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Background: Multiple endocrine neoplasia type 2 is an autosomal dominant disorder. MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism; MEN 2B by medullary thyroid carcinoma, pheochromocytoma and characteristic stigmata. Activating germline mutations of the RET proto oncogene are responsible for this hereditary syndrome. Codon 634 mutations are the most common mutations occurring in MEN 2A families whereas a specific mutation at codon 918 is observed in the great majority of MEN 2B families. Analysis of these codons will provide a final diagnosis in the great majority of affected families making unnecessary further studies. To specifically study the codons 634 and 918 we used a minisequencing method as an alternative method to complete sequencing., Results: Using this mutation detection method we were able to reproduce in all cases, representative of 7 families, the information previously obtained by direct sequencing of PCR products. Depending on the number of primers used in the minisequencing reaction, we were able to interrogate either only one nucleotide of the target codon or the three nucleotides simultaneously., Conclusions: This technique appears as a simple, rapid and efficient method for genetic screening of MEN 2 families. It can be utilized to seek for unknown mutations at specific codons or to screen for previously identified mutations and is therefore of interest to study index cases or individuals at risk. Results suggest that complete sequencing is unnecessary.

Pituitary gigantism is a rare condition and it often has an identifiable genetic cause. In this article we report a case of a young girl with pituitary gigantism and two genetic changes. A 15-year-old girl with primary amenorrhea was diagnosed with a growth hormone (GH) and prolactin (PRL)-producing tumor, needing surgery and medical treatment with octreotide in order to achieve disease control. The co-occurrence of an AIP mutation and a MEN1 variant of uncertain significance was demonstrated in this patient. The germline mutation involving AIP was inherited from her father who at the age of 55 was unaffected and the MEN1 variant was a de novo duplication of the region 11q13.1. The latter variant, not previously reported, is unlikely to be pathogenic. Nonetheless, screening for other components of multiple endocrine neoplasia type 1 (MEN1) was performed and proved negative. The rare co-occurrence of an AIP mutation and a MEN 1 variant of uncertain significance was demonstrated in this patient. [ABSTRACT FROM AUTHOR]

Objective: Mutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross‐sectional study. Patients: SDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands. Measurements: All participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed. Results: The mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P <.001), more frequent metastases (P =.024), were more frequently subjected to surgery (P =.011) and radiotherapy (P =.013), and had worse outcomes, such as macroscopic positive margins (P =.034). Persistent and/or unresectable disease and disease‐related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P =.014). Conclusions: In this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx‐related neoplasia. Genetic testing and subsequent follow‐up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease‐free patients. [ABSTRACT FROM AUTHOR]