Download PDF
Neuropediatrics 2022; 53(02): 109-114
DOI: 10.1055/s-0041-1740551
Original Article

Epilepsy and Sleep in the ATR-X Syndrome

Petra van Mierlo
1   Department of Neurology, Academic Center for Epileptology Kempenhaeghe and Maastricht UMC + , Heeze, The Netherlands
2   Sleep Medicine Center; Kempenhaeghe, Heeze, The Netherlands
,
Hilde Braakman
1   Department of Neurology, Academic Center for Epileptology Kempenhaeghe and Maastricht UMC + , Heeze, The Netherlands
3   Department of Pediatric Neurology, Radboud University Medical Center and Donders Institute for Brain, Amalia Childreńs Hospital, Cognition and Behavior Nijmegen, Nijmegen, The Netherlands
,
Nele Vandenbussche
2   Sleep Medicine Center; Kempenhaeghe, Heeze, The Netherlands
4   Department of Pediatrics, Noorderhart Mariaziekenhuis, Pelt, Belgium
,
Helenius Jurgen Schelhaas
1   Department of Neurology, Academic Center for Epileptology Kempenhaeghe and Maastricht UMC + , Heeze, The Netherlands
5   Department of Neurology, Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands
,
Sigrid Pillen
6   Pediatric Sleep Expert Ltd, Mook, The Netherlands
7   Department of Electrical Engineering, Technical University Eindhoven, Eindhoven, The Netherlands
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Background This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome.

Design In this cross-sectional study, 37 participants with ATR-X syndrome aged 1.8 to 44 years were studied using a customized epilepsy questionnaire, review of electroencephalography (EEG) findings, the modified Sleep Questionnaire of Simonds and Parraga and 2-week sleep diary.

Results Eleven participants had a clinical diagnosis of generalized epilepsy (29.7%). Seizure types were generalized tonic-clonic seizures, absences, and myoclonia. Interictal EEG recordings in participants with GTCS showed no epileptic discharges in 78%. Similarly, EEG recordings during myoclonia and absences often demonstrated no epileptic discharges. Sleep problems (difficulty falling or maintaining sleep, and early awakening) were reported in 70%. Participants with reported sleep problems went to bed earlier (p = 0.027) and had a lower sleep efficiency (p < 0.01) than participants without sleep problems, but as a group they both had a sufficient total sleep time (9 hours and 52 minutes vs. 10 hours and 55 minutes). Sixteen participants (43.2) used medication to improve sleep (predominantly melatonin n = 10), being effective in only two.

Conclusion One-third of participants with ATR-X syndrome had a clinical diagnosis of epilepsy, but the absence of EEG abnormalities in suspected epileptic seizures questions this diagnosis in these patients. EEG recording during seizure like symptoms is warranted before making an epilepsy diagnosis. Seventy percent experienced sleep problems, although total sleep time was normal in most participants. Long bedtimes might have a negative influence on sleep efficiency.

Keywords

ATR-X syndrome - sleep - epilepsy - intellectual disability

Note

The work is performed at Kempenhaeghe, Heeze, the Netherlands.


