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Regulation of body growth

Lui, Julian C.; Garrison, Presley; Baron, Jeffrey

doi: 10.1097/MOP.0000000000000235
ENDOCRINOLOGY AND METABOLISM: Edited by Allen W. Root

Purpose of review: Recent basic studies have yielded important new insights into the molecular mechanisms that regulate growth locally. Simultaneously, clinical studies have identified new molecular defects that cause growth failure and overgrowth, and genome-wide association studies have elucidated the genetic basis for normal human height variation.

Recent findings: The Hippo pathway has emerged as one of the major mechanisms controlling organ size. In addition, an extensive genetic program has been described that allows rapid body growth in the fetus and infant but then causes growth to slow with age in multiple tissues. In human genome-wide association studies, hundreds of loci associated with adult stature have been identified; many appear to involve genes that function locally in the growth plate. Clinical genetic studies have identified a new genetic abnormality, microduplication of Xq26.3, that is responsible for growth hormone excess, and a gene, DNMT3A, in which mutations cause an overgrowth syndrome through epigenetic mechanisms.

Summary: These recent advances in our understanding of somatic growth not only provide insight into childhood growth disorders but also have broader medical applications because disruption of these regulatory systems contributes to oncogenesis.

Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA

Correspondence to Jeffrey Baron, Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Drive, MSC-1103, Bethesda, MD 20892, USA. E-mail: jeffrey.baron@nih.gov

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