Tatton-Brown Katrina, Zachariou Anna, Loveday Chey, Renwick Anthony, Mahamdallie Shazia, Aksglaede Lise, Baralle Diana, Barge-Schaapveld Daniela, Blyth Moira, Bouma Mieke, Breckpot Jeroen, Crabb Beau, Dabir Tabib, Cormier-Daire Valerie, Fauth Christine, Fisher Richard, Gener Blanca, Goudie David, Homfray Tessa, Hunter Matthew, Jorgensen Agnete, Kant Sarina G, Kirally-Borri Cathy, Koolen David, Kumar Ajith, Labilloy Anatalia, Lees Melissa, Marcelis Carlo, Mercer Catherine, Mignot Cyril, Miller Kathryn, Neas Katherine, Newbury-Ecob Ruth, Pilz Daniela T, Posmyk Renata, Prada Carlos, Ramsey Keri, Randolph Linda M, Selicorni Angelo, Shears Deborah, Suri Mohnish, Temple I Karen, Turnpenny Peter, Val Maldergem Lionel, Varghese Vinod, Veenstra-Knol Hermine E, Yachelevich Naomi, Yates Laura, Rahman Nazneen
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
South West Thames Regional Genetics Service, St George's University Hospitals NHS Foundation Trust, London, UK.
Wellcome Open Res. 2018 Apr 23;3:46. doi: 10.12688/wellcomeopenres.14430.1. eCollection 2018.
Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous variants. Here we have undertaken a detailed clinical study of 55 individuals with variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals) included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%); obesity (weight ³2SD, 67%); hypotonia (54%); behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%); kyphoscoliosis (33%) and afebrile seizures (22%). One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRS.
塔顿-布朗-拉赫曼综合征（TBRS；OMIM 615879），也被称为DNMT3A过度生长综合征，是一种过度生长智力障碍综合征，于2014年首次被描述，当时报告了13例携带组成型杂合变异的个体。在此，我们对55例携带变异的个体进行了详细的临床研究，其中包括之前报告的13例个体。超过80%的TBRS个体报告有智力障碍和过度生长，被指定为主要临床关联。其他常见临床关联（在20%-80%的个体中报告）包括面部外观逐渐变化，眉毛低而浓密、呈水平状，上颌中切牙突出；关节活动过度（74%）；肥胖（体重³2SD，67%）；肌张力减退（54%）；行为/精神问题（最常见的是自闭症谱系障碍，51%）；脊柱侧凸（33%）和无热惊厥（22%）。一名个体在青少年时期被诊断出患有急性髓系白血病。基于本研究结果，我们提出了目前对TBRS个体的管理方法。
