Moyamoya Syndrome Secondary to Mitochondrial Disease in a Patient with Partial Trisomy 13q14 and 13q31: A Novel Case Report and Literature Review

Moyamoya syndrome (MMS) is a cerebrovascular disease characterized by stenosis of the internal carotid arteries and the formation of an abnormal vascular network at the base of the brain. MMS usually occurs secondary to various conditions, particularly Down syndrome, and sickle cell anemia, and presents with motor deficits, sensory symptoms, recurrent ischemic strokes, hemodynamic transient ischemic attacks, recurrent seizures, and hemorrhage. Trisomy 13 (Patau Syndrome) is a chromosomal abnormality that may be characterized by full or partial trisomy of chromosome 13. Phenotypic features of partial trisomy 13 include leukoencephalopathy, hippocampal hypoplasia, intellectual disability, facial anomalies, and others. Herein, we report a case of a 19-year-old female diagnosed with partial trisomy 13q, characterized by two large duplications in the 13q14 and 13q31 regions, with trisomy-induced bilateral MMS – the first known case to be discussed in literature. Particularly, a chromosomal microarray analysis (CMA) revealed a gain of 22Mb within the 13q14.11q21.31 region – a duplication that has not been described previously. Whole exome sequencing (WES) also revealed several mitochondrial diseases. The OMIM number, zygosity, mode of inheritance, and variants are listed for each in the Tables provided, as per the report. Both the CMA and WES can be found in the file provided. Our patient suffered four strokes between the ages of 5 and 7, later developing intractable seizures, hemiplegia, spasticity in all limbs, global delay, and regression. Despite bilateral encephaloduroarteriosynangiosis and being on several antiepileptic medications, the MMS continued to progress, confounded by the partial trisomy 13. Studies must elucidate the association between mitochondrial damage and MMS, as well as mechanisms of epilepsy associated with chromosomal abnormalities, particularly in the context of underlying mitochondrial diseases.烟雾病综合征（Moyamoya syndrome, MMS）是一类以颈内动脉狭窄及脑底异常血管网形成为特征的脑血管疾病。MMS常继发于多种病症，尤以唐氏综合征（Down syndrome）及镰状细胞贫血为代表，临床表现包括运动功能缺损、感觉异常、复发性缺血性脑卒中、血流动力学相关性短暂性脑缺血发作、复发性癫痫及颅内出血。 三体13综合征（Trisomy 13 (Patau Syndrome)）是一类以13号染色体完全或部分三体为特征的染色体异常疾病。部分三体13综合征的表型特征涵盖脑白质病、海马发育不全、智力障碍、面部畸形等。在此，我们报告1例19岁女性患者，确诊为13q部分三体综合征，其13q14及13q31区域存在两处大片段重复，并发三体诱导的双侧烟雾病综合征——此为目前文献报道的首例此类病例。 具体而言，染色体微阵列分析（chromosomal microarray analysis, CMA）显示13q14.11-q21.31区域存在22Mb的片段拷贝数增加，该重复变异此前未见文献报道。全外显子组测序（whole exome sequencing, WES）同时检出多种线粒体疾病。根据本报告，OMIM（在线人类孟德尔遗传数据库）编号、合子型、遗传模式及变异位点详见所附表格。 染色体微阵列分析及全外显子组测序的结果均可在提供的文件中获取。 该患者在5至7岁期间共发生4次脑卒中，后续出现难治性癫痫、偏瘫、四肢痉挛、全面发育迟缓及认知倒退。尽管接受了双侧脑-硬膜-动脉血管融通术（encephaloduroarteriosynangiosis）并服用多种抗癫痫药物，烟雾病综合征仍持续进展，且因合并13q部分三体而病情更为复杂。未来研究需阐明线粒体损伤与烟雾病综合征之间的关联，以及染色体异常相关癫痫的发病机制，尤其针对合并线粒体疾病的病例场景。