講演情報
[P11-12]Heyn-Sproul-Jackson症候群の１例
○二川 弘司1, 福田 憲太郎1, 山中 暖日1, 黒田 真帆1, 伊藤 志帆2, 本田 雅敬3, 鈴木 寿人4, 山田 茉未子4, 武内 俊樹4, 小崎 健次郎4, 吉橋 博史1 (1.東京都立小児総合医療センター 遺伝診療部門 臨床遺伝科, 2.東京都立小児総合医療センター 看護部, 3.東京都立小児総合医療センター 臨床試験科, 4.慶應義塾大学医学部 臨床遺伝学センター)
Introduction: Gain-of-function variant of DNMT3A(2q23.3) causes Heyn-Sproul-Jackson syndrome (MIM#618724:HESJAS) which characterized with microcephalic dwarfism and developmental delay (Heyns et al, 2019). Here, we report the oldest patient of HESJAS. Patient: 24-year-old woman. The pregnant was uncomplicated. Birth weight was below -2.0SD. At 3-year of age, she was diagnosed developmental delay. Visual acuity declined rapidly since ages of 20 due to progressive cataract. Now, her height and OFC were exceeding -4.0SD. Her dysmorphic features included microcephaly, sparse scalp hair, blepharophimosis, thin upper lip vermilion. WES (IRUD) revealed de novo pathogenic variant in DNMT3A (NM_022552.4:c.916T＞C p.Trp306Arg) that was assumed to be gain of function, and a diagnosis of HESJAS was made. Discussion: Previous reports of HESJAS have been limited to infants. In previous reports, developmental delay, severe short stature and microcephaly exceeding -4.0 SD were common findings, and this patient had similar features. The characteristic feature of present patient was the rapid loss of vision acuity in adulthood. The research of Drosophila, induced expression of Dnmt3a resulted to microphthalmia or anophthalmia. Gain-of-function variant in the DNMT3A may have caused ocular symptoms associated with HESJAS. Somatic variants in the DNMT3A are known to be associated with hematopoietic disease, and preventive health care regarding tumor development was considered for this patient. Conclusion: Management of HESJAS in adulthood should anticipate progressive ocular disease.