GENETIC / FAMILIAL PHEOCHROMOCYTOMA / PARAGANGLIOMA SYNDROME
Genetic/familial pheochromocytoma/paraganglioma syndromes are inherited syndromes predisposing to pheochromocytoma and or paragangliomas.
What are the genetic Pheochromocytoma/Parangioma syndromes?
40% of patients with pheochromocytoma/paraganglioma have the disease as part of a genetic/familial syndrome, inherited through genetic mutations. However, only 10-15% of patients are aware of a family history consistent with such a genetic mutation.
TopAt what age develop and how these syndromes present?
The tumours in these syndromes develop at least a decade earlier (e.g. 29 years is the average age for mutations of the SDHB and SDHD genes), are often multiple, bilateral, coexist with other tumours, endocrine and non-endocrine, and are often multifocal.
TopWhat is the cancer risk for people with hereditary Pheochromocytoma/Paranganglioma syndromes?
Some genetic mutations are associated with an increased risk of metastases, such as mutations in the SDHB gene, which are found in 40% of metastatic pheochromocytomas/paragangliomas.
TopWhich are the genetic syndromes of pheochromocytoma/paraganglioma?
The most common genetic syndromes of pheochromocytoma/paraganglioma are the following:
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/ / / Von Hippel Lindau (VHL) disease
> What is Von Hippel Lindau disease and how does it manifest?
VHL is a familial syndrome, predisposing to the development of multiple vascular tumours, such as:
- Retinal hemangioblastomas and hemanglioblastiomas of the central nervous system
- pheochromocytomas/paragangliomas
- kidney cysts
- kidney cancer, and
- pancreatic neuroendocrine tumours
> How common is it?
The disease is inherited in the autosomal dominant pattern and its incidence is 1 in 36000 births.
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Top> At what age patients with VHL develop pheochromocytomas/paragangliomas?
The average age of pheochromocytoma/paraganglioma presentation is 28 years, while the youngest age reported is 5 years. Pheochromocytomas are often bilateral.
Top> Is there an increased risk of malignancy?
Patients with VHL disease are at increased risk of developing kidney cancer, which occurs in about 2/3 of patients.
Top> What should carriers of the disease do?
Carriers of the mutation need regular monitoring, starting at birth, for early diagnosis and treatment of tumours.
Top/ / / Neurofibromatosis
> What is Neurofibromatosis and how common is it?
Neurofibromatosis is a genetic disorder that is also inherited in an autosomal dominant pattern and its incidence is 1 in 2600-3000 individuals.
Top> What are the symptoms and signs of the disease?
Patients, during their lifetime, experience a number of clinical manifestations, such as:
- café au lait spots
- nerve tumours (neurofibromas)
- inguinal and axillary freckling
- cognitive deficits
- bony abnormalities
- tumours of the central nervous system (gliomas)
- sarcomas
- pheochromocytomas/paragangliomas
> At what age do pheochromocytomas/paragangliomas develop?
Pheochromocytoma/paraganglioma can occur at any age from infancy to old age with an average diagnosis of 42 years.
Top> Is there an increased risk of malignancy?
Patients with neurofibromatosis have an increased risk of developing malignant nerve tumours, malignant tumors of the gastrointestinal system and rhabdomyosarcomas.
Top> What should carriers of the disease do?
In this genetic syndrome as well, regular, lifetime monitoring is vital.
Top/ / / Pheochromocytoma/Paraganglioma Syndromes Due to Tricarboxylic Acid Cycle Enzymes mutations
> What are the Pheochromocytoma/Paraganglioma Syndromes due to Tricarboxylic Acid Cycle Enzymes mutations?
Such syndromes are associated with hereditary pheochromocytoma/paraganglioma and are caused by mutations in the SDHD, SDAF2, SDHC, SDHB enzymes, which are essential for energy production in cells. They are called familial paraganglioma syndrome 1, 2, 3, 4, respectively and are inherited in an autosomal dominant pattern.
Top> How do familial paraganglioma syndromes 1, 2, 3, 4 present and at what age do they develop pheochromocytomas/paragangliomas?
The most common of these syndromes is the familial paraganglioma syndrome 1, where patients develop pheochromocytomas/paragangliomas only if they inherit the mutation from their father rather than their mother. 50% of patients will develop tumours by the age of 31. On the other hand, carriers of the mutation for the SDHB gene develop pheochromocytomas/paragangliomas whether they inherit the mutation from the father or the mother.
Top> Is there an increased risk of malignancy?
Patients with familial paraganglioma syndrome 1, 2, 3, 4 have an increased risk of malignancy. For example, patients with familial paraganglioma syndrome 1 are likely to develop renal cell carcinoma and gastrointestinal stromal tumours, while carriers of the mutation for the SDHB gene have an increased risk of malignant paraganglioma and kidney cancer.
Top> What should carriers of the disease do?
Similarly, in this genetic syndrome, regular, lifelong monitoring is vital.
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