{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:40:57Z","timestamp":1784734857925,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Individuals with Rett Syndrome (RTT), a rare neurodevelopmental disorder, present disordered breathing during wakefulness. Whilst findings on breathing during sleep are contradictory, the relation between sleep breathing and their clinical features, genetic characteristics, age, and sleep phase is rarely investigated, which is the objective of this study. Overnight polysomnography (PSG) was performed. Sleep macrostructure parameters were compared between the RTT subjects with and without sleep-disordered breathing (SDB). The association between the apnea\u2013hypopnea index (AHI) with age at PSG was tested. Particularly for RTT subjects with SDB, the respiratory indexes in REM and NREM sleep were compared. Stratified analyses per clinical characteristics, genetic characteristics, and clinical features\u2019 severity were performed. Non-parametric statistics were applied. A sample of 11 female RTT subjects, aged 8.69 \u00b1 5.29 years with ten confirmed with MECP2 mutations, were studied. The average AHI was 3.94 \u00b1 1.19\/h TST, of which eight (72.73%) had obstructive sleep apnea, i.e., six in 1\/h TST \u2264 AHI \u2264 5\/h TST, and two in AHI &gt; 5\/h TST. The mean SpO2% was 81.00 \u00b1 35.15%. The AHI was not significantly correlated with their age at PSG (rs = \u22120.15, p = 0.67). Sleep macrostructure in SDB-absent and SDB-present groups was not different. Respiratory indexes in those with obstructive sleep apnea showed no difference between REM and NREM sleep nor any of the strata. In our clinical sample, more than half of the RTT subjects with MECP2 mutations had obstructive sleep apnea in both NREM and REM sleep which was unrelated to their clinical features. Our results also indicated hypoxemia throughout nocturnal sleep in RTT. To conclude, our results suggest that disordered breathing during sleep is prevalently present in RTT as an independent clinical feature.<\/jats:p>","DOI":"10.3390\/ijerph192013082","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T05:31:18Z","timestamp":1665552678000},"page":"13082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sleep Respiratory Disturbances in Girls with Rett Syndrome"],"prefix":"10.3390","volume":"19","author":[{"given":"Xinyan","family":"Zhang","sequence":"first","affiliation":[{"name":"NeuroDiderot-INSERM, Universit\u00e9 de Paris, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-9402","authenticated-orcid":false,"given":"Marcel","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Sleep-Wake Disorders and Chronobiology, Hospital Gelderse Vallei Ede, Governor Kremers Centre, Maastricht University Medical Centre, 6716 RP Gelderland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopold","family":"Curfs","sequence":"additional","affiliation":[{"name":"Governor Kremers Centre, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2914-9074","authenticated-orcid":false,"given":"Karen","family":"Spruyt","sequence":"additional","affiliation":[{"name":"NeuroDiderot-INSERM, Universit\u00e9 de Paris, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett syndrome: Revised diagnostic criteria and nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/humu.23263","article-title":"RettBASE: Rett syndrome database update","volume":"38","author":"Krishnaraj","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neubiorev.2019.05.013","article-title":"Rett syndrome before regression: A time window of overlooked opportunities for diagnosis and intervention","volume":"107","author":"Cosentino","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1053\/ejpn.2002.0612","article-title":"An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett Syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001","volume":"6","author":"Hagberg","year":"2002","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1152\/physiol.00008.2020","article-title":"The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions","volume":"35","author":"Ramirez","year":"2020","journal-title":"Physiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/adc.85.1.29","article-title":"Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder","volume":"85","author":"Julu","year":"2001","journal-title":"Arch. Dis. Child."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/S0140-6736(08)60849-1","article-title":"Cardiorespiratory challenges in Rett\u2019s syndrome","volume":"371","author":"Julu","year":"2008","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.resp.2013.06.022","article-title":"Breathing challenges in Rett Syndrome: Lessons learned from humans and animal models","volume":"189","author":"Ramirez","year":"2013","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.braindev.2018.03.010","article-title":"The course of awake breathing disturbances across the lifespan in Rett syndrome","volume":"40","author":"Tarquinio","year":"2018","journal-title":"Brain Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/j.braindev.2005.02.012","article-title":"Assessment of the maturity-related brainstem functions reveals the heterogeneous phenotypes and facilitates clinical management of Rett syndrome","volume":"27","author":"Julu","year":"2005","journal-title":"Brain Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.pediatrneurol.2007.06.009","article-title":"Disturbances in cardiorespiratory function during day and night in Rett syndrome","volume":"37","author":"Rohdin","year":"2007","journal-title":"Pediatr. