The common genes responsible for overgrowth syndromes play key roles in regulating transcription through histone modification and chromatin modeling. The SETD2 gene encoding a H3K36 trimethyltransferase is implicated in Sotos-like syndrome. This syndrome is characterized by postnatal overgrowth, macrocephaly, obesity, speech delay, and advanced carpal ossification. We report four new patients with constitutional SETD2 mutations and review nine earlier reported patients. Almost all patients presented with macrocephaly associated with advanced stature and obesity in half of the cases. In addition to these principal manifestations, neurodevelopmental disorders are common such as intellectual disability (83%), autism spectrum disorders (89%), and behavioral difficulties (100%) with aggressive outbursts (83%). A variety of features such as joint hypermobility (29%), hirsutism (33%), and naevi (50%) were also reported. Constitutional SETD2 mutations are intragenic loss-of-function variants with truncating (69%) and missense (31%) mutations. Functional studies are necessary to improve understanding of the pathogenicity of some missense SETD2 mutations.

中文翻译：

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SETD2 相关过度生长综合征：四名新患者的介绍和文献回顾。

导致过度生长综合征的常见基因通过组蛋白修饰和染色质建模在调节转录方面发挥着关键作用。编码 H3K36 三甲基转移酶的 SETD2 基因与 Sotos 样综合征有关。这种综合征的特征是产后过度生长、巨头畸形、肥胖、语言迟缓和晚期腕骨骨化。我们报告了 4 名具有 SETD2 体质突变的新患者，并回顾了 9 名早期报告的患者。几乎所有患者都出现巨头畸形，其中一半病例伴有高身高和肥胖。除了这些主要表现外，神经发育障碍也很常见，例如智力障碍 (83%)、自闭症谱系障碍 (89%) 和具有攻击性爆发 (83%) 的行为困难 (100%)。还报告了各种特征，例如关节过度活动 (29%)、多毛症 (33%) 和痣 (50%)。构成性 SETD2 突变是具有截短 (69%) 和错义 (31%) 突变的基因内功能丧失变异。功能研究对于提高对某些错义 SETD2 突变的致病性的理解是必要的。