Multiple endocrine neoplasia syndromes

Two main types of multiple endocrine neoplasia syndrome exist
and both follow autosomal dominant inheritance with reduced
penetrance. Many affected people have involvement of more
than one gland but the type of tumour and age at which these
develop is very variable within families. The gene for MEN type I
on chromosome 11 acts as a tumour suppressor gene and
encodes a protein called menin. Mutations in the coding region
of the gene are found in 90% of individuals with a diagnosis of
MEN I based on clinical criteria. First-degree relatives in affected
families should be offered predictive genetic testing. Those
carrying the mutation require clinical, biochemical and
radiological screening to detect presymptomatic tumours. MEN
type II is due to mutations in the RET oncogene on chromosome
10 that encodes a tyrosine kinase receptor protein. Mutation
analysis again provides confirmation of the diagnosis in the
index case and presymptomatic tests for relatives. Screening tests
in gene carriers include calcium or pentagastrin provocation
tests that detect abnormal calcitonin secretion and permit
curative thyroidectomy before the tumour cells extend beyond
the thyroid capsule.