Chew H B, Ngu L H
Department of Genetics, Kuala Lumpur Hospital, Jalan Pahang, 50586 Kuala Lumpur, Malaysia.
Mol Genet Metab Rep. 2020 Jul 27;24:100627. doi: 10.1016/j.ymgmr.2020.100627. eCollection 2020 Sep.
Pathogenic variants in cause autosomal dominant familial and recurrent Acute Necrotizing Encephalopathy of Childhood (ANEC). Affected children typically experience a 3-stage disease: a 3 to 5 days prodrome of non-specific febrile illness, acute encephalopathy, and recovery with or without neurological sequelae or death. Neuroradiological finding of bilateral symmetrical thalamic lesions raise the suspicion of this diagnosis. A devastating disease, reported mortality approaches 1/3 of those affected and only approximately 10% of patients recover completely without sequelae. We report a Malaysian family with pathogenic variant c.1754C>T (p.Thr585Met). The clinical presentation and course over a maximum of 7 years, as well as neuroradiological features of the 3 affected children are described. In contrast to the reported high mortality and morbidity, our patients have recovered with minor sequelae. We would like to highlight the absence of pathogenic variants in both parents' blood, raising the possibility of germline mosaicism in one of the parents as the underlying genetic mechanism of inheritance. To our knowledge, this is the first report of germline mosaicism in RANBP2 Susceptibility to Infection-induced Encephalopathy.
[基因名称]中的致病变异会导致常染色体显性遗传性儿童复发性急性坏死性脑病（ANEC）。患病儿童通常经历三个阶段的疾病过程：为期3至5天的非特异性发热性疾病前驱期、急性脑病，以及伴有或不伴有神经后遗症或死亡的恢复期。双侧对称性丘脑病变的神经放射学表现会引发对此诊断的怀疑。这是一种毁灭性疾病，报告的死亡率接近三分之一，只有约10%的患者能完全康复且无后遗症。我们报告了一个马来西亚家庭，其中存在致病变异c.1754C>T（p.Thr585Met）。描述了3名患病儿童长达7年的临床表现和病程，以及神经放射学特征。与报告的高死亡率和高发病率不同，我们的患者康复后仅有轻微后遗症。我们想强调的是，父母双方血液中均不存在致病变异，这增加了父母一方存在生殖系嵌合体作为潜在遗传遗传机制的可能性。据我们所知，这是RANBP2感染性脑病易感性中生殖系嵌合体的首例报告。
