Isolated familial somatotropinomas: clinical and genetic considerations.

The majority of somatotropinomas (GH-secreting pituitary adenomas) are sporadic, through a few occur with a familial aggregation, either as a component of multiple endocrine neoplasia, type 1 (MEN1) or Carney complex, or when unassociated with other tumors, as isolated familial somatotropinomas (IFS). The latter is a rare disorder associated with loss of heterozygosity (LOH) on chromosome 11q13, the locus of the MEN1 gene. However, MEN1 sequence and expression are normal, suggesting the presence of another tumor suppressor gene within this locus that affects somatotrope proliferation. To further define the candidate interval, we performed haplotype and allelotype analyses in six families with IFS. The combined results have mapped the gene involved in the pathogenesis of IFS to a region of 9.7 Mb (7.6 cM) on chromosome 11q13.1-13.3. Identification of the IFS gene should provide new insight into the pathogenesis not only of this disorder but also of sporadic somatotropinomas.