Clinical and Molecular Features of Four Brazilian Families With Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant syndrome characterized by its clinical variability and complexity in diagnosis and treatment. We performed both clinical and molecular descriptions of four families with MEN-1 in follow-up at a tertiary center in Brasilia. We reviewed 135 medical records of patients with a clinical diagnosis of Neuroendocrine Tumors with at least two affected family members from the database of the Neuroendocrinology Outpatient Clinic of the University Hospital of Brasilia. A total of 11 patients with clinical diagnoses of MEN-1 from four families were selected. Variants in the MEN1 gene were identified in all families. One individual from each family underwent genetic testing using high-throughput sequencing (HTS). All patients had primary hyperparathyroidism (PHTP) and the second most common manifestation was a pituitary neuroendocrine tumor (PitNET). One individual had well-differentiated liposarcoma, which has been previously reported in a single case of MEN-1. Three variants previously described in the database and a novel variant in exon 2 have been found. The study allowed the genotypic and phenotypic characterization of families with MEN-1 in follow-up at a tertiary center in Brasilia.

多发性内分泌腺瘤1型（Multiple endocrine neoplasia type 1, MEN-1）是一种常染色体显性综合征，以临床异质性显著、诊断及治疗流程复杂为特征。本研究针对巴西利亚某三级医疗中心随访的4个MEN-1家系开展临床与分子特征描述。我们从巴西利亚大学附属医院神经内分泌门诊数据库中，调取了135份临床诊断为神经内分泌肿瘤（Neuroendocrine Tumors）且至少包含2名受累家庭成员的患者病历。最终从4个家系中筛选出11例经临床确诊为MEN-1的患者。所有家系均检出MEN1基因变异，每个家系各有1例患者接受了高通量测序（high-throughput sequencing, HTS）检测。所有患者均表现为原发性甲状旁腺功能亢进症（primary hyperparathyroidism, PHTP），第二常见的临床表现为垂体神经内分泌肿瘤（pituitary neuroendocrine tumor, PitNET）。1例患者合并高分化脂肪肉瘤，该表型此前仅在1例MEN-1病例中被报道。本研究共发现3个数据库中已记载的基因变异，以及1个位于外显子2的新发变异。本研究完成了巴西利亚某三级医疗中心随访的MEN-1家系的基因型与表型特征分析。