Sotos syndrome with marked overgrowth in three Japanese patients with heterozygous likely pathogenic NSD1 variants: case reports with review of literature

• Published in: Endocrine Journal Vol. 71; no. 1; pp. 75 - 81
• Main Authors: Masunaga, Yohei, Ono, Hiroyuki, Fujisawa, Yasuko, Taniguchi, Kiyosu, Saitsu, Hirotomo, Ogata, Tsutomu
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 01.01.2024; Japan Science and Technology Agency
• Subjects: Adult; Case reports; Developmental disabilities; Female; Histone Methyltransferases; Histone-Lysine N-Methyltransferase - genetics; Humans; Intellectual disabilities; Intracellular Signaling Peptides and Proteins - genetics; Japan; Male; Mutation; Nuclear Proteins - genetics; Nuclear receptor binding SET domain protein 1 (NSD1); Overgrowth; Patients; Sotos syndrome; Sotos Syndrome - diagnosis; Sotos Syndrome - genetics; Whole exome sequencing; Japan; Overgrowth; Sotos syndrome; Whole exome sequencing; Nuclear receptor binding SET domain protein 1 (NSD1)
• ISSN: 0918-8959; 1348-4540; 1348-4540
• DOI: 10.1507/endocrj.EJ23-0502

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.