Four generations of SDHB-related disease: complexities in management

Abstract

SDHB mutations are linked to the familial paraganglioma syndrome type 4 (PGL4), which is associated with predominantly extra-adrenal disease and has high metastatic rates. Despite the lower penetrance rates in carriers of SDHB mutations compared to mutations in other paraganglioma susceptibility genes, the aggressive behavior of SDHB-linked disease warrants intensive surveillance to identify and resect tumors early. Patients with similar SDHB genotypes in whom the PGL syndrome manifests often exhibit very heterogeneous phenotypes. Tumors can arise in various locations, and management can be considerably different, depending on tumor site and pathology. We present a case series of five SDHB mutation carriers over four generations from the same family to illustrate the complexities in management.

SDHB-Associated Paraganglioma Syndrome in Africa—A Need for Greater Genetic Testing

“…Loss of SDHB staining was present in 19 specimens (36%), suggesting the presence of SDHB -associated PPGL in these cases [ 12 ]. The prevalence noted in this study is similar to that reported globally and serves to illustrate that many cases of heritable PPGL likely remain undetected in sub-Saharan Africa [ 13 , 14 ]. The paucity of reports from sub-Saharan Africa may be attributed to the limited health care resources and the lack of availability of genetic testing in the region [ 7-9 , 11 ].…”

Large Retroperitoneal Paraganglioma Associated with Germline Mutation of the Succinate Dehydrogenase Gene

“…When a PGL/PCC is suspected, the initial evaluation is completed with plasma metanephrines and CT abdomen/pelvis with IV contrast. However, in our case, the PGL was found incidentally after an abdominal ultrasound was performed for elevated liver enzymes ( 11 ). The patient’s tumor was found to be intra-abdominal and extra-adrenal which is characteristic of the more aggressive forms of sympatho-adrenal neuroendocrine tumors.…”

“…The management of patients found to have SDHB gene mutations must be tailored to the individual since presentation can be varied: age of presentation, location of the primary tumor, metastases at diagnosis, benign PGLs, and identification of concomitant non-PGL tumors. Under the direction of a multi-disciplinary team, both medical and surgical options should be utilized ( 11 ). After resection, close surveillance is particularly warranted in patients with PGL4.…”

“…After resection, close surveillance is particularly warranted in patients with PGL4. When compared to other PGL syndromes, PGL4 has a higher rate of metastasis at diagnosis, risk of recurrence, and risk of developing other primary tumors due to SDHB’s role as a tumor suppressor ( 11 , 12 ). Associations have been found between PGL4 and the development of renal cell carcinoma (14%), gastrointestinal tumors (GIST) (2%), and head and neck PGLs (20–30%) ( 5 ).…”