ESPE Abstracts (2022) 95 P1-188


1Ospedale Pediatrico Bambino Gesù, Roma, Italy; 2Biologist, Department of Medical Genetics, Ospedale Pediatrico Bambino Gesù, Roma, Italy; 3Doctor, Department of Pathological Anatomy, Ospedale Pediatrico Bambino Gesù, Roma, Italy

We report and discuss a case of a girl who at birth underwent surgery for Hirschsprung Disease (HD). To closely investigate her condition, we used a Next Generation Sequencing (NGS) panel to carry out a study of some of the genes known as being associated with congenital megacolon (PHOX-2B, RET, EDN3, GDNF, ASCL1 and BDNF). This analysis showed a maternally inherited heterozygous variant in the RET protooncogene (c.734T>A, p.Val245Glu), which is not described in the scientific literature and can be identified as a variant with uncertain significance (VoUS). At the age of 12.23 years, during a follow-up examination, the patient was subjected to a thyroid ultrasound that revealed the presence of a nodule of the left lobe (dimensions:12x4 mm). The nodule had a mixed ecostructure, with a transonic component and a more echogenic, apparently vascularized, solid part of 7x3 mm. We ran blood tests that showed normal values of TSH, FT4 and calcitonin. After six months, the nodule’s dimensions were doubled (24x11 mm), therefore we decided to perform a fine needle aspiration biopsy. This procedure suggested the presence of a benign nodule (TIR2). After 12 months, the nodule presented additional growth (31x17 mm) and modified ecostructure; thus we decided to proceed with surgery. In particular, given the rapid expansion of the nodule, in agreement with surgeon’s opinion, we chose total thyroidectomy rather than a hemithyroidectomy. The anatomopathological examination indeed reported the existence of an encapsulated papillary thyroid carcinoma (PT2 pNx pMx, stadium I, AJCC TNM Staging System 2017), although in a context of bilateral multifocal C cell hyperplasia, a well-known pre-carcinogenesis stage correlated with RET gene mutation. Moreover, given the reported association between RET gene rearrangements and papillary thyroid carcinomas, an NGS analysis for the identification of fusion genes (including RET gene) was carried out. The NGS did not evidence any abnormalities. RET gene mutations are usually associated with both susceptibility to HD and medullary thyroid carcinogenesis (C cell hyperplasia and medullary thyroid carcinoma). Hence, despite the detected variant is considered to be a VoUS, the patient’s clinical phenotype would highly suggest a pathogenetic RET gene variant. Accordingly, it would be worth conducting functional studies to demonstrate a potential genotype-phenotype association. Additional studies should also be undertaken to explore the possible existence of a connection between RET gene point mutation and papillary thyroid oncogenesis, even in the absence of the already known RET gene rearrangements.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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