Early is Better: Report of a Cowden Syndrome

Abstract

In the clinical practice, it is not common for pediatricians to visit children with overgrowth phenotype. When it happens, it is important to focus on the age of manifestations and research the pathogenic causes using appropriate genetic test. Cowden syndrome is one of these rare causes; it is an autosomal dominant genodermatosis characterized by multiple hamartomas of ectodermal, mesodermal, and endodermal origin. It is caused by loss of function mutations in the phosphatase and tensin homolog (PTEN) gene located on chromosome 10q23.1 Loss of function of the PTEN gene contributes to overgrowth and risk for a variety of cancers including breast, thyroid, endometrium, skin, kidneys, and colon. The early diagnosis of Cowden disease allows a careful monitoring of the patients who are facing the risk of cancer transformation, which is the principal complication of the condition.

Keywords

overgrowth syndrome / PTEN gene / neuroimaging

References

[1] Garofola C, Jamal Z, Gross GP.Cowden disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Accessed March 27, 2003 at: https://www.ncbi.nlm.nih.gov/books/NBK525984/

[2] Mahdi H, Mester JL, Nizialek EA, Ngeow J, Michener C, Eng C. Germline PTEN, SDHB-D, and KLLN alterations in endometrial cancer patients with Cowden and Cowden-like syndromes: an international, multicenter, prospective study. Cancer 2015; 121(05) 688-696

[3] Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 2012; 18(02) 400-407

[4] Cavaillé M, Ponelle-Chachuat F, Uhrhammer N. et al. Early onset multiple primary tumors in atypical presentation of Cowden syndrome identified by whole-exome-sequencing. Front Genet 2018; 9: 353

[5] Rademacher S, Eickholt BJ. PTEN in autism and neurodevelopmental disorders. Cold Spring Harb Perspect Med 2019; 9(11) a036780

[6] Chen CY, Chen J, He L, Stiles BL. PTEN: tumor suppressor and metabolic regulator. Front Endocrinol (Lausanne) 2018; 9: 338

[7] Ming M, He YY. PTEN in DNA damage repair. Cancer Lett 2012; 319(02) 125-129

[8] Liang H, He S, Yang J. et al. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism. Cell Metab 2014; 19(05) 836-848

[9] Dhamija R, Weindling SM, Porter AB, Hu LS, Wood CP, Hoxworth JM. Neuroimaging abnormalities in patients with Cowden syndrome: retrospective single-center study. Neurol Clin Pract 2018; 8(03) 207-213

[10] Manor J, Lalani SR. Overgrowth syndromes-evaluation, diagnosis, and management.Front Pediatr 2020;8:624141

[11] Yachelevich N. Generalized overgrowth syndromes with prenatal onset. Curr Probl Pediatr Adolesc Health Care 2015; 45(04) 97-111

[12] Richmond EJ, Rogol AD.The child with tall stature and/or abnormally rapid growth 2018. Accessed April 2020 at: The child with tall stature and/or abnormally rapid growth 2018. Accessed April 2020 at: http://www.uptodate.com

[13] Dhamija R, Hoxworth JM. Imaging of PTEN-related abnormalities in the central nervous system. Clin Imaging 2020; 60(02) 180-185

RIGHTS & PERMISSIONS

2023 Global Medical Genetics