De Luisa Angelica, Cesaroni Carlo A, Pollazzon Marzia, Spagnoli Carlotta, Caraffi Stefano G, Leon Alberta, Rizzi Susanna, Frattini Daniele, Cavalli Anna, Garavelli Livia, Fusco Carlo
Child Neurology and Psychiatry Unit, Pediatric Neurophysiology Laboratory, Mother and Child Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Medical Genetics Unit, Mother and Child Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Neuropediatrics. 2025 Feb;56(1):56-60. doi: 10.1055/a-2447-1508. Epub 2024 Nov 14.
Pathogenic variants in the gene are often dominant-negative and cause an X-linked form of Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features. However, rare variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Here we describe an 11-year-old girl with epilepsy, walking disorder, and neurodevelopmental disorder. A neurophysiological examination of nerve conduction velocity showed a mixed, sensory-motor, chronic 4-limb polyneuropathy. Whole-exome sequencing identified the variant c.3145C > T p.(Arg1049*) in (NM_006306.3), which can be classified as pathogenic. To the best of our knowledge, among 79 individuals with -related DEE reported in the literature, altered peripheral nerve conduction has never been described. In this article, we propose that severe sensory-motor polyneuropathy could be an expansion of the -related phenotype.
该基因中的致病变异通常为显性负性，可导致一种X连锁型的科妮莉亚·德·朗格综合征（CdLS），伴有生长发育迟缓及典型的面部特征。然而，罕见的变异会引发一种伴有难治性早发性癫痫的发育性和癫痫性脑病（DEE），而CdLS中不存在这种情况。本文描述了一名患有癫痫、行走障碍和神经发育障碍的11岁女孩。神经传导速度的神经生理学检查显示为混合性、感觉运动性、慢性四肢多发性神经病。全外显子组测序在该基因（NM_006306.3）中鉴定出变异c.3145C＞T p.(Arg1049*)，该变异可被分类为致病性变异。据我们所知，在文献报道的79例与该基因相关的DEE患者中，从未描述过外周神经传导改变的情况。在本文中，我们提出严重的感觉运动性多发性神经病可能是该基因相关表型的一种扩展。
