To report an atypical presentation of a pathogenic STK11 gene variant in siblings not fulfilling the clinical diagnostic criteria for Peutz-Jeghers Syndrome (PJS).
Two siblings presented with prepubertal gynaecomastia and bilateral macro-orchidism, without mucocutaneous pigmentation or gastrointestinal symptoms. There was no family history of PJS. Sibling 1 had unilateral gynaecomastia. Sibling 2 had bilateral gynaecomastia, advanced bone age and bilateral testicular microlithiasis, not indicative of a large-cell calcifying Sertoli cell tumour. Genetics revealed a paternally inherited heterozygous pathogenic STK11 variant (910C>T) in both siblings. The diagnosis was confirmed following the identification of multiple intestinal polyps in their father.
Prepubertal gynaecomastia and prepubertal macro-orchidism (testicular enlargement without virilisation), always warrant endocrinological investigation, with PJS being an important differential diagnosis. Children may not fulfil the clinical criteria for a diagnosis of PJS at presentation. Genetic testing and gastroenterological investigation of parents may aid diagnosis.
Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this case report.
Ethical approval: Not applicable.
1. Latchford, A, Cohen, S, Auth, M, Scaillon, M, Viala, J, Daniels, R, et al.. Management of Peutz-Jeghers syndrome in children and adolescents: a position paper from the ESPGHAN polyposis working group. J Pediatr Gastroenterol Nutr 2019;68:442–52. https://doi.org/10.1097/mpg.0000000000002248.Search in Google Scholar PubMed
2. Ferraro, GA, Romano, T, De Francesco, F, Grandone, A, D’Andrea, F, del Giudice, EM, et al.. Management of prepubertal gynecomastia in two monozygotic twins with Peutz-Jeghers syndrome: from aromatase inhibitors to subcutaneous mastectomy. Aesthetic Plast Surg 2013;37:1012–22. https://doi.org/10.1007/s00266-013-0188-z.Search in Google Scholar PubMed
3. Zhang, L-J, Su, Z, Liu, X, Wang, L, Zhang, Q. Peutz-Jeghers syndrome with early onset of pre-adolescent gynecomastia: a predigree case report and clinical and molecular genetic analysis. Am J Transl Res 2017;9:2639–44.Search in Google Scholar
4. Ham, S, Meachem, SJ, Choong, CS, Charles, AK, Baynam, GS, Jones, TW, et al.. Overexpression of aromatase associated with loss of heterozygosity of the STK11 gene accounts for prepubertal gynecomastia in boys with Peutz-Jeghers syndrome. J Clin Endocrinol Metabol 2013;98:E1979–87. https://doi.org/10.1210/jc.2013-2291.Search in Google Scholar PubMed
5. Gourgari, E, Saloustros, E, Stratakis, CA. Large-cell calcifying sertoli cell tumors of the testes in pediatrics. Curr Opin Pediatr 2012;24:518–22. https://doi.org/10.1097/mop.0b013e328355a279.Search in Google Scholar PubMed PubMed Central
6. Crocker, MK, Gourgari, E, Lodish, M, Stratakis, CA. Use of aromatase inhibitors in large cell calcifying sertoli cell tumors: effects on gynecomastia, growth velocity, and bone age. J Clin Endocrinol Metab 2014;99:E2673–80. https://doi.org/10.1210/jc.2014-2530.Search in Google Scholar PubMed PubMed Central
7. Demirbilek, H, Bacak, G, Baran, RT, Avcı, Y, Baran, A, Keleş, A, et al.. Prepubertal unilateral gynecomastia: report of 2 cases. J Clin Res Pediatr Endocrinol 2014;6:250–3. https://doi.org/10.4274/jcrpe.1477.Search in Google Scholar
8. Renes, JS, Knijnenburg, J, Chitoe-Ramawadhdoebe, S, Gille, JJP, de Bruin, C, Barge-Schaapveld, DQCM. Possible hints and pitfalls in diagnosing Peutz-Jeghers syndrome. J Pediatr Endocrinol Metab 2018;31:1381–6. https://doi.org/10.1515/jpem-2018-0265.Search in Google Scholar PubMed
9. Ulbright, TM, Amin, MB, Young, RH. Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. Am J Surg Pathol 2007;31:827–35. https://doi.org/10.1097/pas.0b013e3180309e33.Search in Google Scholar PubMed
10. Boudeau, J, Kieloch, A, Alessi, DR, Stella, A, Guanti, G, Resta, N. Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers syndrome patients. Hum Mutat 2003;21:172. https://doi.org/10.1002/humu.9112.Search in Google Scholar PubMed
11. Resta, N, Stella, A, Susca, FC, Giacomo, MD, Forleo, G, Miccolis, I, et al.. Two novel mutations and a new STK11/LKB1 gene isoform in Peutz-Jeghers patients. Hum Mutat 2002;20:78–9. https://doi.org/10.1002/humu.9046.Search in Google Scholar PubMed
12. Lim, W, Hearle, N, Shah, B, Murday, V, Hodgson, S, Lucassen, A, et al.. Further observations on LKB1/STK11 status and cancer risk in Peutz–Jeghers syndrome. Br J Cancer 2003;89:308–13. https://doi.org/10.1038/sj.bjc.6601030.Search in Google Scholar PubMed PubMed Central
13. Yu-Liang, J, Zi-Ye, Z, Bai-Rong, L, Hao, W, En-Da, Y, Shou-Bin, N. STK11 gene analysis reveals a significant number of splice mutations in Chinese PJS patients. Cancer Genet 2019;230:47–57.10.1016/j.cancergen.2018.11.008Search in Google Scholar PubMed
© 2021 Walter de Gruyter GmbH, Berlin/Boston