Supplementary Material



Publication History

Received: 02 April 2021

Accepted: 12 November 2021

Article published online:
21 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Gibbons R. Alpha thalassaemia-mental retardation, X linked. Orphanet J Rare Dis 2006; 1: 15
    CrossrefPubMedGoogle Scholar
  • 2 Wada T, Gibbons RJ. ATR-X Syndrome. Genetics and Genomics of Neurobehavioral Disorders. Totowa, NJ: Humana Press; 2003: 309-334
    CrossrefGoogle Scholar
  • 3 Wilkie AO, Gibbons RJ, Higgs DR, Pembrey ME. X linked alpha thalassaemia/mental retardation: spectrum of clinical features in three related males. J Med Genet 1991; 28 (11) 738-741
    CrossrefPubMedGoogle Scholar
  • 4 Ogle R, DeSouza M, Cunningham C, Kerr B, Sillence D. X linked mental retardation with non-deletional alpha thalassaemia (ATR-X): further delineation of the phenotype. J Med Genet 1994; 31 (03) 245-247
    CrossrefPubMedGoogle Scholar
  • 5 Yun KW, Chae SA, Lee JJ. et al. The first case of X-linked Alpha-thalassemia/mental retardation (ATR-X) syndrome in Korea. J Korean Med Sci 2011; 26 (01) 146-149
    CrossrefPubMedGoogle Scholar
  • 6 Moncini S, Bedeschi MF, Castronovo P. et al. ATRX mutation in two adult brothers with non-specific moderate intellectual disability identified by exome sequencing. Meta Gene 2013; 1: 102-108
    CrossrefPubMedGoogle Scholar
  • 7 Donnai D, Clayton-Smith J, Gibbons RJ, Higgs DR. The non-deletion alpha thalassaemia/mental retardation syndrome: further support for X linkage. J Med Genet 1991; 28 (11) 742-745
    CrossrefPubMedGoogle Scholar
  • 8 Giacomini T, Vari MS, Janis S. et al. Epileptic encephalopathy, myoclonus-dystonia, and premature pubarche in siblings with a novel C-terminal truncating mutation in ATRX gene. Neuropediatrics 2019; 50 (05) 327-331
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Guerrini R, Shanahan JL, Carrozzo R, Bonanni P, Higgs DR, Gibbons RJ. A nonsense mutation of the ATRX gene causing mild mental retardation and epilepsy. Ann Neurol 2000; 47 (01) 117-121
    CrossrefPubMedGoogle Scholar
  • 10 Gibbons RJ, Brueton L, Buckle VJ. et al. Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X). Am J Med Genet 1995; 55 (03) 288-299
    CrossrefPubMedGoogle Scholar
  • 11 Ebishima Y, Misaki T, Owa K, Okuno T, Wada T, Suehiro Y. A case of X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome with repeated apnea attacks due to laryngomalacia. No To Hattatsu 2013; 45 (01) 44-48
    PubMedGoogle Scholar
  • 12 Carney CE, Buysse DJ, Ancoli-Israel S. et al. The consensus sleep diary: standardizing prospective sleep self-monitoring. Sleep (Basel) 2012; 35 (02) 287-302
    CrossrefPubMedGoogle Scholar
  • 13 Simonds JF, Parraga H. Prevalence of sleep disorders and sleep behaviors in children and adolescents. J Am Acad Child Psychiatry 1982; 21 (04) 383-388
    CrossrefPubMedGoogle Scholar
  • 14 Wiggs L, Stores G. Severe sleep disturbance and daytime challenging behaviour in children with severe learning disabilities. J Intellect Disabil Res 1996; 40 (Pt 6): 518-528
    CrossrefPubMedGoogle Scholar
  • 15 Wiggs L, Stores G. Sleep patterns and sleep disorders in children with autistic spectrum disorders: insights using parent report and actigraphy. Dev Med Child Neurol 2004; 46 (06) 372-380
    CrossrefPubMedGoogle Scholar
  • 16 Maas AP, Didden R, Korzilius H. et al. Psychometric properties of a sleep questionnaire for use in individuals with intellectual disabilities. Res Dev Disabil 2011; 32 (06) 2467-2479
    CrossrefPubMedGoogle Scholar
  • 17 Paruthi S, Brooks LJ, D'Ambrosio C. et al. Recommended amount of sleep for pediatric populations: a consensus statement of the American Academy of Sleep Medicine. J Clin Sleep Med 2016; 12 (06) 785-786
    CrossrefPubMedGoogle Scholar
  • 18 Morin CM, Espie CA. A Clinical Guide to Assessment and Treatment. New York: Kluwer Academic/Plenum Publishers; 2003
    Google Scholar
  • 19 Alexandru G, Michikazu S, Shimako H. et al. Epidemiological aspects of self-reported sleep onset latency in Japanese junior high school children. J Sleep Res 2006; 15 (03) 266-275
    CrossrefPubMedGoogle Scholar
  • 20 Ueda R, Shimizu-Motohashi Y, Sugai K. et al. Seizure imitators monitored using video-EEG in children with intellectual disabilities. Epilepsy Behav 2018; 84: 122-126
    CrossrefPubMedGoogle Scholar
  • 21 Morin CM, LeBlanc M, Daley M, Gregoire JP, Mérette C. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med 2006; 7 (02) 123-130
    CrossrefPubMedGoogle Scholar
  • 22 Hylkema T, Vlaskamp C. Significant improvement in sleep in people with intellectual disabilities living in residential settings by non-pharmaceutical interventions. J Intellect Disabil Res 2009; 53 (08) 695-703
    CrossrefPubMedGoogle Scholar
  • 23 Morin CM, Benca R. Chronic insomnia. Lancet 2012; 379 (9821): 1129-1141
    CrossrefPubMedGoogle Scholar
  • 24 ICSD-3, Sleep Disorder Breathing. International Classification of Sleep Disorders: Diagnostic and Coding Manuel, Revised. 3 rd ed.. Darien, IL: American Academy of Sleep Medicine; 2014: 53-68
    Google Scholar
  • 25 Dayyat EA, Spruyt K, Molfese DL, Gozal D. Sleep estimates in children: parental versus actigraphic assessments. Nat Sci Sleep 2011; 3: 115-123
    PubMedGoogle Scholar