Multiple endocrine neoplasia 1 (MEN-1) is an inherited autosomal dominant tumour syndrome affecting mainly the parathyroid gland, pituitary and pancreas. Genetic defect appears to be deletion mutation of MEN1 gene coding for tumour suppression. We describe a case of MEN1 mosaic mutation never reported in the literature.
The index case presented aged 52 in 1985 with headaches and dizziness when hypercalcemia of 3.2 mmol/l was noted. Past medical history included stable ulcerative colitis, duodenal ulcers, renal stones and arthritis. In 1990 she had excision of an enlarged parathyroid gland and histology confirmed benign adenoma. She required further neck exploration surgeries in 1992 and 2002 for persistent hypercalcaemia and recurrence of adenoma.
When her daughter developed hypercalcaemia due to a parathyroid adenoma, we investigated the family for familial hyperparathyroidism. Mutation testing of the index case identified low level mosaicism for 188delG mutation of MEN1. This is likely to have arisen due to a sporadic mutation in a single cell of a 48 cell embryo, resulting in only a proportion of cells with the mutation. Genetic testing on her daughter confirmed heterozygous for 188delG mutation confirming germline mosaicism in index case.
Surveillance imaging of the index case in 2008 revealed a pituitary microadenoma and two pancreatic lesions (2.5×2 cm, 1.1×0.7 cm) with normal serial fasting gut peptides and pituitary function. Serial followup imaging showed stable appearances. Calcium levels remain normal.
The family described is unique for MEN1 showing a founder effect in the index case due to mutation of single cells very early in development. Mosaicism is a recognised mechanism in a number of other inherited cancer syndromes but not reported in MEN-1 to date. We could argue that a lower dose of mutated protein could explain the relatively milder clinical presentation which nevertheless leads to a classical pattern of tumour formation.