We report three Japanese patients with Sotos syndrome accompanied by marked overgrowth, i.e., a 2 8/12-year-old boy with a height of 105.2 cm (+4.4 SD) (patient 1), the mother of patient 1 with a height of 180.8 cm (+4.1 SD) (patient 2), and a 12 10/12-year-old girl with a height of 189.4 cm (+6.3 SD) (patient 3). In addition to the marked overgrowth (tall stature), patients 1–3 exhibited Sotos syndrome-compatible macrocephaly and characteristic features, whereas intellectual and developmental disabilities remained at a borderline level in patient 1 and were apparently absent from patients 2 and 3. Thus, whole exome sequencing was performed to confirm the diagnosis, revealing a likely pathogenic c.6356A>G:p.(Asp2119Gly) variant in NSD1 of patients 1 and 2, and a likely pathogenic c.6599dupT:p.(Ser2201Valfs*4) variant in NSD1 of patient 3 (NM_022455.5). The results, in conjunction with the previously reported data in nine patients with marked overgrowth (≥4.0 SD), imply that several patients with Sotos syndrome have extreme tall stature even in adulthood. Thus, it is recommended to examine NSD1 in patients with marked overgrowth as the salient feature.

我们报告了三名患有 Sotos 综合征并伴有明显过度生长的日本患者，即一名 2 8/12 岁男孩，身高 105.2 cm (+4.4 SD)（患者 1），患者 1 的母亲身高 105.2 cm (+4.4 SD)。 180.8 厘米（+4.1 标准差）（患者 2），以及一名 12 10/12 岁女孩，身高 189.4 厘米（+6.3 标准差）（患者 3）。除了明显的过度生长（身材高大）外，患者 1-3 还表现出与索托斯综合征相容的大头畸形和特征性特征，而患者 1 的智力和发育障碍仍处于临界水平，而患者 2 和 3 显然不存在。通过全外显子组测序来确认诊断，结果显示患者 1 和 2 的NSD1中可能存在致病性 c.6356A>G:p.(Asp2119Gly) 变异，以及可能存在致病性 c.6599dupT:p.(Ser2201Valfs*4) 变异在患者 3 的NSD1中(NM_022455.5)。该结果与之前报道的九名明显过度生长（≥4.0 SD）患者的数据相结合，表明一些索托斯综合征患者即使在成年后也具有极高的身材。因此，建议检查以明显过度生长为显着特征的患者的NSD1 。