Background: Multiple endocrine neoplasia type I (MEN1) is characterized by the combined occurrence of tumours in several endocrine tissues such as parathyroid tumours, pituitary tumours (usually prolactinomas) and pancreatic neuroendocrine tumours. MEN1 is an autosomal dominant disorder caused by germline mutations in the tumour suppressor gene MEN1. First-degree relatives of a germline MEN1 mutation carrier have a 50% risk of the mutation. Intensive surveillance of germline carriers starts at age 5 years.
Case presentation: The index patient in this family presented at age 16 years with primary amenorrhoea, caused by a prolactinoma. At the age of 26 years she had urolithiasis, because of primary hyperparathyroidism. Germline DNA testing showed a heterozygous deletion of the MEN1 gene (c.-101-?_1848+?del). Surprisingly neither her father (known with urolithiasis), nor her mother appeared to carry the same germline MEN1 mutation. Because somatic mosaicism in the parents could be present, her brother was tested and was found to have the MEN1 mutation. Surveillance showed hyperparathyroidism and a thymus carcinoid. Then their father was diagnosed with a pancreatic neuro-endocrine tumour. Tumour DNA analysis showed the same MEN1 mutation as in the germline of both his children.
Conclusion: This is the first reported case of combined germline and somatic mozaicism for a MEN1 mutation. This family history shows that in families with an apparent de novo genetic mutation, germline mozaicism is important to consider. Especially in cancer syndromes, it has major implications for the familys surveillance, treatment and prognosis.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology