Aslam Hira, Balasubramaniam Seema, McDunnah Paige, Harrison Meghan
Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
Nemours Children's Health, Wilmington, DE.
J Dev Behav Pediatr. 2025 May 15;46(4):e397-e401. doi: 10.1097/DBP.0000000000001374.
The purpose of this study was to explore the genotypic and phenotypic presentation of males with MECP2 -related neurodevelopmental disorders. When variants in the MECP2 gene are discovered in patients, Rett syndrome becomes a possible diagnosis. Rett syndrome, however, does not encapsulate all phenotypic variations in MECP2 gene mutations, and specific diagnosis can become tricky especially in the male population as mutations in the gene were historically thought to affect females only. The authors present a rare case of a male with a previously unpublished genetic variant resulting in a distinct clinical presentation not meeting the criteria for typical or atypical Rett syndrome.
This patient's institutional electronic medical record was accessed, and information was reviewed.
It was discovered that this patient had a maternally inherited variant in his MECP2 gene, resulting in a unique and previously undescribed form of MECP2 -related neurodevelopmental disorder, presenting with language regression followed by speech apraxia and motor discoordination.
DISCUSSION/CONCLUSION: Literature reports on various phenotypes associated with MECP2 gene mutations and elaborates on previously identified forms of typical and atypical Rett syndrome. Through this case report, the authors uncovered a pathogenic variant in MECP2 resulting in a rare phenotype of MECP2 -related neurodevelopmental disorder that has not previously been described. This should encourage clinicians to think more broadly when approaching diagnosis of children with developmental differences. This also reinforces that Rett syndrome or MECP2 mutations can often present on a spectrum, and it may be beneficial to modify diagnostic criteria to reflect this.
本研究旨在探索患有与MECP2相关的神经发育障碍的男性的基因型和表型表现。当在患者中发现MECP2基因变异时，雷特综合征成为一种可能的诊断。然而，雷特综合征并未涵盖MECP2基因突变的所有表型变异，特别是在男性群体中，具体诊断可能会变得棘手，因为该基因的突变在历史上被认为仅影响女性。作者报告了一例罕见病例，该男性具有一种先前未发表的基因变异，导致了一种独特的临床表现，不符合典型或非典型雷特综合征的标准。
查阅了该患者的机构电子病历并对信息进行了审查。
发现该患者的MECP2基因存在母系遗传变异，导致了一种独特的、先前未描述过的与MECP2相关的神经发育障碍形式，表现为语言退化，随后出现言语失用和运动失调。
讨论/结论：文献报道了与MECP2基因突变相关的各种表型，并阐述了先前确定的典型和非典型雷特综合征形式。通过本病例报告，作者发现了MECP2中的一种致病变异，导致了一种先前未描述过的与MECP2相关的神经发育障碍的罕见表型。这应鼓励临床医生在诊断发育差异儿童时进行更广泛的思考。这也强化了雷特综合征或MECP2突变通常可以呈现出一系列表现，修改诊断标准以反映这一点可能是有益的。
