Pheochromocytoma (Pheochromocytoma) - Genes VHL, NF1, RET, SDHA, SDHB, SDHC, SDHD and TMEM127

Pheochromocytomas are tumors of the adrenal medulla and the adrenal gland. The adrenal medulla is the main body conversion catecholamines and other hormones such as adrenaline and noradrenaline. For this reason, pheochromocytoma produces, stores and secretes catecholamines. Excess circulating catecholamine is the cause of the vast majority of symptoms associated with pheochromocytoma. The simultaneous presence of diaphoresis, tachycardia and headaches, called pheochromocytoma classic triad, is approximately 25% of cases. In half of patients hypertension is a constant, but may be absent in half of the cases, since the increase of catecholamines occurs intermittently causing, in turn, their symptoms can also be.

Most of these tumors are sporadic, but about 25-33% of cases develop as a result of germline mutations in genes encoding subunits succinildesidrogenasa (SDHA (5p15), SDHB (1p36.1-p35), SDHC (1q23.3), SDHD (11q23) or genes whose changes are due to entities like the Von Hippel-Lindau disease (VHL, 3p25.3) Neurofibromatosis type 1 (NF1, 17q11.2) or Multiple Endocrine neoplasia type 2 (RET, 10q11.2) -see Von Hippel-Lindau syndrome ... - VHL gene, Multiple Endocrine neoplasia type 2 (MEN2) - RET gene;. Neurofibromatosis type 1 (NF1) - NF1 gene - in addition to these entities, mutations in the VHL, RET, SDHA, SDHB, and SDHD TMEM127 genes increase the risk of non - syndromic paraganglioma - see non - syndromic paraganglioma -.

The succinildeshidrogenasa is an enzyme that plays a key role in cellular respiration as a component of the tricarboxylic acid cycle and respiratory chain. Mutations in these genes are Syndromes cause paraganglioma type 1 (SDHD), mainly associated with tumors of the head and neck; Type 3 (SDHC), more minority; and type 4 (SDHB), associated most often with hormonal activity lesions and cause more capacity paragangliomas malignización - see familial paraganglioma Type 1-SDHD gene; Paraganglioma Family Type 3-SDHC gene; Paraganglioma Family SDHB Maligno-gene.

Multiple Endocrine Neoplasia Type 2 (MEN2) is caused by mutations in the RET proto - oncogene, located on the long arm of chromosome 10 (10q11.2), causing its constitutive activation. Mutations responsible for multiple endocrine neoplasia type 2 give rise to a protein overactive RET probably causes the cells to grow and divide abnormally, which can lead to tumor formation in the endocrine system and other tissues. The abnormalities associated with pheochromocytomas, present in 50% of cases of MEN2, are mainly located in exons 10,11, 13 and 16.

In 10-26% of cases of Von Hippel-Lindau disease (VHLS) are pheochromocytomas. This syndrome is caused by inactivating mutations in the VHL gene, located on the short arm of chromosome 3 (3p25.3) and whose protein involved in angiogenesis and regulation of hypoxia.

Finally, may occasionally occur in adrenal pheochromocytomas 1-6% of cases of neurofibromatosis type 1. The product of the susceptibility gene, NF1, located on the long arm of chromosome 17 (17q11.2), is a negative regulator route Ras signal transduction.

The high morbidity and mortality associated with these tumors, along with the fact that most of them could be curable by surgical intervention in benign phase is essential early detection and confirmation of the diagnosis. The genetic and molecular classification of patients with pheochromocytoma is an internationally recognized tool for the diagnosis and allows better assessment of the risk of neoplasia, clinical management and genetic counseling.

Most of these tumors are sporadic. However, in about 5% of cases it occurs in families pheochromocytoma. In these cases, pheochromocytoma has an autosomal dominant inheritance, which means that a copy of the altered gene in each cell is sufficient to increase the risk of developing tumors. However, an additional mutation that eliminates the normal copy of the gene to cause the disease is needed. This second mutation, called somatic mutation, is acquired during the life of a person and is present only in tumor cells. In these familial cases it may occur alone or associated with entities such as Multiple Endocrine Neoplasia Type 2 or Von Hippel-Lindau disease.

Tests in IVAMI: in IVAMI perform mutation detection associated with the development of pheochromocytoma, by complete PCR amplification of the exons of VHL, NF1, RET, SDHA, SDHB, SDHC, SDHD and TMEM127 genes, respectively, and subsequent sequencing. Detection of large deletions and relatively common in VHL, SDHB, SDHC and SDHD genes, insertions will be made by the technique of quantitative real - time PCR (qPCR Real Time).

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).