6802 Exploring tonsil pathology in PTEN hamartoma syndrome

Objectives PTEN Hamartoma Tumour Syndrome (PHTS) is a heterogeneous autosomal dominant condition associated with pathogenic variants in the PTEN (Phosphatase and tensin homolog deleted on chromosome 10) gene.¹ ² PHTS encompasses a group of genetic disorders with varied clinical presentations, including macrocephaly, autism spectrum disorder, developmental delay, epilepsy, hypermobility, mucocutaneous lesions, Lhermitte-Duclos and increased cancer susceptibility.²–⁴ Recent case reports have illustrated the occurrence of tonsil-related issues in PHTS,⁵ ⁶ although there have been no cohort studies exploring tonsillar pathology in this distinct patient population. Our cohort study addresses this gap by reviewing the relationship between PHTS and tonsil pathology, particularly the prevalence, characteristics, and implications. Methods A cohort of 53 patients with PTEN mutations known to the Wessex Clinical Genetics Service were included in the study. Clinical information was extracted from local electronic patient records from April to June 2023. Age, gender distribution, genetic mutations, indications for tonsillectomy, type of surgical procedure, histology and post-operative complications were analysed. Results Tonsils issues were prevalent in 58% of the cohort, with 74% undergoing subsequent tonsillectomy. This accounted to 43% of the total cohort, significantly greater than the 13.6% of the general population undergoing tonsillectomy.⁷ Obstructive sleep apnoea (43%) was the most common primary indication for tonsillectomy, followed by recurrent tonsillitis (17%), and other causes (17%). There was a similar proportion of tonsil-related problems observed before (45%) and after (55%) PHTS diagnosis. The mean age of PHTS patients undergoing tonsillectomy was 7.8 years, with a broad age range (1 to 27 years). The predominant (87%) surgical intervention performed was tonsillectomy with adenoidectomy and 26% experienced issues post-operatively. Conclusion This study highlights the association of PHTS with tonsillar pathology throughout early life. Macrocephaly, developmental delay with or without autism and extreme tonsillar hypertrophy are indicators of an underlying PHTS diagnosis in children. Vigilant clinical evaluation by paediatricians and multidisciplinary collaboration, including the early recognition of tonsil-related manifestations and intervention are pivotal for managing PHTS patients and their associated health problems. References Liaw D, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997 Marsh DJ, et al. PTEN mutation spectrum and genotype-phenotype correlations in bannayan-riley-ruvalcaba syndrome suggest a single entity with cowden syndrome. Hum Mol Genet. 1999. Celebi JT, et al. Germline PTEN mutations in three families with Cowden syndrome. Exp Dermatol. 2000. Lachlan KL, et al. Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers. J Med Genet. 2007. Piccione M, et al. PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow-up protocol. Am J Med Genet A. 2013. Abdul LZ, et al. Bannayan Riley Ruvalcaba Syndrome. Annals Academy of Medicine. 2010. Šumilo D, et al. Incidence of indications for tonsillectomy and frequency of evidence-based surgery: a 12-year retrospective cohort study of primary care electronic records. Br J Gen Pract. 2019.