S. Giraud et al., A LARGE MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 FAMILY WITH CLINICAL EXPRESSION SUGGESTIVE OF ANTICIPATION, The Journal of clinical endocrinology and metabolism, 82(10), 1997, pp. 3487-3492
We describe a large multigenerational multiple endocrine neoplasia Typ
e 1 (MEN1) family with clinical expression suggestive of anticipation.
In the second and third generations, two deceased obligate gene carri
ers died at the ages of 85 and 76 without the history of MEN1, whereas
two other living gene carriers above the age of 65 have had no clinic
al evidence of MEN1 to date. In the fourth generation, eight members w
ere affected, with four having severe MEN1-related and atypical malign
ancies: a case of metastatic endocrine pancreatic tumor, two cases of
metastatic thymic carcinoids, and a case of spinal ependymoma. In the
fifth generation, all five patients were below the age of 22 when the
disease was detected. MEN1 was confirmed in the family by linkage anal
ysis using MEN1-linked microsatellite markers and by identification of
a nonsense mutation in the MEN1/menin gene. Alleotyping showed loss o
f heterozygosity (LOH) involving the wild-type alleles in seven tumors
in the family including the ependymoma, which is the first MEN1-relat
ed case that shows genetic abnormality in chromosome 11q13, suggesting
that MEN1 gene might be involved in the tumorigenesis of a subset of
ependymomas. In relation to clinical anticipation, repeated expansion
studies were carried out but failed to detect any expansion. We conclu
de that this is a unique MEN1 family and that an unknown genetic mecha
nism might be contributing to the anticipation phenomenon. We demonstr
ate in this family that all gene carriers, including the very young me
mbers, will need close and careful follow-up.