsy may be present.