Table 2.

Genotype-Biochemical Phenotype Relationship

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.

^aPlease refer to the text for additional detail.