{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:28:08Z","timestamp":1790843288148,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Cockayne syndrome (CS), a rare hereditary neurodegenerative disorder caused by pathogenic variants in <jats:italic>ERCC6<\/jats:italic> (CSB) and <jats:italic>ERCC8<\/jats:italic> (CSA), often clinically overlaps with cerebral palsy (CP), leading to misdiagnosis. This study evaluates the role of genetic testing in differential diagnosis, examines hepatic dysfunction as a biomarker of disease severity, and delineates clinical characteristics of CSA-related CS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective case series of eight CSA-related CS patients was conducted. Clinical data, neuroimaging, genetic profiles, and hepatic function were analyzed. Disease severity was classified according to established CS subtypes (I\u2013III).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients (6 males, 2 females) presented with early-onset motor delay and spasticity, initially misdiagnosed as CP. Genetic testing identified pathogenic <jats:italic>ERCC8<\/jats:italic> variants, including exon deletions (Exon4; Exon6-12), a nonsense (c.856A&amp;gt;T), frameshift (c.394_398del), and splice-site (c.618-2A&amp;gt;G) variant, confirming autosomal recessive inheritance (compound heterozygous\/homozygous). Subtype distribution included CS I (n = 5), CS II (n = 2), and CS III (n = 1). CS II cases exhibited earlier diagnosis and classic CS features. Hepatic dysfunction correlated with disease severity, worsening with progression. Achilles tendon contractures developed in all patients; systematic rehabilitation (n = 5) significantly reduced contracture severity compared to non-rehabilitated cases (n = 3). Two patients displayed anhidrosis, a rarely reported dermatological manifestation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic testing is essential to differentiate CSA-related CS from CP. Hepatic dysfunction serves as a biomarker for disease progression, warranting routine monitoring. Rehabilitation therapy mitigates Achilles tendon contractures, underscoring its clinical value. This study expands the phenotypic spectrum of CSA-related CS by identifying anhidrosis as a rarely reported feature, providing insights for diagnosis and management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1591551","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T04:11:55Z","timestamp":1754453515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical and genetic analysis of ERCC8-Related cockayne syndrome: hepatic dysfunction as a biomarker, anhidrosis as a rare feature, and rehabilitation outcomes for ankle contractures"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e20200622","DOI":"10.1084\/jem.20200622","article-title":"ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients","volume":"218","author":"Apelt","year":"2021","journal-title":"J. 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