Division of Child Neuropsychiatry, Department of Neuroscience, University of Rome Tor Vergata, 00133 Rome, Italy.
Department of Child Neuropsychiatry, USL Umbria 2, 05100 Terni, Italy.
Int J Environ Res Public Health. 2019 Aug 23;16(17):3075. doi: 10.3390/ijerph16173075.
Rett syndrome (RTT) is a neurodevelopmental disorder with a genetic basis that is associated with the mutation of the X-linked methyl-CpG binding protein 2 (MECP2) gene in approximately 90% of patients. RTT is characterized by a brief period of normal development followed by loss of acquired skills and evolution towards impairment of brain and motor functions and multi-organ dysfunction. Originally, RTT was considered lethal in males as it has an X-linked dominant inheritance. However, although this syndrome has a higher incidence in females, rare cases are also documented in males. Here, we describe the case of an 11-year-old male patient with a microduplication MECP2 Xq28. Our patient is currently living, while his older brother with the same mutation died at the age of 9 years. We showed that the role of MECP2 as an epigenetic modulator and the X-chromosome inactivation pattern can explain the lethal clinical form of the older brother with the same microduplication MECP2 Xq28 presented by our patient who is still alive. Given the limited case history of RTT in males, further studies are needed to better characterize this syndrome in males and consequently improve the currently available therapeutic strategies.
雷特综合征（RTT）是一种神经发育障碍，具有遗传基础，约 90%的患者与 X 连锁甲基化CpG 结合蛋白 2（MECP2）基因突变有关。RTT 的特征是短暂的正常发育期，随后丧失获得的技能，并逐渐发展为大脑和运动功能受损以及多器官功能障碍。最初，由于 RTT 具有 X 连锁显性遗传，男性患者被认为是致命的。然而，尽管这种综合征在女性中的发病率更高，但也有罕见的男性病例记录。在这里，我们描述了一例 11 岁男性患者，其 MECP2 Xq28 存在微重复。我们的患者目前仍存活，而具有相同突变的哥哥在 9 岁时死亡。我们表明，MECP2 作为表观遗传调节剂的作用以及 X 染色体失活模式可以解释我们的患者所呈现的相同 MECP2 Xq28 微重复的具有致命临床形式的哥哥的致死临床形式。鉴于男性 RTT 的病史有限，需要进一步的研究来更好地描述男性中的这种综合征，并最终改进目前可用的治疗策略。
