Other entities represented in this entry:
Cytogenetic location: 20q12-q13.12 Genomic coordinates (GRCh38): 20:39,000,001-47,800,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 20q12-q13.12 | Parasomnia, sleepwalking type | 613938 | Autosomal dominant; Multifactorial | 2 |
Sleepwalking (SW) is a disorder in which a series of complex behaviors are initiated during slow-wave (non-REM) sleep and result in walking during sleep (American Academy of Sleep Medicine, 2005). It is a parasomnia, defined as a clinical disorder resulting in undesirable physical phenomena that occur predominantly during sleep. Parasomnias are not abnormalities of the processes responsible for sleep and wake states (summary by Hublin and Kaprio, 2003). Sleepwalking is more common in childhood (up to 26%), and usually resolves in adolescence; however, it can persist into adulthood (3%) (Hublin et al., 1997).
Licis et al. (2011) reported a large 4-generation Caucasian family in which 9 individuals were affected with sleepwalking. All had onset of sleepwalking between age 4 and 10 years, and adults continued to have episodes into their thirties, although the frequency was decreased from childhood. Three individuals recalled episodes of sleep paralysis, and none had a history of seizures.
Sleepwalking episodes can be triggered by stressful factors, including family conflicts, job stress, sleep deprivation, and alcohol. Anxiety is a common personality trait associated with sleepwalking (Lecendreux et al., 2003).
Abe and Shimakawa (1966) observed an association between sleepwalking and sleeptalking (see 606840) in a study of 611 3-year-old Japanese children. The findings suggested that sleepwalking and sleeptalking may be different manifestations of a similar neurophysiologic deviation. Of 342 children for whom information on both parents was available, the authors found that the offspring of sleepwalkers were more likely to sleepwalk. In addition, the incidence of sleepwalking was higher in children with a history of seizures. An autosomal recessive pattern of inheritance with incomplete penetrance was postulated.
Sleep terrors, or night terrors, are episodic events of extreme vocalization, motility, and autonomic discharge associated with intense fear that occur suddenly out of slow-wave sleep. Like sleepwalking, sleep terrors are classified as an arousal type of parasomnia. By studying the families of 25 probands with sleepwalking and 27 with night terrors, Kales et al. (1980) found that 80% of the sleepwalking pedigrees and 96% of the night terror pedigrees had 1 or more affected individuals other than the proband. Moreover, these affected family members had sleepwalking, night terrors, or both, suggesting a common genetic predisposition. First-degree relatives of sleepwalkers had at least a 10-fold increased risk of being affected than the general population. Kales et al. (1980) suggested that sleepwalking may be a more prevalent and less severe manifestation of the same substrate that underlies night terrors. Phenotypic expression may be influenced by environmental factors.
Dogu and Pressman (2011) noted that hereditary factors are believed to play an important role in sleepwalking with both recessive (Abe and Shimakawa, 1966) and multifactorial (Kales et al., 1980) inheritance patterns having been reported. It is likely that there is a genetic predisposition or susceptibility to developing the disorder.
Among 646 twin pairs, including 398 monozygotic (MZ) twin pairs, Bakwin (1970) found that sleepwalking was more common in MZ (7.1%) than in dizygotic (DZ) twins (6.0%). Sleepwalking was twice as frequent in MZ boys as in MZ girls and DZ boys. Nine of 19 MZ twin pairs were concordant, whereas only 1 of 14 DZ pairs was concordant. In addition, when a parent had a history of sleepwalking, the chances of a child also being a sleepwalker were 6 times as great as when neither parent had sleepwalked. The findings suggested a genetic basis for sleepwalking.
By studying the families of 25 probands with sleepwalking and 27 with night terrors, Kales et al. (1980) concluded that transmission pattern was not consistent with X-linked, autosomal dominant, or autosomal recessive inheritance; the authors postulated a multifactorial mode of inheritance.
