TMEM127
The TMEM127 gene is associated with hereditary paraganglioma-pheochromocytoma syndrome. Individuals with a mutation in their TMEM127 gene have an increased risk to develop pheochromocytomas (PCCs) and/or paragangliomas (PGLs). While an individual with a TMEM127 pathogenic variant will not necessarily develop cancer in their lifetime, the risk for cancer is increased over the general population risk. Affected individuals are typically diagnosed later in life (the mean age at diagnosis is 42 years), and there may be no other significant family history. The TMEM127 gene are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation.
Management
- Physical exam and blood pressure at the time of diagnosis and then every 6-12 months
- 24-hour urinary excretion of fractionated metanephrines and catecholamines and/or plasma fractionated metanephrines at least annually to detect metastatic disease, tumor recurrence, or development of additional tumors
- Follow up with imaging by CT, MRI, 123I-MIBG (metaiodobenzylguanidine) scintigraphy, or FDG-PET if the fractionated metanephrine and/or catecholamine levels become elevated, or if the original tumor had minimal or no catecholamine/fractionated metanephrine excess
- Periodic MRI or CT inclusive of head, neck, thorax, abdomen, and pelvic areas
- In order to minimize radiation exposure, MRI may be the preferable imaging modality with CT and nuclear imaging reserved to further characterize detected tumors
- Imaging modalities should be at the discretion of the managing provider due to conflicting data regarding the utility and efficacy of the various options
- Evaluation of cases with extra-adrenal sympathetic PGL and PCC for blood pressure elevations, tachycardia, and other signs and symptoms of catecholamine hypersecretion
- Medical genetics consultation
Summary of medical management and surveillance recommendations :
| Recommendation | Screening |
| Age to begin screening | 5–10 years |
| Physical exam and blood pressure | Every 6–12 months |
| Urinary excretion of fractionated metanephrines and catecholamines in 24 hours | Annually |
| Whole body MRI | Every 2–3 years |
It is recommended that people with TMEM127 gene mutations do not live in places with high elevation.
Resources