Familial Pheochromocytoma: Genetics

• MEN 2: RET oncogene (tyrosine kinase) Chromosome 10 AD

• 2 A (Sipple Syndrome) 85% Codons 609,611, 618, 620,634

• 634: MTC 90%

• Pheochromocytoma 50%,

• HPTH 20%

• Cutaneous lichen amyloidosis

• 2 B 95% Codon 918: MTC

• Pheochromocytoma 50%

• Marfanoid habitus

• Mucosal neuromas/Intestinal ganglioneuromas

• Von Hippel-Laundau: VHL tumor suppressor regulates hypoxia-induced genes Chromosome 3 AD

• Pheochromocytoma (bilateral)/paraganglioma 10-20%

• Cerebellar hemangioblastoma/Retinal angioma

• Epidymal cystadenoma/Pancreatic/renal cysts

• Renal Cell Carcinoma

• Neurofibromatosis Type 1 (von Recklinghausen’s): Neurofibromin (NF1) GTPase-activating downregulates ras Chromosome 17 AD

• Café au lait >6 15 mm

• Nerofibroma >2

• Feckling axilla/inguinal areas

• Lisch nodules >2

• Optic glioma

• Sphenoid dysplasia/thinning long bones

• Affected relative

• Pheochromocytoma 2%

• Familial Paraganglioma: Mutations in succinate dehydrogenase SDHB, DDHC, SDHD

• SDHB increased risk maliganacy

• Carney Triad: Paraganglioma

• Gastric GIST

• Pulmonary chordoma