Genetic testing and surveillance of mutation carriers for hereditary paraganglioma syndromes has rapidly improved. Very poor prognosis is seen in approximately 25% of SDHB mutation carriers, yet low disease penetrance (25-40%) means that many SDHB mutation carriers undergoing surveillance will never develop disease. Current Australian surveillance guidelines (EviQ) suggest annual blood pressure and plasma metanephrines, and 2-yearly whole-body MRI. However, gadolinium toxicity is now recognised, and MRI scanning is time-consuming, costly and not widely available.
Cardiac paragangliomas are rare (<0.3%) mediastinal tumours, comprising 1-3% of primary cardiac tumours. Prior to functional imaging, most tumours were diagnosed only after onset of symptoms or signs, and thus were often large and unresectable.
We present a large kindred (68 people), of whom 28 (41%) carry an SDHB mutation (c.286+2T>G (IVS3+2T>G) in intron 3). Seventeen undergo annual surveillance at Royal Brisbane and Women’s Hospital (RBWH). To date, six individuals in the entire pedigree have developed paraganglioma. Apart from one individual, all other cases are from one family. This family includes a carrier father, five carrier children of whom four have developed paragangliomas including two cardiac paragangliomas. None of the other SDHB mutation carriers in the family has evidenced disease, despite screening. The familial clustering of paragangliomas generally, and cardiac paraganglioma specifically, suggest the existence of a genetic or environmental modifier in this family branch.
Both cardiac paragangliomas were diagnosed on FDG-PET where no lesion was visible on whole-body MRI. Gated cardiac MRI quantified both lesions (<2cm diameter) which were successfully resected. The literature suggests that Ga-DOTATATE has excellent sensitivity and specificity for detection of SDHx-associated tumours.
Identification of a potential modifier in this family would allow for more targeted surveillance, which as a consequence of the experience described above now incorporates second yearly imaging (alternating MRI with Ga-DOTATATE) irrespective of functional assessment.