Sex-dependent clinical divergence in adult-onset CLN6-Batten disease: a case study of a Chinese brother–sister pair

作者：Shu-Ya Liu, Shih‐Jen Tsai, Mu‐N Liu · 发表于：Neurocase · 年份：2026 · DOI：10.1080/13554794.2026.2704842 · 研究领域：Lysosomal Storage Disorders Research、Glycogen Storage Diseases and Myoclonus、Trypanosoma species research and implications

Neuronal ceroid lipofuscinoses (NCLs) are rare, genetically heterogeneous neurodegenerative disorders involving progressive cognitive, motor, and psychiatric decline. Adult-onset CLN6 disease (Kufs type) is extremely uncommon, typically emerging after age 30 with seizures, ataxia, and gradual functional deterioration. We report a Chinese brother - sister pair carrying identical compound heterozygous CLN6 mutations (c.307C >T [p.Arg103Trp] and c.425A >G [p.Tyr142Cys]) who exhibited marked intrafamilial phenotypic divergence. The younger sister developed generalized seizures at age 30, followed by focal seizures, gait instability, and progressive ataxia, but remained partially mobile and free of psychiatric symptoms for more than 10 years. By contrast, her older brother developed seizures at age 35 and prominent psychosis at age 42, including persecutory delusions and hallucinations, followed by rapid neurological deterioration and complete dependence within 2 years. This sibship illustrates substantial clinical heterogeneity despite an identical CLN6 genotype. Rather than establishing a causal effect of sex, this report suggests that sex may modify disease expression in adult-onset CLN6 and that prominent psychiatric manifestations may signal a more aggressive clinical trajectory.