Paraganglioma syndrome

• Pathogenic variants in the genes encoding different subunits of the SDH enzyme complex
• Linked to hereditary pheochromocytoma/paraganglioma
• SDHx genes
  • SDHA, SDHB, SDHC, and SDHD, SDHAF2
• Paraganglioma syndrome 1-5
  • PGL1
    • Paraganglioma syndrome 1 (PGL1) is associated with pathogenic variants in SDHD at gene locus 11q23
    • Most common
  • PGL2
    • Paraganglioma syndrome 2 (PGL2) is associated with pathogenic variants in the gene for SDH complex assembly factor 2 (SDHAF2), which is located at gene locus 11q12.2
    • To date, PGL2 has been diagnosed only in patients with an affected father, which may indicate maternal imprinting
  • PGL3
    • Paraganglioma syndrome 3 (PGL3) is associated with pathogenic variants in SDHC at locus 1q21
  • PGL4
    • Paraganglioma syndrome 4 (PGL4) is associated with pathogenic variants in SDHB at gene locus 1p36.1-35
    • Second most common type
  • PGL5
    • Paraganglioma syndrome 5 (PGL5) is associated with pathogenic variants in SDHA, which comprises 15 exons and encodes a 2390-bp transcript.