SLC33A1突变所致常染色体隐性铜代谢障碍中的耐药性癫痫

文献信息

中文摘要

未标注： SLC33A1突变（Huppke-Brendel综合征）是一种与铜代谢相关的罕见常染色体隐性遗传病，其特征为全面性发育迟缓、感音神经性听力损失、先天性白内障和全身性肌张力低下。我们报告了两名6岁以下、携带新发SLC33A1基因突变的同胞，其父母为杂合子。第一名患者因该新发基因突变而出现早发性耐药性癫痫（DRE）；第二名患者未出现癫痫发作，但具有该综合征的其他若干表型特征，突显了癫痫外显率的家族内变异。在第一名DRE患者的脑电图上，可见颞顶区独立的尖慢波放电，并伴有全面性背景减慢。弥漫性电衰减伴叠加的阵发性快活动与癫痫发作症状学相关。神经影像学显示全面性脑和小脑萎缩、代偿性脑室扩大以及双侧慢性硬膜下积液。我们描述了两名同胞共有的基因突变，并强调其重叠和不同的临床特征、管理挑战以及有创神经调控的并发症。这些病例扩展了铜相关代谢紊乱的鉴别诊断。
实践意义： SLC33A1相关疾病中癫痫外显率的可变性可表现为癫痫表型。

英文摘要

UNLABELLED: SLC33A1 mutation (Huppke-Brendel Syndrome) is a rare, autosomal recessive disorder associated with copper metabolism and characterized by global developmental delay, sensorineural hearing loss, congenital cataract and generalized hypotonia. We report two siblings under 6 years with novel SLC33A1 gene mutation, born from heterozygous parents. The first patient developed early onset drug-resistant epilepsy (DRE) secondary to the novel genetic mutation; the second patient did not develop seizures but shared several other phenotypic features of the syndrome, highlighting intrafamilial variation in seizure penetrance. On electroencephalography of the first patient with DRE, independent spike and wave discharges were noted in the temporoparietal region with generalized background slowing. Diffuse electrodecrement with overriding paroxysmal fast activity was correlated with seizure semiology. Neuroimaging revealed generalized cerebral and cerebellar atrophy, ex-vacuo ventriculomegaly, and bilateral chronic subdural collections. We describe a shared genetic mutation in two siblings and highlight their overlapping and distinct clinical features, management challenges, and complications with invasive neuromodulation. These cases expand the differential diagnosis of copper-related metabolic disorders.
PRACTICAL IMPLICATIONS: Variable seizure penetrance in SLC33A1 related disorders could manifest as epileptic phenotypes.