ESPE Abstracts

Background: Multiple endocrine neoplasia type 2B is a rare genetic syndrome caused by germline mutations in the RET proto-oncogene. Approximately 75% of MEN2B cases are sporadic and caused by de novo RET mutations, whereas 25% of cases occurs in families with an autosomal dominant inheritance. The most common RET mutation found in 95% of MEN2B patients is the substitution of the amino-acid threonine for methionine at codon 918. In infants with de novo mutation of the RET codon M918T, the diagnosis of MEN2B is usually delayed than the appearance of medullary thyroid carcinoma; in fact the majority of these patients show extra endocrine features during childhood.

Case reports: We report three cases of MEN 2B syndrome referred at our Endocrinology Unit for extra endocrine features.

Patient 1: a 17 months old male referred for episodes of central apnoea associated with cyanosis since 4 months of age. He also showed prominent lips and chronic constipation. To rule out congenital hypoventilation syndromes, we excluded by array-CGH genetic conditions of hypoventilation. Then we assessed whole exome sequencing that revealed the de novo heterozygous missense variant c. 2753T>C (P.Met918Thr) in RET gene.

Patient 2: a 17 months old male child evaluated for generalized hypotonia and delayed psychomotor development with full lips, macroglossia and relative macrocrania. Moreover, he showed chronic constipation since weaning and monocular alacrimia. Based on clinical features overgrowth syndrome was excluded through genetic test that showed de novo missense heterozygous variant, c.2753T>C (P.Met918Thr), in RET gene.

Patient 3: a 6-year-old male child referred for growth retardation. During first months of life he showed keratoconjunctivitis and alacrimia associated with constipation and intellectual disability. Based on clinical features and history, we assessed calcitonin level (872 pg/ml; nr < 9.5 pg/ml), thyroid function (normal FT4 and TSH). We confirmed our hypothesis by genetic test that showed de novo missense mutation c.2753T>C (P.Met918Thr) in RET gene.

Conclusion: MEN2B is an extremely rare condition associated with variability of clinical signs and symptoms. Our cases confirm the importance related to identify extra endocrine signs in these patients. This approach can contribute to detecting early potential neoplastic endocrine lesions (medullary thyroid cancer) and improve the average survival.