Pathogenic variants in RANBP2 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 RANBP2 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.

RANBP2的致病变异导致常染色体显性家族性和复发性儿童急性坏死性脑病（ANEC）。患病儿童通常会经历3期疾病：3到5天的非特异性发热性疾病，急性脑病以及有无神经后遗症或死亡的康复。双侧对称丘脑病变的神经放射学发现增加了对该诊断的怀疑。毁灭性疾病报道死亡率接近受影响患者的1/3，只有大约10％的患者完全康复，没有后遗症。我们报道了一个马来西亚家庭的RANBP2致病性变体c.1754C> T（p.Thr585Met）。描述了最长7年的临床表现和病程，以及3名受影响儿童的神经放射学特征。与报道的高死亡率和高发病率相比，我们的患者已康复，伴有轻微后​​遗症。我们想强调父母双方血液中都没有致病变异，这增加了父母一方种系镶嵌的可能性，作为遗传的潜在遗传机制。据我们所知，这是关于RANBP2对感染性脑病易感性的种系镶嵌的第一个报道。