Screening for familial paragangliomas
David Myssiorek1, Alfio Ferlito, Carl E Silver
1Department of Otolaryngology, New York University School of Medicine, New York, USA.
Abstract:
Paragangliomas of the head and neck are uncommon, slow-growing, multicentric and are usually benign. Ever since familial paragangliomas were first described a genetic explanation for their existence has been sought. An international collaboration finally elucidated the SDHB, SDHC and SDHD genes for three paraganglioma syndromes (PGL 4, 3, 1). A familial origin should be suspected if other family members have paraganglioma, paragangliomas are multiple, the patient is young or the patient has a vagal paraganglioma. Once familial disease is suspected the best initial screening method is by genetic testing of the patient in question. If genetic testing detects PGL 1, 3 or 4 mutations then the patient's siblings and children should be tested. All genotypically positive patients should be followed periodically as soon as detected. Surveillance is best performed with periodic radionuclide imaging and by directed magnetic resonance imaging. The purpose of surveillance is early detection and consequently earlier treatment. Abundant evidence exists that the risk of complications from surgical intervention increases with increasing tumor size. If tumors are detected and eradicated before they become large, then younger patients can be spared the dysphagia, dysphonia, dysarthria and stroke that have plagued patients undergoing surgery for these tumors.
Insights
Genetic testing identifies familial head and neck paraganglioma syndromes (PGL 1, 3, 4) linked to SDHB, SDHC, and SDHD genes. Early screening and surveillance of at-risk relatives are crucial for timely tumor detection and treatment.
Area of Science:
- Genetics
- Oncology
- Otolaryngology
Background:
- Head and neck paragangliomas are rare, slow-growing, and typically benign tumors.
- Familial paragangliomas have been increasingly recognized, prompting research into their genetic basis.
- Previous studies have sought genetic explanations for hereditary paraganglioma syndromes.
Purpose of the Study:
- To identify the specific genes responsible for familial paraganglioma syndromes.
- To establish guidelines for screening and surveillance of individuals at risk for hereditary paragangliomas.
- To emphasize the importance of early detection and treatment to minimize surgical complications.
Main Methods:
- An international research collaboration was established to investigate familial paragangliomas.
- Genetic analysis was performed to elucidate the genes associated with paraganglioma syndromes.
- Screening protocols involving genetic testing, radionuclide imaging, and MRI were developed.
Main Results:
- The SDHB, SDHC, and SDHD genes were identified as causative for paraganglioma syndromes PGL 4, 3, and 1, respectively.
- Familial paraganglioma should be suspected in cases of multiple tumors, young age, or vagal paraganglioma.
- Genetic testing of affected individuals is the primary screening method for familial disease.
Conclusions:
- Genetic testing is essential for diagnosing familial paraganglioma syndromes (PGL 1, 3, 4) and identifying at-risk relatives.
- Periodic surveillance using radionuclide imaging and MRI allows for early detection of tumors.
- Early tumor detection and treatment can prevent severe complications such as dysphagia, dysphonia, dysarthria, and stroke.
