We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers.
No statistical significance was found between the incidence of PCC and different genotypes of codon 634 in MEN2A patients, whereas the incidence of HPT was closely associated with C634R and C634Y.
Furthermore, it would appear that C630R mirrors C634R in penetrance (100% in this family) and in early age of onset of MTC, although paradoxically, no pheochromocytomas and hyperparathyroidism have developed.
Family 2 showed the C634R mutation only in the index case, who presented with cutaneous lichen amyloidosis in addition to MTC, pheochromocytoma and hyperparathyroidism.
These data show a low frequency of hyperparathyroidism in our cases and provide further evidence that individuals with C634R as well as with C634Y mutations of the RET proto-oncogene could be at risk for parathyroid disease.