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0022-3476(94)70196-2","article-title":"Polysomnographic characteristics of patients with Rett syndrome","volume":"125","author":"Marcus","year":"1994","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/ana.410210410","article-title":"Rett\u2019s syndrome: Characterization of respiratory patterns and sleep","volume":"21","author":"Glaze","year":"1987","journal-title":"Ann. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.5664\/jcsm.7974","article-title":"Sleep-Disordered Breathing in Pediatric Patients With Rett Syndrome","volume":"15","author":"Sarber","year":"2019","journal-title":"J. Clin. Sleep Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1177\/0883073811429859","article-title":"Respiratory disturbances in rett syndrome: Don\u2019t forget to evaluate upper airway obstruction","volume":"27","author":"Hagebeuk","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1177\/0883073816671439","article-title":"Sleep Apnea in Patients With Rett Syndrome: Roles for Polysomnography and Adenotonsillectomy","volume":"31","author":"Bassett","year":"2016","journal-title":"J. Child Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/j.1469-8749.2012.04432.x","article-title":"Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene","volume":"55","author":"Hagebeuk","year":"2012","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejpn.2018.09.003","article-title":"Polysomnographic findings in Rett syndrome","volume":"23","author":"Amaddeo","year":"2019","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11325-012-0654-x","article-title":"Polysomnographic findings in Rett syndrome: A case-control study","volume":"17","author":"Carotenuto","year":"2013","journal-title":"Sleep Breath"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, X.Y., and Spruyt, K. (2022). Literature Cases Summarized Based on Their Polysomnographic Findings in Rett Syndrome. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19063422"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, X.Y., and Spruyt, K. (2022). A meta-review of standard polysomnography parameters in Rett Syndrome. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.963626"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/sleep\/32.6.731","article-title":"Sleep Disordered Breathing in Children in a General Population Sample: Prevalence and Risk Factors","volume":"32","author":"Bixler","year":"2009","journal-title":"Sleep"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1164\/ajrccm.164.1.2008171","article-title":"Sleep-disordered breathing in children","volume":"164","author":"Marcus","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1365-2869.2009.00760.x","article-title":"Sleep state distribution of obstructive events in children: Is obstructive sleep apnoea really a rapid eye movement sleep-related condition?","volume":"18","author":"Verginis","year":"2009","journal-title":"J. Sleep Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.sleep.2011.10.025","article-title":"REM and NREM sleep-state distribution of respiratory events in habitually snoring school-aged community children","volume":"13","author":"Spruyt","year":"2012","journal-title":"Sleep Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/jsr.12512","article-title":"CDKL5 deficiency entails sleep apneas in mice","volume":"26","author":"Alvente","year":"2017","journal-title":"J. Sleep Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ammanuel, S., Chan, W.C., Adler, D.A., Lakshamanan, B.M., Gupta, S.S., Ewen, J.B., Johnston, M.V., Marcus, C.L., Naidu, S., and Kadam, S.D. (2015). Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138113"},{"key":"ref_29","unstructured":"Iber, C., Ancoli-Israel, S., Chesson, A.L., and Quan, S.F. (2007). The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications, American Academy of Sleep Medicine."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e022427","DOI":"10.1161\/JAHA.121.022427","article-title":"Sleep-Disordered Breathing and Cardiovascular Disease in Children and Adolescents: A Scientific Statement From the American Heart Association","volume":"10","author":"Isaiah","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17230","DOI":"10.1523\/JNEUROSCI.2951-12.2012","article-title":"Anxiety-Related Mechanisms of Respiratory Dysfunction in a Mouse Model of Rett Syndrome","volume":"32","author":"Ren","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fuchs, C., Gennaccaro, L., Trazzi, S., Bastianini, S., Bettini, S., Lo Martire, V., Ren, E., Medici, G., Zoccoli, G., and Rimondini, R. (2018). Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder. Neural Plast., 2018.","DOI":"10.1155\/2018\/9726950"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ward, C.S., Huang, T.-W., Herrera, J.A., Samaco, R.C., McGraw, C.M., Parra, D.E., Arvide, E.M., Ito-Ishida, A., Meng, X., and Ure, K. (2020). Loss of MeCP2 Function Across Several Neuronal Populations Impairs Breathing Response to Acute Hypoxia. