Genetics of hereditary head and neck paragangliomas

Boedeker, Carsten C.; Hensen, Erik F.; Neumann, Hartmut P. H.; Maier, Wolfgang; Nederveen, Francien H. van; Suárez, Carlos; Kunst, Henricus P. M.; Rodrigo, Juan P.; Takes, Robert P.; Pellitteri, Phillip K.; Rinaldo, Alessandra; Ferlito, Alfio

doi:10.1002/hed.23436

Cited by 72 publications

(90 citation statements)

References 99 publications

(257 reference statements)

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“…During the past decade, germline mutations in more than 19 hereditary susceptibility genes resulting in PGL development have been identified [1]. More than 10 genes are associated with head and neck paragangliomas [2]. PGL now has the highest hereditary predisposition of any tumor (~40% of cases), surpassing medullary thyroid carcinoma [3].…”

Section: Introductionmentioning

confidence: 99%

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Williams

Tischler

2017

Head and Neck Pathol

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Section: Introductionmentioning

confidence: 99%

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Williams

Tischler

2017

Head and Neck Pathol

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“…However, tumours will not develop if maternal in origin, where the allele is silenced in the epigenetic "parent-of-origin" type phenomenon (so-called maternal imprinting). Therefore, tumours will only develop in SDHD mutations inherited from the father [11,31], the rare SDHAF2 mutations also exhibit this pattern [29]. SDHB mutations by contrast have lower tumour penetrance, with approximately 45% developing tumours by age 50 and without genomic imprinting [32].…”

Section: Discussionmentioning

confidence: 99%

“…Paraganglioma syndrome 1 (PGL-1) is caused by mutations of the SDHD gene (located at 11q23) and is the most common syndrome [31]. PGL1 is characterised by a predilection for head and neck lesions, which are often multifocal/bilateral [14,32].…”

Section: Pgl-1mentioning

confidence: 99%

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Head and Neck Paraganglioma: Medical Assessment, Management, and Literature Update

Hayward¹,

Cousins

2017

JOHBM

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Head and neck paraganglioma (HNPGL) are rare, highly vascular; typically slow growing and mostly benign neoplasms arising from paraganglia cells. HNPGL cause morbidity via mass effect on adjacent structures (particularly the cranial nerves), invasion of the skull base and, rarely, catecholamine secretion with associated systemic effects. The last decade has seen significant progress in the understanding of HNPGL genetics, with pertinent implications for diagnostic assessment and management of patients and their relatives. The implicated genes code for three of the five subunits of mitochondrial enzyme succinate dehydrogenase (SDH); recent literature reports that approximately one third of all HNPGL are associated with SDH mutations-a prevalence significantly greater than traditionally thought. There are distinct phenotypical syndromes associated with mutations in each individual SDH subunit (SDHD, SDHB, SDHC, and SDHAF2). This article focuses on the clinical features of HNPGL, the implications of HNPGL genetics, and the current evidence relating to optimal identification, investigation, and management options in HNPGL, which are supported by reference to a personal series of 60 cases. HNPGL require a systematic and thorough assessment to appropriately guide management decisions, and a suggested algorithm is presented in this article. Recent developments are particularly pertinent to surgeons of multiple disciplines, including otolaryngology, neurosurgery, vascular, and general surgery.

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“…Mutations of the SDHD gene are the most commonly found. Patients with SDHD gene mutations are at high risk for the development of HNPG (91-98 %) with multiple lesions as a key feature of this syndrome which can be found in the majority of patients (60-79 %) [22]. Multiple tumors, including VPG and JPG, should be managed conservatively with watchful waiting and radiotherapy in the case of growth of the tumors, particularly if bilateral, due to the devastating effects of bilateral vagus nerve palsies.…”

Section: Genetic Background Of Hnpgmentioning

confidence: 99%

Modern trends in the management of head and neck paragangliomas

Suárez

Fernández-Álvarez

Neumann³

et al. 2015

Eur Arch Otorhinolaryngol

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Head and neck paragangliomas (HNPG) are rare, mostly benign neoplasms that usually exhibit an indolent growth pattern although they can be associated with compression and infiltration of adjacent cranial nerves and, depending on the site of origin, also bone and intracranial structures. Less than 5 % of the tumors are considered malignant based on the presence of metastases and not local invasion. Carotid body tumors accounts for two-thirds of HNPG, whereas vagal paragangliomas are showing the highest tendency toward malignant character.Despite the usual treatment of benign tumors is surgery, the risks of the treatment-related complications and potential deterioration of quality of patient's live, however, should not be greater than the risk brought by the tumor in its natural course. Watchful waiting and radiotherapy are widely accepted in the management of vestibular schwannomas, a tumor that is usually indolent but, like HNPG, also has an unpredictable growth pattern. Review of different national tumor registry databases revealed that in the United States there has been a significant shift in management of vestibular schwannomas over a decade, with increasing tendency toward observation and radiotherapy, whereas the proportion of operated cases declined to near a half of the total [1][2][3]. Similar studies on the trends of treatment are lacking in HNPG. Systematic analysis of the literature has shown that most of the HNPG have been treated surgically, with no data on the impact of observation in the management of these tumors [4,5]. ''Wait and see'' policyLikewise, due to prevailingly indolent nature HNPG with low growth potential the decision on optimal treatment in HNPG is delicate, even more in view of the facts that tumor growth in individual paraganglioma (PG) case cannot be predicted and mortality caused directly by the tumor is a rare event that occurs in only 1-4 % of patients [4]. According to Jansen et al. [6], the median increase in size in a series of 48 HNPG was 0.83 mm/year. A volume increase of 20 % was noted in 60 % of the tumors, with a median increase in dimension in this subgroup of 1 mm/ year. In addition, tumor doubling time has been universally estimated as low, ranging between 4.2 and 13.8 years for HNPG [7,8].

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Genetics of hereditary head and neck paragangliomas

Abstract: All patients with HNPGs should be offered a molecular genetic screening. This screening may usually be restricted to mutations of the genes SDHD, SDHB, and SDHC. Certain clinical parameters can help to set up the order in which those genes should be tested.

Cited by 72 publications

References 99 publications

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas

Head and Neck Paraganglioma: Medical Assessment, Management, and Literature Update

Modern trends in the management of head and neck paragangliomas

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