In a Finnish twin pair study of 1,045 MZ and 1,899 DZ adult twin pairs, Hublin et al. (1997) found that sleepwalking in adulthood had occurred in 3.9% of men and in 3.1% of women. There was no significant difference in sleepwalking between MZ and DZ twins in either childhood or adulthood. However, the concordance rate for sleepwalking was 0.55 for MZ and 0.35 for DZ pairs. For adults with sleepwalking, the concordance rate was 0.32 for MZ and 0.06 for DZ pairs. The proportion of total phenotypic variance attributed to genetic influences was estimated to be 66% in men and 57% in women in childhood sleepwalking, and 80% in men and 36% in women in adult sleepwalking. Hublin et al. (1997) suggested that there are substantial genetic effects in sleepwalking in both childhood and adulthood.
The transmission pattern of sleepwalking in the large Caucasian family reported by Licis et al. (2011) was consistent with autosomal dominant inheritance with reduced penetrance.
By genomewide linkage analysis of a large Caucasian family with autosomal dominant inheritance of sleepwalking, Licis et al. (2011) found linkage to a locus on chromosome 20q12-q13.12 (maximum multipoint lod score of 3.44; maximum 2-point lod score of 3.56). Recombination analysis delineated a 5.8-cM (4.4-Mb) region. Sequencing of 10 genes in the candidate region, including the ADA gene (608958), did not reveal any mutations.
Genetic Heterogeneity
Lecendreux et al. (2003) found an association between HLA-DQB1*0501 (604305) and sleepwalking in a study of 60 affected Caucasian patients and 60 Caucasian controls: 21 (35.0%) sleepwalkers were DQB1*0501 positive compared to 8 (13.3%) controls (odds ratio of 3.5; corrected p less than 0.07). The transmission-disequilibrium test showed excess transmission was for DQB1*05 and *04 alleles in familial cases. Sequence analysis indicated that the ser74 residue in the second exon shared by all DQB1*05 and *04 alleles was 20 times transmitted compared to 4 times nontransmitted (p = 0.001) in familial cases. These findings suggested that specific HLA-DQB1 alleles may be implicated in disorders of motor control during sleep. Dogu and Pressman (2011) noted that the association with HLA-DQB1*05 ser74 variant has not been replicated.
Abe, K., Shimakawa, M. Predisposition to sleep-walking. Psychiat. Neurol. 152: 306-312, 1966.
American Academy of Sleep Medicine. International Classification of Sleep Disorders, Revised: Diagnostic and Coding Manual. Chicago: American Academy of Sleep Medicine (pub.) 2005.
Bakwin, H. Sleep-walking in twins. Lancet 2: 446-447, 1970. [PubMed: 4195120] [Full Text: https://doi.org/10.1016/s0140-6736(70)90058-9]
Dogu, O., Pressman, M. R. Identification of sleepwalking gene(s): not yet, but soon? Neurology 76: 12-13, 2011. [PubMed: 21205687] [Full Text: https://doi.org/10.1212/WNL.0b013e318203e9c0]
Hublin, C., Kaprio, J., Partinen, M., Heikkila, K., Koskenvuo, M. Prevalence and genetics of sleepwalking: a population-based twin study. Neurology 48: 177-181, 1997. [PubMed: 9008515] [Full Text: https://doi.org/10.1212/wnl.48.1.177]
Hublin, C., Kaprio, J. Genetic aspects and genetic epidemiology of parasomnias. Sleep Med. Rev. 7: 413-421, 2003. [PubMed: 14573377] [Full Text: https://doi.org/10.1053/smrv.2001.0247]
Kales, A., Soldatos, C. R., Bixler, E. O., Ladda, R. L., Charney, D. S., Weber, G., Schweitzer, P. K. Hereditary factors in sleepwalking and night terrors. Brit. J. Psychiat. 137: 111-118, 1980. [PubMed: 7426840] [Full Text: https://doi.org/10.1192/bjp.137.2.111]
Lecendreux, M., Bassetti, C., Dauvilliers, Y., Mayer, G., Neidhart, E., Tafti, M. HLA and genetic susceptibility to sleepwalking. Molec. Psychiat. 8: 114-117, 2003. [PubMed: 12556916] [Full Text: https://doi.org/10.1038/sj.mp.4001203]
Licis, A. K., Desruisseau, D. M., Yamada, K. A., Duntley, S. P., Gurnett, C. A. Novel genetic findings in an extended family pedigree with sleepwalking. Neurology 76: 49-52, 2011. [PubMed: 21205695] [Full Text: https://doi.org/10.1212/WNL.0b013e318203e964]