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Prevalence of copy number variants (CNVs) and rhGH treatment efficacy in an Italian cohort of children born small for gestational age (SGA) with persistent short stature associated with a complex clinical phenotype

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Abstract

Purpose

Multiple factors influence intrauterine growth and lead to low birth sizes. The impact of genetic alterations on both pre- and post-natal growth is still largely unknown. The aim of this study was to investigate the prevalence of CNVs in an Italian cohort of SGA children with persistent short stature and complex clinical phenotype. rhGH treatment efficacy was evaluated according to the different genotypes.

Subjects and methods

Twenty-four SGA children (10F/14M) with persistent short stature associated with dysmorphic features and/or developmental delay underwent CNV evaluation.

Results

CNVs were present in 14/24 (58%) SGA children. Six patients had a microdeletion involving the following regions: 3q24q25.1, 8p21.2p12, 15q26, 19q13.11, 20q11.21q12, 22q11.2. In three females, the same microdeletion involving 17p13.3 region was identified. In two different patients, two microduplications involving 10q21.3 and Xp11.3 region were observed. A further female patient showed both an 11q12.1 and an Xq27.1 microduplication, inherited from her mother and from her father, respectively. In a boy, the presence of a 12p13.33 microdeletion and a 19q13.43 microduplication was found. GH treatment efficacy, expressed by height gain and height velocity in the first 12 months of therapy, was similar in subjects with and without CNVs.

Conclusions

These results show that pathogenic CNVs are common in SGA children with short stature associated with additional clinical features. Interestingly, the involvement of 17p13.3 region occurs with a relative high frequency, suggesting that genes located in this region could play a key role in pre- and post-natal growth. rhGH therapy has similar efficacy in the short term whether CNVs are present or not.

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Funding

This work was supported by Ministero della Salute grant, 2019: RRC-2019-2366867.

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Authors and Affiliations

  1. Dipartimento Pediatrico Universitario Ospedaliero, IRCCS “Bambino Gesù” Children’s Hospital, Rome, Italy

    E. Inzaghi, A. Deodati, F. Verdecchia, M. Cappa & S. Cianfarani

  2. Translational Cytogenomics Research Unit, IRCCS “Bambino Gesù” Children’s Hospital, Rome, Italy

    S. Loddo, M. Mucciolo, E. Sallicandro, G. Catino & A. Novelli

  3. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

    S. Cianfarani

  4. Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden

    S. Cianfarani

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  1. E. Inzaghi
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Correspondence to E. Inzaghi.

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Inzaghi, E., Deodati, A., Loddo, S. et al. Prevalence of copy number variants (CNVs) and rhGH treatment efficacy in an Italian cohort of children born small for gestational age (SGA) with persistent short stature associated with a complex clinical phenotype. J Endocrinol Invest 45, 79–87 (2022). https://doi.org/10.1007/s40618-021-01617-1

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