Early diagnosis of multiple endocrine neoplasia type 2B: a challenge for physicians

Abstract

Background:The hereditary form of medullary thyroid carcinoma may occur isolated as a familial medullary thyroid carcinoma (FMTC) or as part of Multiple Endocrine Neoplasia 2A (MEN2A) and 2B (MEN2B). MEN2B is a rare syndrome, its phenotype may usually, but not always, be noted by the physician. In the infant none of the MEN2B characteristics are present, except by early gastrointestinal dysfunction caused by intestinal neuromas. When available, genetic analysis confi rms the diagnosis and guides pre-operative evaluation and extent of surgery. Here we report four cases of MEN2B in which the late diagnosis had a signifi cant impact in clinical evolution and, potentially, in overall survival. Case Report: We report four cases, 2 men and 2 women, with differences in their phenotypes and with a late diagnosis. The fi rst case has a history of severe gastrointestinal obstruction requiring a surgery intervention two days after his birth. The second told had nodules in the oral mucosa and constipation since childhood. The third case referred a history of constipation from birth until 5 months of life. The fourth has had a history of chronic constipation since childhood. Discussion: New concepts have emerged since the RET oncogene was identifi ed in 1993 as the responsible gene for hereditary medullary thyroid carcinoma. The majority of MEN2B individuals have M918T mutation in the exon 16 of RET, with a few cases having a mutation A883F or the association of V804M with E805K, Y806C or S904C mutations. The consensus classifi es the RET mutation in codon 918 as of highest risk and recommends total thyroidectomy and central lymph node dissection until 6 months after birth. A fast and precise diagnosis is essential to reach these goals. The identifi cation of early manifestations such as intestinal ganglioneuromatosis and oral mucosal neuromas should prompt the physician to initiate an investigation for multiple endocrine neoplasia type 2B. Conclusion: The diagnosis of MEN2B is very important to allow appropriate investigation of associated diseases and to allow counseling and appropriate screening of relatives for a RET mutation. Even patients with MEN2B, which often have typical physical features, may not be properly recognized and be followed as a sporadic case. Based on this, all suspicious cases of multiple endocrine neoplasia should undergo a molecular genetic test.

M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds

“…Clinical evaluation consisted of medical history and physical examination. We particularly looked for syndromic features and the MEN 2B phenotype, including PHEO, marfanoid habitus, mucosal neuromas and ganglioneuromatosis (Camacho et al 2008).…”

Multiple Endocrine Neoplasia Type 2B: Maxillofacial Significance in 5 Cases

“…Duquia et al 16 As the syndrome has become more commonly recognized, several groups in the past 5 years have emphasized the importance of early diagnosis, a point pertinent to the present series. 12,19,[47][48][49] The 5 patients described in this review presented with many of the general features of MEN2B, such as marfanoid habitus, bone fragility, ocular lesions, chronic constipation, peripheral muscle weakness, MTC, and, in the 4 patients tested, positivity for RET mutations. All 5 exhibited consistent marfanoid disproportions and all 5 underwent thyroidectomy.…”

Diffuse intestinal ganglioneuromatosis in a child

“…Intestinal ganglioneuromatosis is most often found in patients with MEN 2B, a rare, autosomal dominant syndrome associated with medullary thyroid carcinoma (MTC) in young children. Other manifestations include pheochromocytoma, mucosal neuromas, and a marfanoid habitus [3]. Several case reports have described the diagnosis of intestinal ganglioneuromatosis in infants associated with MEN 2B [4–7].…”