A complex MEN2 syndrome, a mixture of 2B and 2A, associated with a new RET germiline deletion.

Introduction: MEN2 syndromes have well-recognized phenotypes. Case report: We present the case of a 7-year-old girl with a peculiar MEN2 syndrome. The patient was born after a caesarean section at 38 weeks, with a weight of 2400 g. She had newborn jaundice, biliary vomit and failure to pass meconium. At 2-years she was submitted to an exploratory laparotomy for a big pelvic lesion and then multiple biopsy were performed. The histology described a ganglioneuroma. At 7-years she arrived at our observation with an evident marfanoid habitus, mucosal neuromas, high levels of calcitonin and thyroid nodules, central compartment and left latero-cervical lymph node lesions and a suspicious left hyperplastic parathyroid. The CT-scan showed a megacolon and described the presence of the big pelvic ganglioneuroma. A RET germline deletion in exon 11(c.1892_1899delCGAGCT; p.Glu632_ Leu633del) was found. The primary tumoral tissue, the lymph node metastases and the intestinal ganglia were screened and no additional mutations were found. She underwent to total thyroidectomy, central compartment and left latero-cervical dissection and bilateral neck exploration for primary hyperthyroidism. The histology confirmed bilateral medullary thyroid cancer with peri-thyroid soft-tissue invasion and vascular embolization, multiple central compartment and left latero-cervical lymph node metastases, a hyperplastic parathyroid (6 mm) and a parathyroid adenoma (8 mm). Conclusions: This is the first presentation of a complex MEN2 syndrome that seems to be a mixture of MEN2B and MEN2A. The underlying RET deletion involving the cysteine region had never been described at germinal level. Since we did not find any other RET alteration at germline and somatic level we could hypothesize that this mutation is causative of this complex MEN2. Nevertheless the hypothesis that the co-occurrence of MEN2A and other syndromes (i.e. MEN1) is under consideration and genes causative of these pathologies are under investigation.