Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.
OBJECTIVE
Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations.


METHODS
Retrospective case-series.


METHODS
Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres.


METHODS
Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management.


RESULTS
Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension.


CONCLUSIONS
SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.
Srirangalingam
Umasuthan
U
Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK. u.srirangalingam@qmul.ac.uk
Walker
Lisa
L
Khoo
Bernard
B
MacDonald
Fiona
F
Gardner
Daphne
D
Wilkin
Terence J
TJ
Skelly
Robert H
RH
George
Emad
E
Spooner
David
D
Monson
John P
JP
Grossman
Ashley B
AB
Akker
Scott A
SA
Pollard
Patrick J
PJ
Plowman
Nick
N
Avril
Norbert
N
Berney
Daniel M
DM
Burrin
Jacky M
JM
Reznek
Rodney H
RH
Kumar
V K Ajith
VK
Maher
Eamonn R
ER
Chew
Shern L
SL
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D015897:Comorbidity; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
C108095:SDHB protein, human; D013385:Succinate Dehydrogenase