Chen Jing, Su Wei, Gao Dan, Liu Fangfang, Chen Shuang, Zhang Wenhan, Peng Min, Lei Tao, Zhu Hongmin
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chigene (Beijing) Translational Medical Research Center Co., Ltd., Beijing, China.
Front Genet. 2025 Aug 6;16:1591551. doi: 10.3389/fgene.2025.1591551. eCollection 2025.
Cockayne syndrome (CS), a rare hereditary neurodegenerative disorder caused by pathogenic variants in (CSB) and (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.
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-III).
All patients (6 males, 2 females) presented with early-onset motor delay and spasticity, initially misdiagnosed as CP. Genetic testing identified pathogenic variants, including exon deletions (Exon4; Exon6-12), a nonsense (c.856A>T), frameshift (c.394_398del), and splice-site (c.618-2A>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.
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.
科凯恩综合征（CS）是一种由（CSB）和（CSA）基因的致病变异引起的罕见遗传性神经退行性疾病，在临床上常与脑瘫（CP）重叠，导致误诊。本研究评估基因检测在鉴别诊断中的作用，将肝功能障碍作为疾病严重程度的生物标志物进行研究，并描述与CSA相关的CS的临床特征。
对8例与CSA相关的CS患者进行回顾性病例系列研究。分析临床数据、神经影像学、基因图谱和肝功能。根据既定的CS亚型（I - III）对疾病严重程度进行分类。
所有患者（6例男性，2例女性）均表现为早发性运动发育迟缓及痉挛，最初被误诊为CP。基因检测发现了致病变异，包括外显子缺失（外显子4；外显子6 - 12）、无义突变（c.856A>T）、移码突变（c.394_398del）和剪接位点突变（c.618 - 2A>G），证实为常染色体隐性遗传（复合杂合子/纯合子）。亚型分布包括CS I（n = 5）、CS II（n = 2）和CS III（n = 1）。CS II型病例诊断较早，具有典型的CS特征。肝功能障碍与疾病严重程度相关，并随病情进展而恶化。所有患者均出现跟腱挛缩；与未接受康复治疗的病例（n = 3）相比，接受系统康复治疗的患者（n = 5）跟腱挛缩严重程度明显减轻。2例患者出现无汗症，这是一种罕见报道的皮肤表现。
基因检测对于鉴别与CSA相关的CS和CP至关重要。肝功能障碍可作为疾病进展的生物标志物，需要进行常规监测。康复治疗可减轻跟腱挛缩，凸显了其临床价值。本研究通过将无汗症确定为一种罕见报道的特征，扩展了与CSA相关的CS的表型谱，为诊断和管理提供了见解。
