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Disruption of the GHRH receptor and its impact on children and adults: The Itabaianinha syndrome

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Abstract

Since 1994, we have been studying an extended kindred with 105 subjects (over 8 generations) residing in Itabaianinha County, in the Brazilian state of Sergipe, who have severe isolated GH deficiency (IGHD) due to a homozygous inactivating mutation (c.57 + 1G > A) in the GH releasing hormone (GHRH) receptor (GHRHR) gene. Most of these individuals have never received GH replacement therapy. They have low GH, and very low and often undetectable levels of serum IGF-I. Their principal physical findings are proportionate short stature, doll facies, high-pitched-voice, central obesity, wrinkled skin, and youthful hair with delayed pigmentation, and virtual absence of graying. The newborns from this cohort are of normal size, indicating that GH is not needed for intra-uterine growth. However, these IGHD individuals exhibit a myriad of phenotypic changes throughout the body, with a greater number of beneficial than harmful consequences. This GHRH signal disruption syndrome has been a valuable model to study the GH roles in body size and function. This reviews summarized the findings we have reported on this cohort.

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Acknowledgements

The authors thank the IGHD individuals for the participation in all these studies and all the many collaborators (particularly Prof. Anita H. O. Souza, who performed the fundamental population genetic study), who have contributed to these studies.

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  1. Division of Endocrinology, University Hospital, Federal University of Sergipe, Rua Claudio Batista s/n, Aracaju, Sergipe, 49060-100, Brazil

    Manuel H. Aguiar-Oliveira

  2. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine Baltimore, Baltimore, MD, 21287, USA

    Roberto Salvatori

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Correspondence to Manuel H. Aguiar-Oliveira.

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M. H. Aguiar-Oliveira has nothing to disclose. R. Salvatori serves on Novordisk advisory board.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All the participants gave informed consent.

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Aguiar-Oliveira, M.H., Salvatori, R. Disruption of the GHRH receptor and its impact on children and adults: The Itabaianinha syndrome. Rev Endocr Metab Disord 22, 81–89 (2021). https://doi.org/10.1007/s11154-020-09591-4

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