Table 2.
Gene | Transmission | Biochemical profile | Most common PPGL locations | Bilateral PHEO | Malignancy | Most common clinical features/tumors |
---|---|---|---|---|---|---|
EPAS/HIF2A | Unknown | NE | Multifocal sPGLs | Possible | 29% | Somatostatinoma; polycythemia; ocular lesions |
FH | AD | NE | Adrenal PPGL sPGL | Possible | 3/8 cases reported | Cutaneous and uterine leiomyoma; type 2 papillary RCC |
MAX | AD, paternal | Intermediatea | Adrenal PPGL | 67% | 7–25% | Renal oncocytoma |
MDH2 | AD | NE | sPGL | Unknown | Unknown | Unknown |
NF1 | AD | EPI | Adrenal PPGL | 16% | ~12% | Cafè-au-lait spots; neurofibromas; axillary and inguinal skin freckling; optic gliomas; iris hamartomas; pseudoarthrosis |
RET | AD | EPI | Adrenal PPGL | 50–80% | <5% | MEN2A: MTC, primary HPT MEN2B: MTC, Marfanoid habitus, mucosal ganglioneuromas |
SDHA | AD | NE; NE + DA NS | sPGL HNPGL | Unknown | 0–14% | RCC; GIST; pituitary adenoma |
SDHAF2 | AD, paternal | Unknowna | Multifocal HNPGLs | Not reported | Not reported | Not reported |
SDHB | AD | NE; NE + DA NS | sPGL | Rare | 31–71% | RCC; GIST; pituitary adenoma; pulmonary chondroma |
SDHC | AD | NS; DA NE; NE + DA | HNPGL sPGL | Unknown | 0–28% | RCC; GIST; pituitary adenoma |
SDHD | AD, paternal | NE; NE + DA NS | sPGL HNPGL | Rare | <5% | RCC; GIST; pituitary adenoma; pulmonary chondroma |
TMEM127 | AD | EPI | Adrenal PPGL | 33% | <5% | RCC |
VHL | AD | NE | Adrenal PPGL | 50% | <5% | Hemangioblastoma; RCC; PNET; ELST |
Abbreviations: AD = autosomal dominant; DA = dopamine; ELST = endolymphatic sac tumor; EPI = epinephrine; GIST = gastrointestinal stromal tumor; HNPGL = head and neck paraganglioma; HPT = hyperparathyroidism; MTC = medullary thyroid carcinoma; NE = norepinephrine; NS = nonsecreting; PNET = pancreatic neuroendocrine tumor; PPGL = pheochromocytoma and/ or paraganglioma; RCC = renal cell carcinoma; sPGL = sympathetic paraganglioma.
Please refer to the text for additional detail.