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.593554"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/ppul.20866","article-title":"Autonomic dysregulation in young girls with Rett Syndrome during nighttime in-home recordings","volume":"43","author":"Lieske","year":"2008","journal-title":"Pediatr. Pulmonol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e13616","DOI":"10.1111\/jsr.13616","article-title":"Obstructive sleep apnea: Transition from pathophysiology to an integrative disease model","volume":"31","author":"McNicholas","year":"2022","journal-title":"J. Sleep Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1177\/0003489417723033","article-title":"Dysphagia in Rett Syndrome: A Descriptive Study","volume":"126","author":"Mezzedimi","year":"2017","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1097\/MCP.0000000000000623","article-title":"A contemporary review of obstructive sleep apnea","volume":"25","author":"Ralls","year":"2019","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1002\/ajmg.a.37784","article-title":"Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype","volume":"170","author":"Boban","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/jsr.12240","article-title":"The trajectories of sleep disturbances in Rett syndrome","volume":"24","author":"Wong","year":"2015","journal-title":"J. Sleep Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.braindev.2007.04.001","article-title":"Sleep problems in Rett syndrome","volume":"29","author":"Young","year":"2007","journal-title":"Brain Dev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/jnr.24730","article-title":"Sleep problems in Rett syndrome animal models: A systematic review","volume":"99","author":"Zhang","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1152\/jappl.1996.81.6.2651","article-title":"Arousal pattern following central and obstructive breathing abnormalities in infants and children","volume":"81","author":"McNamara","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.5664\/jcsm.6868","article-title":"Sleep Architecture in Children With Common Phenotype of Obstructive Sleep Apnea","volume":"14","author":"Durdik","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1164\/ajrccm.162.2.9908058","article-title":"Sleep architecture and respiratory disturbances in children with obstructive sleep apnea","volume":"162","author":"Goh","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S0022-3476(94)70007-9","article-title":"Determinants of growth in children with the obstructive sleep apnea syndrome","volume":"125","author":"Marcus","year":"1994","journal-title":"J. Pediatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"777","DOI":"10.5664\/jcsm.6614","article-title":"Sleep Complaints and Sleep Architecture in Children With Idiopathic Central Sleep Apnea","volume":"13","author":"Gurbani","year":"2017","journal-title":"J. Clin. Sleep Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.prrv.2009.10.003","article-title":"Sleep, sleep disordered breathing, and nocturnal hypoventilation in children with neuromuscular diseases","volume":"11","author":"Arens","year":"2010","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_48","unstructured":"Bajaj, L., Hambidge, S.J., Kerby, G., and Nyquist, A.-C. (2011). Sleep disordered breathing in children. Berman\u2019s Pediatric Decision Making, Mosby. [5th ed.]."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"519","DOI":"10.5664\/jcsm.27651","article-title":"Marked reduction in obstructive sleep apnea severity in slow wave sleep","volume":"5","author":"Ratnavadivel","year":"2009","journal-title":"J. Clin. Sleep Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.sleep.2005.10.006","article-title":"Half of patients with obstructive sleep apnea have a higher NREM AHI than REM AHI","volume":"7","author":"Siddiqui","year":"2006","journal-title":"Sleep Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.jsmc.2012.06.011","article-title":"Respiratory Physiology During Sleep","volume":"7","author":"Malik","year":"2012","journal-title":"Sleep Med. Clin."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11521","DOI":"10.1523\/JNEUROSCI.4373-05.2005","article-title":"Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice","volume":"25","author":"Viemari","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1113\/jphysiol.2006.119966","article-title":"Breathing dysfunctions associated with impaired control of postinspiratory activity in Mecp2-\/y knockout mice","volume":"579","author":"Stettner","year":"2007","journal-title":"J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.conb.2017.03.021","article-title":"Wake-sleep circuitry: An overview","volume":"44","author":"Saper","year":"2017","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.molmed.2003.10.010","article-title":"Serotonin receptors: Guardians of stable breathing","volume":"9","author":"Richter","year":"2003","journal-title":"Trends Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.resp.2009.04.017","article-title":"Breathing disorders in Rett syndrome: Progressive neurochemical dysfunction in the respiratory network after birth","volume":"168","author":"Katz","year":"2009","journal-title":"Respir Physiol. Neurobiol."},{"key":"ref_57","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age With Human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neulet.2005.05.056","article-title":"Defect in normal developmental increase of the brain biogenic amine concentrations in the mecp2-null mouse","volume":"386","author":"Ide","year":"2005","journal-title":"Neurosci. Lett."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/20\/13082\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:17Z","timestamp":1760143817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/20\/13082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":58,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijerph192013082"],"URL":"https:\/\/doi.org\/10.3390\/ijerph192013082","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}