Department of Pediatrics, Tokyo Children's Rehabilitation Hospital, 4-10-1 Gakuen, Musashi-Murayama, Tokyo, 208-0011, Japan.
Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, 187-8551, Japan.
BMC Med Genomics. 2023 Mar 6;16(1):43. doi: 10.1186/s12920-023-01465-3.
X-linked methyl-CpG-binding protein 2 (MECP2) duplication syndrome is prevalent in approximately 1% of X-linked intellectual disabilities. Accumulating evidence has suggested that MECP2 is the causative gene of MECP2 duplication syndrome. We report a case of a 17-year-old boy with a 1.2 Mb duplication distal to MECP2 on chromosome Xq28. Although this region does not contain MECP2, the clinical features and course of the boy are remarkably similar to those observed in MECP2 duplication syndrome. Recently, case reports have described duplication in the region distal to, and not containing, MECP2. These regions have been classified as the K/L-mediated Xq28 duplication region and int22h1/int22h2-mediated Xq28 duplication region. The case reports also described signs similar to those of MECP2 duplication syndrome. To the best of our knowledge, ours is the first case to include these two regions.
The boy presented with a mild to moderate regressive intellectual disability and progressive neurological disorder. He developed epilepsy at the age of 6 years and underwent a bilateral equinus foot surgery at 14 years of age because of the increasing spasticity in lower extremities since the age of 11. Intracranial findings showed hypoplasia of the corpus callosum, cerebellum, and brain stem; linear hyperintensity in the deep white matter; and decreased white matter capacity. During his childhood, he suffered from recurrent infection. However, genital problems, skin abnormalities and gastrointestinal manifestations (gastroesophageal reflux) were not observed.
Cases in which duplication was observed in the region of Xq28 that does not include MECP2 also showed symptoms similar to those of MECP2 duplication syndrome. We compared four pathologies: MECP2 duplication syndrome with minimal regions, duplication within the two distal regions without MECP2, and our case including both regions. Our results suggest that MECP2 alone may not explain all symptoms of duplication in the distal part of Xq28.
X 连锁甲基化CpG 结合蛋白 2（MECP2）重复综合征在大约 1%的 X 连锁智力障碍中较为常见。越来越多的证据表明，MECP2 是 MECP2 重复综合征的致病基因。我们报告了一例 17 岁男孩，其 X 染色体 Xq28 上 MECP2 远端有 1.2 Mb 的重复。尽管该区域不包含 MECP2，但该男孩的临床特征和病程与 MECP2 重复综合征非常相似。最近，病例报告描述了 MECP2 远端不包含 MECP2 的区域的重复。这些区域被归类为 K/L 介导的 Xq28 重复区域和 int22h1/int22h2 介导的 Xq28 重复区域。病例报告还描述了与 MECP2 重复综合征相似的体征。据我们所知，这是首例包含这两个区域的病例。
该男孩表现为轻度至中度进行性智力障碍和进行性神经功能障碍。他在 6 岁时出现癫痫，并在 14 岁时因 11 岁以来下肢痉挛性增加而接受双侧马蹄内翻足手术。颅内发现胼胝体、小脑和脑干发育不良；深部白质线性高信号；白质容量减少。在他的童年时期，他经常反复感染。然而，没有观察到生殖器问题、皮肤异常和胃肠道表现（胃食管反流）。
在不包含 MECP2 的 Xq28 区域观察到重复的病例也表现出与 MECP2 重复综合征相似的症状。我们比较了四种病理学：最小区域的 MECP2 重复综合征、不包含 MECP2 的两个远端区域内的重复、以及包括两个区域的我们的病例。我们的结果表明，MECP2 本身可能无法解释 Xq28 远端重复的所有症状。
