Table 4.

Characteristics of the gene mutations in phaeochromocytoma and paraganglioma

Gene	Type of gene	Inheritance	Germline mutation	Somatic mutation	Mos.	GD	Predominant tumour location	Related syndrome; Associated tumours/features
SDHB	TSG	AD	10%	<1%	NR	Yes	TA>HN>PCC	Carney-Stratakis syndrome; PGL4; ccRCC, GIST; PA
SDHD	TSG	AD (P)	9–10%	<1%	NR	Yes	HN>TA>PCC	Carney-Stratakis syndrome; PGL1; ccRCC; GIST; PA
SDHC	TSG	AD	<1–5%	<1%	Yes	Yes	HN>TA>PCC	Carney-Stratakis syndrome; PGL3; clear cell renal carcinoma; GIST; PA
SDHA	TSG	AD	3%	<1%	NR	NR	TA>>PCC	PGL6; Leigh syndrome (homozygous germline mutations); ccRCC; GIST; PA
SDHAF2	TSG	AD (P)	<1%	NR	NR	NR	HN>>PCC	PGL2
FH	TSG	AD	1%	NR	NR	NR	PCC+TA>HN	Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)
VHL	TSG	AD	7–10%	10%	Yes	Yes	PCC (Bil PCC 50%)>>>TA, HN	von Hippel-Lindau syndrome; 10–25% of patients present PPGL
HIF2A (or EPAS1)	O	?	?	5–7%	Yes	-	TA>PCC	Familial erythrocytosis type 4; Pacak-Zhuang syndrome; polycythemia; somatostatinoma.
NF1	TSG	AD	<3–5%	14–25%	Yes	Yes	PCC 95% (Bil PCC 16%)>TA	von Recklinghausen’s disease
RET	O	AD	5–10%	10%	NR	-	PCC (Bil PCC 50–80%)>>>TA, HN	Multiple endocrine neoplasia type 2 (MEN2)
TMEM127	TSG	AD	<1%	NR	NR	NR	PCC (Bil PCC 33–39%)> TA, HN	PGL5/FPCC1; ccRCC
MAX	TSG	AD (P)	<1%	<2%	NR	Yes	PCC (Bil PCC 68%)>PGL	PGL7/FPCC2; PA, renal oncocytoma
HRAS	O	-	NR	7–10%	NR	-	PCC>PGL	Costello syndrome (in case of germline mutations)
MDH2	TSG	AD	<1%	NR	NR	NR	TA	Early-Onset Severe Encephalopathy (homozygous germline mutations)
SLC25A11	TSG	AD	<1%	NR	NR	NR	TA-PGL>>>HN PGL	NR
DLST	TSG	AD	<1%	NR	NR	NR	TA-PGL	NR

TSG, tumour suppressor gene; O, oncogene; ?, not clear; AD, autosomal dominant; AD (P), autosomal dominant with paternal inheritance (maternal imprinting);

NR, not reported; Mos., mosaic; GD, gross deletions; PGL, paraganglioma; PCC, phaeochromocytoma; A, abdominal PGL; TA, thoraco-abdominal PGL;

HN, head and neck PGL; Bil, Bilateral; GIST, gastrointestinal stromal tumour; ccRCC, clear cell renal cell carcinoma; PA, pituitary adenoma