ESA-SRB-AOTA 2019

Cardiac paragangliomas in two siblings with SDHB mutations: challenges of management. (#527)

Simon Ryder 1 2 , Jade Eccles-Smith 1 , John Younger 3 , Amanda Love 1 , Emma Duncan 1 2 4
  1. Department of Endocrinology, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia
  2. The University of Queensland, Brisbane, QLD, Australia
  3. Department of Cardiology, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia
  4. Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia

Paragangliomas (PG) and phaeochromocytomas (PCC) are amongst the most heritable tumours. Germline mutations are identified in 35-40% of cases and to date, 21 PCC/PG susceptibility genes have been described.  SDHB is a known PCC/PG susceptibility gene, and codes for a succinate dehydronase subunit.  SDHB mutations have a penetrance of 25-40% however 25-30% of SDHB-associated tumours are malignant.

Cardiac paragangliomas (PGs) are rare (<0.3%) mediastinal tumours, comprising 1-3% of primary cardiac tumours and 2% of all PGs. Prior to functional imaging, most tumours were diagnosed only after the onset of symptoms or signs, and thus were often large and unresectable.  Cardiac PGs have been more commonly reported with SDHD mutations. 

We present two siblings from a large kindred with an SDHB mutation (c.286+2T>G (IVS3+2T>G)). Of 28 carriers, six have evidenced PGs to date, including four siblings and one of their offspring.  Two of these siblings developed cardiac PGs, identified through FDG-PET screening.  Gated cardiac MRI quantified both lesions (<2cm diameter) and both siblings underwent successful resection of their tumours. No variants in SDHD were identified (one affected sibling screened). The asymmetrical penetrance of the SDHB mutation in this kindred suggests the potential role of a modifier, however further work is required to explore this hypothesis. Furthermore, due to the rarity of condition, the approach to ongoing surveillance remains to be defined.

 

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