Multiple endocrine neoplasia type 2A

Multiple endocrine neoplasia type 2A

. ). In Epidemiology and genetics MEN /uni00A0 2A has a prevalence of 1 in 25 /uni00A0 000 people. It is an auto - somal dominant condition caused by germline mutations in RET , which encodes a transmembrane tyrosine kinase recep - tor (TKR) that activates pathways involved in proliferation, survival, migration and angiogenesis. Gain-of-function RET mutations lead to activation of the TKR and cancer initiation through deregulated proliferation and increased cell survival. The mutation is sited in chromosome 10. There is a strong genotype–phenotype correlation, not seen in MEN /uni00A0 1. Clinical presentation The patterns of disease in MEN /uni00A0 2 are shown in Table 57.8 . Nearly all patients develop medullary thyroid carcinoma (MTC), which is the determinant of survival in this syndrome. PCCs are more likely to be bilateral, but are rarely malignant. PHPT is usually mild and asymptomatic and may not need surgery . A subtype of MEN /uni00A0 2, known as familial MTC (FMTC), is a variant of MEN /uni00A0 2 in which MTC occurs in isolation. MTC combined with PCC alone is known as Sipple’s syndrome.

TABLE 57.8 Genotype–phenotype associations for disorders arising from RET gene mutations. MTC (%) PHPT (%) PCC (%) Syndrome Frequently affected RET gene codons MEN /uni00A0 2A 609, 634, 90–100 20–30 10–70 790, 804 FMTC 533, 630, 90–100 – – 768, 844 MEN /uni00A0 2B 883, 918 100 – 10–60 FMTC, familial medullary thyroid carcinoma; MEN, multiple endocrine neoplasia; MTC, medullary thyroid carcinoma; PCC, phaeochromocytoma; PHPT, primary hyperparathyroidism.