The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2018-01-01
Date Accepted
2018-04-17
Abstract
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.
Citation
Wellcome open research, 2018, 3 pp. 46 - ?
Source Title
Publisher
F1000 Research Ltd
ISSN
2398-502X
eISSN
2398-502X
Research Team
Medicine Drug Development Unit (de Bono)
Genetic Susceptibility
Genetic Susceptibility