AUTHOR=Huttunen Heta , Hero Matti , Lääperi Mitja , Känsäkoski Johanna , Swan Heikki , Hirsch Joel A. , Miettinen Päivi J. , Raivio Taneli 

TITLE=The Role of KCNQ1 Mutations and Maternal Beta Blocker Use During Pregnancy in the Growth of Children With Long QT Syndrome

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00194

DOI=10.3389/fendo.2018.00194

ISSN=1664-2392

ABSTRACT=<sec id="ST1"><title>Objective</title><p>Two missense mutations in <italic>KCNQ1</italic>, an imprinted gene that encodes the alpha subunit of the voltage-gated potassium channel Kv7.1, cause autosomal dominant growth hormone deficiency and maternally inherited gingival fibromatosis. We evaluated endocrine features, birth size, and subsequent somatic growth of patients with long QT syndrome 1 (LQT1) due to loss-of-function mutations in <italic>KCNQ1</italic>.</p></sec><sec id="ST2"><title>Design</title><p>Medical records of 104 patients with LQT1 in a single tertiary care center between 1995 and 2015 were retrospectively reviewed.</p></sec><sec id="ST3"><title>Methods</title><p>Clinical and endocrine data of the LQT1 patients were included in the analyses.</p></sec><sec id="ST4"><title>Results</title><p>At birth, patients with a maternally inherited mutation (<italic>n</italic> = 52) were shorter than those with paternal inheritance of the mutation (<italic>n</italic> = 29) (birth length, −0.70 ± 1.1 SDS vs. −0.2 ± 1.0 SDS, <italic>P</italic> &lt; 0.05). Further analyses showed, however, that only newborns (<italic>n</italic> = 19) of mothers who had received beta blockers during pregnancy were shorter and lighter at birth than those with paternal inheritance of the mutation (<italic>n</italic> = 29) (−0.89 ± 1.0 SDS vs. −0.20 ± 1.0 SDS, <italic>P</italic> &lt; 0.05; and 3,173 ± 469 vs. 3,515 ± 466 g, <italic>P</italic> &lt; 0.05). Maternal beta blocker treatment during the pregnancy was also associated with lower cord blood TSH levels (<italic>P</italic> = 0.011) and significant catch-up growth during the first year of life (Δ0.08 SDS/month, <italic>P</italic> = 0.004). Later, childhood growth of the patients was unremarkable.</p></sec><sec id="ST5"><title>Conclusion</title><p>Loss-of-function mutations in <italic>KCNQ1</italic> are not associated with abnormalities in growth, whereas maternal beta blocker use during pregnancy seems to modify prenatal growth of LQT1 patients—a phenomenon followed by catch-up growth after birth.</p></sec>