The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants.
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Date
2018-01-01ICR Author
Author
Tatton-Brown, K
Zachariou, A
Loveday, C
Renwick, A
Mahamdallie, S
Aksglaede, L
Baralle, D
Barge-Schaapveld, D
Blyth, M
Bouma, M
Breckpot, J
Crabb, B
Dabir, T
Cormier-Daire, V
Fauth, C
Fisher, R
Gener, B
Goudie, D
Homfray, T
Hunter, M
Jorgensen, A
Kant, SG
Kirally-Borri, C
Koolen, D
Kumar, A
Labilloy, A
Lees, M
Marcelis, C
Mercer, C
Mignot, C
Miller, K
Neas, K
Newbury-Ecob, R
Pilz, DT
Posmyk, R
Prada, C
Ramsey, K
Randolph, LM
Selicorni, A
Shears, D
Suri, M
Temple, IK
Turnpenny, P
Val Maldergem, L
Varghese, V
Veenstra-Knol, HE
Yachelevich, N
Yates, L
Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research Study,
Deciphering Developmental Disorders (DDD) Study,
Rahman, N
Type
Journal Article
Metadata
Show full item recordAbstract
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 DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novoDNMT3A 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.
Subject
Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Research Study
Deciphering Developmental Disorders (DDD) Study
Research team
Medicine Drug Development Unit (de Bono)
Genetic Susceptibility
Language
eng
Date accepted
2018-04-17
License start date
2018-01
Citation
Wellcome open research, 2018, 3 pp. 46 - ?
Publisher
F1000 Research Ltd
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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