ESPE Abstracts

Background: Hereditary syndromic endocrine tumours are associated with significant morbidity in the paediatric population. Advances in molecular genetics enable early cascade genetic testing with early initiation of tumour screening. Controversy exists around the start age and burdens arising from screening-related harms.

Objective: To describe the efficiency of the screening program for paediatric patients with genetic risk for rare paediatric hereditary endocrine tumours.

Methods: The retrospective study was conducted over 10 years (2013-2023) in a single UK tertiary centre with collaborative paediatric and adult care. Both asymptomatic and disease‐affected paediatric patients with confirmed MEN1, MEN2, RET, PTEN, VHL and SDHx germline pathogenic variants (pv) who started screening before 18 years of age were included. Parents carrying the same pv comprised an adult cohort for comparison analysis. Clinical data including genetic testing and tumour surveillance outcomes were collected. Results are presented as median (ranges).

Results: The paediatric cohort included 63 patients age 16.2 (5.5-21.8) and the adult 35 patients age 43 (30-57). Cascade genetic testing diagnosed 80% (50/63) of the paediatric versus 48% (17/35) adults patients (P = 0.001). Tumour surveillance started earlier in the paediatric cohort at age 8.2 (3.3-15.6) years versus adult cases at age 40.2 (20-52) years (P <0.001). 52% (18/35) of adults enrolled surveillance after tumour diagnosis versus only 7% (4/63) of children. First paediatric manifestation occurred earlier at age 12 (6.6-16) than in the adult cohort at age 30 (18-52) (P <0.000). 36% (23/63) of paediatric patients developed syndrome related tumours, of which 69% (16/23) were detected via the tumour surveillance program. In the MEN1 pv paediatric carriers, primary hyperparathyroidism occurred in 37% (6/16) of the patients age 10.3 (6.6-16) years, pituitary adenomas developed in 31% (5/16) of the patients age 13.52 (11.9-15) years and pancreatic tumours were diagnosed at age 14.5 (10.6-16.6) years in 37% (6/16) of the patients. In the PTEN pv paediatric carriers, all thyroid abnormalities occurred by age 14, including 23% (3/13) with thyroid nodules and 15% (2/13) developed thyroid carcinoma, the youngest being 11 years old. Pheochromocytomas were diagnosed in two (2/6; 33%) VHL pv paediatric carriers and paragangliomas were detected in two (2/23; 8.6%) SDHB pv paediatric carriers.

Conclusion: Our data encourages the implementation of predictive genetic testing in early childhood for affected families with appropriate genetic counselling. Initiation of tumour screening program in the first decade of life reduces morbidity in paediatric patients with hereditary endocrine tumours.

Keywords: Paediatric endocrine tumour; Screening; Pathogenic variant