Table 1.
PCC/PGL locations in hereditary syndromes
| Gene | Syndrome name | H&N | Thorax | Adrenal (PCC) | Abdominal extraadrenal | Malignancy risk |
|---|---|---|---|---|---|---|
| SDHA | − | ++ | +/− | ++ | +/− | |
| SDHB | PGL4a | + | + | + | ++ | ++ |
| SDHC | PGL3a | ++++ | +/− | +/− | +/− | +/− |
| SDHD | PGL1ab | ++ | + | ++ | ++ | +/− |
| SDHAF2 (SDH5) | PGL2 | ++++ | − | − | − | − |
| RET | MEN2c | +/− | − | ++++ | +/− | +/− |
| VHL | VHLd | +/− | +/− | ++++ | + | +/− |
| NF1 | NF1e | − | − | ++++ | +/− | + |
| TMEM127 | − | + | − | ++++ | + | − |
| MAX | − | − | − | ++++ | + | + |
− never reported, +/− <10 %, + 10–<30 %, ++ 30–<60 %, +++ 60–<90 %, ++++90–100 %
Non-KIT/PDGFRA gastrointestinal stromal tumours may be caused by mutations in the SDHB, SDHC and SDHD genes and be associated with PGL in the Carney-Stratakis syndrome.
SDHD mutation is characterized by maternal imprinting; the disease occurs only when the mutations are inherited from the father. A case of GH-secreting pituitary adenoma has been reported in a kindred with PGL1 syndrome.
Medullary thyroid carcinomas most often reveal the disease.
Von Hippel-Lindau disease is an autosomal dominant disorder, which also predisposes to renal tumours and clear cell carcinoma, pancreatic serous cystadenomas, pancreatic neuroendocrine tumours, and haemangioblastoma of the eye and central nervous system.
NF1 is characterized by the presence of multiple neurofibromas, café-au-lait spots, Lisch nodules of the iris and other rare disorders.