The phenotype of SDHB germline mutation carriers: a nationwide study

Niemeijer, Nicolasine D; Rijken, Johannes A.; Eijkelenkamp, Karin; Horst-Schrivers, Anouk N A van der; Kerstens, Michiel N.; Tops, Sophie; Berkel, Anouk van; Timmers, Henri J L M; Kunst, Henricus P. M.; Leemans, C. René; Bisschop, Peter H.; Dreijerink, Koen M.A.; Dooren, Marieke F. van; Bayley, Jean Pierre; Pereira, Alberto M.; Jansen, Jeroen C.; Hes, Frederik J.; Hensen, Erik F.; Corssmit, Eleonora P M

doi:10.1530/eje-17-0074

Cited by 39 publications

(41 citation statements)

References 22 publications

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“…However, they only had identified 1 germline SDHB mutation carrier. The genotype and phenotype of this cohort, 61 SDHB mutation carriers from the University Medical Center Groningen and 47 SDHB mutation carriers from the Leiden University Medical Center have in part been described previously . All included individuals participated in the study after written informed consent.…”

Section: Methodsmentioning

confidence: 99%

The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers

et al. 2017

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Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers).One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers. K E Y W O R D Sparaganglioma, penetrance, pheochromocytoma, SDHB

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Section: Methodsmentioning

confidence: 99%

The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers

et al. 2017

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“…In all, 54 patients, 28 female (52 per cent) and 26 male (48 per cent), with a total of 62 HNPGLs were identified in a nationwide evaluation of SDHB mutation carriers13. The mean age of diagnosis was 45·9 (range 11–77) years.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, the majority of patients with an SDHB ‐linked HNPGL reported a negative family history (70 per cent), probably reflecting the low penetrance of SDHB ‐linked PGL syndrome22 23. In addition, patients and their physicians may have been unaware that phaeochromocytomas and some non‐paraganglionic tumours such as GISTs, pituitary tumours and renal clear cell carcinomas are part of the tumour spectrum caused by SDHB germline mutations13.…”

Section: Discussionmentioning

confidence: 99%

“…The genotype and phenotype of this nationwide cohort have been described elsewhere13. SDHB mutation carriers and patients with PGL were investigated in multiple centres according to structured protocols used for standard care of PGL in the Netherlands14 15.…”

Section: Methodsmentioning

confidence: 99%

“…In a recently published nationwide evaluation of 194 SDHB mutation carriers13, 54 patients (27.8 per cent) were identified with SDHB ‐linked HNPGLs. In the present study, the clinical characteristics and clinical course, treatment modalities and outcome of these patients with HNPGL linked to SDHB mutations were evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations

et al. 2018

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BackgroundGermline mutations in the succinate dehydrogenase B (SDHB) gene predispose to hereditary paraganglioma (PGL) syndrome type 4. The aim of this study was to evaluate the clinical characteristics and outcome of treatment strategies for patients with head and neck paraganglioma (HNPGL) carrying SDHB germline mutations.MethodsThis was a retrospective evaluation of patients with HNPGL carrying SDHB germline mutations in the Netherlands.ResultsIn a Dutch nationwide cohort study of SDHB germline mutation carriers, 54 patients with a total of 62 HNPGLs were identified. Forty‐one of 54 patients (76 per cent) visited the outpatient clinic because of associated complaints. Eight patients (15 per cent) had multiple PGLs. One patient (2 per cent) developed a phaeochromocytoma and three (6 per cent) developed a malignant PGL. Twenty‐seven patients (50 per cent) had an operation for their HNPGL and 15 (28 per cent) received radiotherapy. Three patients with HNPGL (6 per cent) were diagnosed with additional non‐paraganglionic tumours.ConclusionIf an SDHB germline mutation is identified in a patient with HNPGL, the clinician should be aware of the variable manifestations of the SDHB‐linked tumour syndrome, the risk of catecholamine excess, concurrent phaeochromocytoma, and association with non‐paraganglionic tumours.

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Malignant carotid body tumors: What we know, what we do, and what we need to achieve. A systematic review of the literature

Piazza,

Lancini,

Tomasoni

et al. 2024

Head & Neck

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Malignant carotid body tumors (MCBT) are rare and diagnosed after detection of nodal or distant metastases. This systematic review (SR) focuses on MCBT initially approached by surgery. Preferred Reporting Items for SR and Meta‐Analysis (MA) guided the articles search from 2000 to 2023 on PubMed, Scopus, and Web of Science. Among 3548 papers, 132 (337 patients) were considered for SR; of these, 20 (158 patients) for MA. Malignancy rate was 7.3%, succinate dehydrogenase (SDH) mutation 17%, age at diagnosis between 4th and 6th decades, with a higher prevalence of females. MCBTs were mostly Shamblin III, with nodal and distant metastasis in 79.7% and 44.7%, respectively. Malignancy should be suspected if CBT >4 cm, Shamblin III, painful or otherwise symptomatic, at the extremes of age, bilateral, with multifocal disease, and SDHx mutations. Levels II–III clearance should be performed to exclude nodal metastases and adjuvant treatments considered on a case‐by‐case basis.

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The phenotype of SDHB germline mutation carriers: a nationwide study

Abstract: In this nationwide study of disease-affected and unaffected mutation carriers, we observed a lower rate of metastatic disease and a relatively high number of head and neck paragangliomas compared with previously reported referral-based cohorts.

Cited by 39 publications

References 22 publications

The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers

The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers

Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations

Malignant carotid body tumors: What we know, what we do, and what we need to achieve. A systematic review of the literature

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