Minerva Michele, Perilli Lorenzo, Carbone Samanta, Rossi Margherita Maria, Lotti Federica, Lonoce Luisa, Curcio Maria Rosaria, Grosso Salvatore
Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
Neurol Int. 2025 Jan 20;17(1):14. doi: 10.3390/neurolint17010014.
BACKGROUND/OBJECTIVES: ZNF711(Zinc finger protein 711) encodes a zinc finger protein of currently undefined function, located on the X chromosome. Current knowledge includes a limited number of case reports where this gene has been exclusively associated with X-linked intellectual disability (XLID). As far as we are aware, we report the first cases of epilepsy associated with this particular variant. Our aim is to further delineate the phenotypic spectrum of ZNF711 gene pathogenic variants, adding clinical features to this rare condition, following a genotype-first approach.
We describe the familiar case of two male siblings presenting with moderate intellectual disability (ID), language delay, and motor stereotypies. Additionally, they experienced generalized tonic-clonic seizures (GTCSs) and myoclonic seizures with interictal electroencephalographic abnormalities. Both children underwent various genetic testing and counselling, including an extended next-generation sequencing (NGS) panel, revealing a hemizygous c.657C > G pathogenic variant in the ZNF711 gene from maternal inheritance.
This case expands the clinical range of ZNF711 variants by highlighting epilepsy as a potential comorbidity and suggesting other possible causal candidates for generalized epilepsy. Moreover, it emphasizes the need for further research into the phenotypic spectrum associated with this variant.
背景/目的：ZNF711（锌指蛋白711）编码一种功能目前尚不清楚的锌指蛋白，位于X染色体上。目前已知的情况包括有限数量的病例报告，其中该基因仅与X连锁智力障碍（XLID）相关。据我们所知，我们报告了首例与这种特定变异相关的癫痫病例。我们的目的是采用先基因型的方法，进一步描绘ZNF711基因致病变异的表型谱，为这种罕见疾病增加临床特征。
我们描述了一个家族病例，两名男性同胞表现为中度智力障碍（ID）、语言发育迟缓及运动刻板行为。此外，他们还经历了全身强直阵挛发作（GTCSs）和肌阵挛发作，发作间期脑电图异常。两个孩子都接受了各种基因检测和咨询，包括扩展的下一代测序（NGS） panel，结果显示来自母亲遗传的ZNF711基因存在半合子c.657C > G致病变异。
本病例通过强调癫痫作为一种潜在的合并症，并提示全身性癫痫的其他可能病因，扩大了ZNF711变异的临床范围。此外，它强调了对与这种变异相关的表型谱进行进一步研究的必要性。
