{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:42:01Z","timestamp":1791013321774,"version":"4.1.0"},"reference-count":19,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Rett syndrome (RS) is a rare neurodevelopmental disorder primarily affecting females, characterized by severe neurological impairment and complex comorbidities, including epilepsy, scoliosis, and respiratory dysfunction. Respiratory complications, such as recurrent infections and sleep-disordered breathing (SDB), are increasingly recognized as significant contributors to morbidity. This study aimed to evaluate the prevalence, severity, and management of major comorbidities\u2014including epilepsy, scoliosis, respiratory infections, and SDB\u2014in a pediatric cohort with genetically confirmed RS. Methods: We conducted a retrospective review of medical records from 23 female patients under 18 years of age with MECP2 mutations, referred to our tertiary care center from 2021 to 2025. Data on epilepsy, scoliosis, respiratory infections, and nutritional status were collected. The presence of SDB was assessed through overnight home polygraphy (oPG) and transcutaneous carbon dioxide monitoring in selected cases. Results: Epilepsy affected 65% of patients, all with good seizure control. Scoliosis was present in 52%, with two patients requiring spinal surgery. At least one episode of lower respiratory tract infection (LRTI) was presented in 39% of our girls. LRTIs positively correlated with the number of hospitalization and antibiotic treatment. Among patients undergoing oPG, 67% presented obstructive sleep apnea, with its severity positively correlating with the frequency of lower respiratory infections. Severe nocturnal hypercapnia was documented in three patients, leading to non-invasive or invasive ventilation. Conclusions: Our findings highlight the high prevalence of sleep-related respiratory disorders and their association with respiratory infections in children with RS. Systematic respiratory assessment, including sleep studies, and early implementation of airway clearance techniques and ventilatory support are crucial to improving clinical outcomes in this vulnerable population.<\/jats:p>","DOI":"10.3390\/children12091181","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T08:08:46Z","timestamp":1756973326000},"page":"1181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Managing Complexity in Rett Syndrome with a Focus on Respiratory Involvement: A Tertiary Center Experience"],"prefix":"10.3390","volume":"12","author":[{"given":"Adele","family":"Corcione","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Antonio","family":"Del Giudice","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Basilicata","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariantonia","family":"Maglio","sequence":"additional","affiliation":[{"name":"European Laboratory for the Investigation of Food-Induced Diseases, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Aiello","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Child and Adolescents Neuropsychiatry, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2239-5776","authenticated-orcid":false,"given":"Raffaele","family":"Cerchione","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-3545","authenticated-orcid":false,"given":"Anna","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Respiratory Physiopathology and Rehabilitation Unit, AORN dei Colli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Amaddeo","sequence":"additional","affiliation":[{"name":"Emergency Department, IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7282-6018","authenticated-orcid":false,"given":"Melissa","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","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_2","unstructured":"Asuncion, R.M.D., and Ramani, P.K. (2025). Rett Syndrome. StatPearls, StatPearls Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vilvarajan, S., McDonald, M., Douglas, L., Newham, J., Kirkland, R., Tzannes, G., Tay, D., Christodoulou, J., Thompson, S., and Ellaway, C. (2023). Multidisciplinary Management of Rett Syndrome: Twenty Years\u2019 Experience. Genes, 14.","DOI":"10.3390\/genes14081607"},{"key":"ref_4","unstructured":"Writing Group For Practice Guidelines For Diagnosis And Treatment Of Genetic Diseases Medical Genetics Branch Of Chinese Medical Association, Guan, R., Li, Q., and Fu, S. (2020). Clinical practice guidelines for Rett syndrome. Chin. J. Med. Genet., 37, 308\u2013312. (In Chinese)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1002\/ppul.27030","article-title":"Management of respiratory issues in patients with Rett syndrome: Italian experts\u2019 consensus using a Delphi approach","volume":"59","author":"Cherchi","year":"2024","journal-title":"Pediatr Pulmonol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"NP118","DOI":"10.1177\/0883073813508313","article-title":"Severe respiratory dysrhythmia in Rett syndrome treated with topiramate","volume":"29","author":"Krajnc","year":"2014","journal-title":"J. Child Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"597","DOI":"10.5664\/jcsm.2172","article-title":"Rules for scoring respiratory events in sleep: Update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine","volume":"8","author":"Berry","year":"2012","journal-title":"J. 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