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Epidemiology of the disorders of the Pik3ca-related overgrowth spectrum (Pros)

European Journal of Human Genetics volume 31, pages 1333–1336 (2023)Cite this article

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Abstract

PIK3CA pathogenic variants are responsible for a group of overgrowth syndromes, collectively known as PIK3CA-Related Overgrowth Spectrum (PROS). These gain-of-function variants arise postzygotically, and, according to time of onset, kind of embryonal tissue affected and regional body extension, give rise to heterogeneous phenotypes. PROS rarity and heterogeneity hamper the correct estimation of its epidemiology. Our work represents the first attempt to define the prevalence of PROS according to the established diagnostic criteria and molecular analysis and based on solid demographic data. We assessed the prevalence in Piedmont Region (Italy), including in the study all participants diagnosed with PROS born there from 1998 to 2021. The search identified 37 cases of PROS born across the 25-year period, providing a prevalence of 1:22,313 live births. Molecular analysis was positive in 81.0% of participants. Taking into account the cases with a detected variant in PIK3CA (n = 30), prevalence of molecularly positive PROS was 1:27,519.

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Fig. 1: Incidence per live birth per year.

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Data availability

Depersonalized data that support the findings of this study are available within the paper and/or are available on request from the corresponding author AM.

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Acknowledgements

We are grateful to the patients and their families who made this research possible by consenting to the use of data collected as part of their care. We thank the Italian Association of individuals with PROS (Associazione Italiana Macrodattilia e PROS—APS) who contributed to this study.

Funding

No specific grant for this research was received from any funding agency in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Public Health and Pediatric Sciences, School of Medicine, University of Torino, Torino, Italy

    Giuseppe Reynolds, Simona Cardaropoli, Andrea Gazzin & Alessandro Mussa

  2. Department of Medical Science, University of Torino, Torino, Italy

    Diana Carli & Maria Luca

  3. Pediatric Dermatology, Regina Margherita Children’s Hospital, Città della Salute e della Scienza di Torino, Torino, Italy

    Paola Coppo & Roberta La Selva

  4. Medical Genetics Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) University of Bari “Aldo Moro”, 70124, Bari, Italy

    Marilidia Piglionica, Rosanna Bagnulo, Antonella Turchiano & Nicoletta Resta

  5. Analysis Laboratory “F. Ditonno” SRL, 70122, Bari, Italy

    Carlotta Ranieri

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  1. Giuseppe Reynolds
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Contributions

Conceptualization: AM, GR. Formal analysis and methodology: AM, GR. Investigation: AM, GR, SC, DC, ML, AG, PC, RLS, MP, RB, AT, CR. Resources: AM, SC, DC, ML, AG, PC, RLS, MP, RB, AT, CR, NR. Supervision: NR. Writing-original draft: AM, GR. Writing-review and editing: AM. All other authors approved this paper.

Corresponding author

Correspondence to Alessandro Mussa.

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Competing interests

The authors declare no competing interests.

Ethics approval

Given the retrospective nature of the study, approval by Ethic Committee was not required. Informed consent to genetic analysis on peripheral blood, tissue biopsy, or other samples was obtained by parents of participants and archived by authors according to the local ethic committee’s policy. Individual data included in this paper have been de-identified and presented in aggregate. The study was conducted in accordance with the ethical principles enshrined in the Helsinki Declaration.

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Reynolds, G., Cardaropoli, S., Carli, D. et al. Epidemiology of the disorders of the Pik3ca-related overgrowth spectrum (Pros). Eur J Hum Genet 31, 1333–1336 (2023). https://doi.org/10.1038/s41431-023-01414-9

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