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6q25.1 ( TAB2 ) microdeletion syndrome: Congenital heart defects and cardiomyopathy
Author(s) -
Cheng Andrew,
Dinulos Mary Beth P.,
NeufeldKaiser Whitney,
Rosenfeld Jill,
Kyriss McKenna,
MadanKhetarpal Suneeta,
Risheg Hiba,
Byers Peter H.,
Liu Yajuan J.
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38254
Subject(s) - cardiology , cardiomyopathy , medicine , heart failure
Congenital heart defects (CHD) are the most frequent type of congenital anomaly and are often associated with genetic and chromosomal syndromes. Haploinsufficiency of TAB2 ( TGF‐beta activated kinase 1/MAP3K7 binding protein 2 ) has been proposed to cause valvular and cardiac outflow tract structural abnormalities. In this study, we describe 13 newly identified individuals with microdeletions of chromosome 6q25.1 that involve TAB2 . One of the patients in our study cohort has the smallest deletion yet reported, affecting only TAB2 . These were compared to 27 other patients reported in the published literature or DECIPHER to have similar microdeletions, for a total study group of 40 patients. Our study shows that individuals with TAB2 deletions are predisposed to developing a primary cardiomyopathy with reduced systolic function, even in the absence of CHD. Our study cohort also shares a number of non‐cardiac phenotypic findings: characteristic dysmorphic facial features, intrauterine growth restriction and/or postnatal proportionate short stature, hypotonia, developmental delay and/or intellectual disability, and connective tissue abnormalities. We conclude that a microdeletion of 6q25.1 that includes TAB2 causes a distinctive, multi‐systemic syndrome. The 6q25.1 microdeletion syndrome should be considered in a patient with cardiomyopathy or a CHD, especially valve and/or atrial or ventricular septal abnormalities, and with phenotypic features described in this study. We recommend that patients with a TAB2 deletion be screened longitudinally for systolic heart failure, even if an initial echocardiogram is normal.