Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 1;35(6):620-630.
doi: 10.1097/MOP.0000000000001298. Epub 2023 Oct 4.

Overgrowth syndromes, diagnosis and management

Steven D Klein  1   2 , Alex Nisbet  1 , Jennifer M Kalish  1   2   3   4
Affiliations
Review

Overgrowth syndromes, diagnosis and management

Steven D Klein et al. Curr Opin Pediatr. .

Abstract

Purpose of review: This review will focus on the current knowledge of the diagnosis and management of overgrowth syndromes with specific focus on mosaic conditions and treatment strategies.

Recent findings: With the implementation of massively parallel sequencing, the genetic etiology of many classically described overgrowth syndromes have been identified. More recently, the role of mosaic genetic changes has been well described in numerous syndromes. Furthermore, the role of imprinting and methylation, especially of the 11p15 region, has been shown to be instrumental for growth. Perhaps most importantly, many overgrowth syndromes carry an increased risk of neoplasm formation especially in the first 10 years of life and possibly beyond. The systematic approach to the child with overgrowth will aide in timely diagnosis and efficiently align them with appropriate screening strategies. In some cases, precision medical interventions are available to target the perturbed growth signaling pathways.

Summary: The systematic approach to the child with overgrowth aids in the standardization of the diagnostic pathway for these young patients, thereby expediting the diagnostic timeline, enabling rigorous monitoring, and delivering tailored therapeutic interventions.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

None

Figures

Figure 1:
Figure 1:
Differential diagnosis for symmetric/ubiquitous and asymmetric/mosaic overgrowth conditions. Created with BioRender.com.
Figure 2:
Figure 2:
Diagnostic algorithm and approach to the child with overgrowth, Created with BioRender.com.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Coupling deep phenotypic quantification with next-generation phenotyping for 192 individuals with germline histonopathies.
    Lubin EE, Gonzalez EM, Sangree AK, Durham EL, Klinkhammer H, Li JM, Smith SM, Layo-Carris DE, Clark KJ, Melendez-Perez AJ, Wang XM, Angireddy R, Weiss EE, Barakat TS, Mercier S, Cogné B, Koene S, Hilhorst-Hofstee Y, Rydzanicz M, Ploski R, de Los Ángeles Gómez Cano M, Palomares-Bralo M, Arévalo TB, Tan TY, Gallacher L, MacFarland SP, Ahrens-Nicklas RC, Nomakuchi TT, Bhoj EJK. Lubin EE, et al. HGG Adv. 2025 Jul 10;6(3):100440. doi: 10.1016/j.xhgg.2025.100440. Epub 2025 Apr 15. HGG Adv. 2025. PMID: 40241305 Free PMC article.

References

    1. Becker J, Gross UC, Weber DM, et al. PIK3CA Mutational Analysis in Patients With Macrodactyly. Pediatr Dev Pathol. 2022;25(6):624–34.

      Clinical case series discussing 14 PROS patients with macrodactyly found that formalin-fixed paraffin-embedded material was suitable for analysis.

    1. Shen XF, Gasteratos K, Spyropoulou GA, et al. Congenital difference of the hand and foot: Pediatric macrodactyly. J Plast Reconstr Aesthet Surg. 2022;75(11):4054–62.

      Macrodactyly in PIK3CA can be effectively treated with surgery.

    1. Zamary AR, Mamlouk MD. Neuroimaging features of genetic syndromes associated with CNS overgrowth. Pediatr Radiol. 2022;52(13):2452–66.

      **Overgrowth syndromes, in particular those related to the PI3K-AKT-mTOR pathway can result in a variety of central nervous system overgrowth signs, reviewed in this paper.

    1. Hayoun-Vigouroux M, Audebert S, Vabres P, et al. Muscle hemihypertrophy syndrome with PIK3CA gene mutation associated with Tourette syndrome. JAAD Case Rep. 2022;30:128–30.

      The authors report on a novel case of a young female patient with PROS and Tourette Syndrome.

    1. Qaisar F, Butt NI, Ajmal Ghoauri MS, et al. Proteus Syndrome: A Rare Disease Of Disproportionate And Asymmetric Overgrowth Of Connective Tissue. J Ayub Med Coll Abbottabad. 2023;35(1):177–9.

      The authors report on a novel case of Proteus syndrome diagnosed in an adult female with asymmetric overgrowth of the upper limb.

Publication types