Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Department of Pediatrics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Am J Med Genet A. 2020 Apr;182(4):673-680. doi: 10.1002/ajmg.a.61475. Epub 2020 Jan 21.
Tatton-Brown Rahman syndrome (TBRS) is an overgrowth-intellectual disability syndrome caused by heterozygous variants in DNMT3A. Seventy-eight individuals have been reported with a consistent phenotype of somatic overgrowth, mild to moderate intellectual disability, and similar dysmorphisms. We present six individuals with TBRS, including the youngest individual thus far reported, first individual to be diagnosed with tumor testing and two individuals with variants at the Arg882 domain, bringing the total number of reported cases to 82. Patients reported herein have additional clinical features not previously reported in TBRS. One patient had congenital diaphragmatic hernia. One patient carrying the recurrent p.Arg882His DNMT3A variant, who was previously reported as having a phenotype due to a truncating variant in the CLTC gene, developed a ganglioneuroblastoma at 18 months and T-cell lymphoblastic lymphoma at 6 years of age. Four patients manifested symptoms suggestive of autonomic dysfunction, including central sleep apnea, postural orthostatic hypotension, and episodic vasomotor instability in the extremities. We discuss the molecular and clinical findings in our patients with TBRS in context of existing literature.
塔顿-布朗-拉赫曼综合征（TBRS）是一种由 DNMT3A 杂合变异引起的过度生长-智力障碍综合征。已有 78 例报道，具有一致的躯体过度生长、轻度至中度智力障碍和相似的发育异常表型。我们介绍了 6 例 TBRS 患者，包括迄今为止报告的最小年龄患者、首例进行肿瘤检测诊断的患者和 2 例 Arg882 结构域变异患者，使报告的病例总数达到 82 例。本文报道的患者具有 TBRS 中以前未报道的其他临床特征。1 例患者存在先天性膈疝。1 例携带反复出现的 p.Arg882His DNMT3A 变异的患者，之前因 CLTC 基因的截断变异而被报道为具有表型，在 18 个月时发生神经节神经母细胞瘤，在 6 岁时发生 T 细胞淋巴母细胞瘤。4 例患者表现出自主神经功能障碍的症状，包括中枢性睡眠呼吸暂停、直立性低血压和四肢间歇性血管运动不稳定。我们结合现有文献讨论了 TBRS 患者的分子和临床发现。
