Our identification of a family with a high prevalence of sleepwalking confirms previous reports that support a strong genetic basis for this condition.2,–4
Various inheritance models have been proposed for sleepwalking, including multifactorial,3
and now autosomal dominant with reduced penetrance; it is possible that sleepwalking is genetically heterogeneous. Identification of the genes responsible for sleepwalking will be critical to improving our understanding the etiology, diagnosis, and treatment of this disorder. Optimizing treatment for sleepwalking is an important clinical objective due to its potential to cause injury. Our report of chromosome 20q12-q13.12 localization for a gene responsible for sleepwalking is a first step in the process of gene discovery.
The genetic bases of other sleep disorders have recently been described, including narcolepsy, restless legs syndrome, sleep apnea, and chronic primary insomnia.8
Symptoms of these sleep disorders were not endorsed by affected members of this family, and none of the genes identified for these disorders are located within our candidate region for sleepwalking on chromosome 20q12-q13.12.
The adenosine deaminase gene (ADA
) is the most likely candidate gene in the chromosome 20q12-q13.12 linkage interval due to its association with slow-wave sleep during which sleepwalking occurs. Inhibition of adenosine metabolism has been shown to increase EEG slow wave activity, and caffeine, an A1
adenosine receptor antagonist, reduces slow-wave sleep when administered prior to sleep onset.9
Individuals with the G/A genotype at nucleotide 22 in the coding region of ADA
demonstrated approximately 30 minutes more slow wave sleep on polysomnogram during an 8-hour sleep period than individuals with the G/G genotype.10
Slow-wave sleep duration may be a critical determinant of sleepwalking frequency, since it was found that longer duration of slow-wave sleep during recovery from sleep deprivation significantly increased the frequency of sleepwalking events.11
However, the less frequent and potentially at risk G/A ADA
genotype was present only once in this pedigree in an unaffected individual. Although we detected no coding mutations in sequencing the ADA
gene, it is possible that insertions or deletions or mutations in noncoding regulatory regions that alter ADA
expression are responsible for a sleepwalking phenotype. The remaining 27 candidate genes in the linkage region at chromosome 20q12-q13.12 may also have a role in causing sleepwalking.
An increased prevalence of sleepwalking was noted in males in this family, with several nonmanifesting carrier females. Other studies have described sex-related variation in sleepwalking. In the Finnish Twin Cohort study of 11,220 participants, there was a greater rate of childhood sleepwalking in girls but the opposite was true in adulthood.2
Also, an increased male-to-female ratio, in which 70% of the 60-patient cohort presenting with sleepwalking were male, was described in another study.4
The sleepwalking severity in members of the family described in the current study was atypical in that it continued with regularity into adulthood.2
Additional studies are needed to determine whether sleepwalking that persists into adulthood has different epidemiologic or genetic features than the more typical childhood-limited disorder.