Figure 2.

The relationship among familial forms of hyperparathyroidism that may present as familial isolated hyperparathyroidism (FIHP) as a Venn diagram. The large dashed circle represents the set of patients that can present with a provisional diagnosis of FIHP at the time of initial ascertainment. This includes patients with FIHP who have been evaluated for, but lack findings diagnostic of, MEN1, FHH, and HPT-JT (nonsyndromic FIHP; in a solid circle). Approximately 18% of nonsyndromic FIHP kindreds harbor germline gain-of-function mutations in GCM2 (inner dotted circle) (see text), whereas the remainder have currently unknown genetic etiologies. Subsets of patients with incomplete expression of MEN1, FHH and HPT-JT (the total set of patients in each syndrome represented by a solid circle) can also present with the FIHP phenotype (and thus overlap with the large dashed circle). The distinction between the nonsyndromic FIHP category and the syndromic categories arbitrarily depends on the depth and rigor of evaluation and the sensitivity of diagnostic tests used to detect the syndrome, testing that can include germline gene mutational analysis. MEN2A is a familial form of hyperparathyroidism that seldom if ever presents as FIHP, with patients usually coming to medical attention for signs and symptoms of medullary thyroid cancer and/or pheochromocytoma. Within each circle representing a defined syndrome are included the genetic locus (or loci in the case of FHH; see text) of the syndromic trait and the associated gene product. The causative gene for HPT-JT that encodes parafibromin is CDC73, formerly called HRPT2. The relationship among the patient sets illustrated as circles in this diagram is intended to be qualitative and neither the area of each circle nor the area of overlap between circles has any quantitative significance.