Paraganglioma after Maternal Transmission of a Succinate Dehydrogenase Gene Mutation

Pigny, Pascal; Vincent, Audrey; Bauters, C.; Bertrand, Monelle; Montpréville, Vincent Thomas de; Crépin, Michel; Porchet, Nicole; Caron, Philippe

doi:10.1210/jc.2007-1989

Cited by 80 publications

(48 citation statements)

References 19 publications

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“…22 Within this model, paraganglioma formation occurs only when the wild-type maternal SDHD allele on 11q23 and the active copy of the imprinted TSG on 11p15 are simultaneously lost. This model of inheritance has been supported by the report of Pigny et al, 24 who describe the only known case of maternal transmission of SDHDlinked paraganglioma to date. Although at first sight, this unique case seems to contradict the model, it was shown that the patient had also acquired an altered methylation profile and, therefore, probably an altered imprinted status of H19, a known paternally imprinted TSG on 11p15.…”

Section: Penetrancementioning

confidence: 59%

“…Although at first sight, this unique case seems to contradict the model, it was shown that the patient had also acquired an altered methylation profile and, therefore, probably an altered imprinted status of H19, a known paternally imprinted TSG on 11p15. 24 This suggests that the parent-of-origin-dependent inheritance of SDHD-linked disease is caused by the paternal imprinting of H19, a TSG on the imprinted 11p15 region that seems to be essential for paraganglioma formation. It furthermore suggests that maternal transmission of SDHD-linked disease is possible only if the 'second hit' targets the wild-type paternal SDHD allele on 11q23 as well as the active status of the maternal H19 allele on 11p15.…”

Section: Penetrancementioning

confidence: 99%

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The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

et al. 2009

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Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan-Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a 'wait and scan' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients.

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Section: Penetrancementioning

confidence: 59%

Section: Penetrancementioning

confidence: 99%

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

et al. 2009

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“…Multifocal tumours are more common with SDHD mutations (22). It should be noted that the tumour risk with SDHD mutations is for mutations that have been paternally inherited (maternally transmitted mutations have only very rarely been linked with disease and routine surveillance is not indicated in such cases) (24,25). Mean age at diagnosis of phaeochromocytoma in patients with SDHD mutations is 35 years (23).…”

Section: The Succinate Dehydrogenase Complexmentioning

confidence: 99%

“…SDHB mutations are an important cause of HNPGL and aPCA/eFPGL (13,23,24,26). In addition, SDHB mutations predispose to renal tumours and may present with familial renal cell carcinoma (RCC) (27).…”

Section: The Succinate Dehydrogenase Complexmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: The genetics of phaeochromocytoma: using clinical features to guide genetic testing

Jafri¹,

Maher²

2012

European Journal of Endocrinology

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Phaeochromocytoma is a rare, usually benign, tumour predominantly managed by endocrinologists. Over the last decade, major advances have been made in understanding the molecular genetic basis of adrenal and extra-adrenal phaeochromocytoma (also referred to as adrenal phaeochromocytoma (aPCA) and extra-adrenal functional paraganglioma (eFPGL)). In contrast to the previously held belief that only 10% of cases had a genetic component, currently about one-third of all aPCA/eFPGL cases are thought to be attributable to germline mutations in at least nine genes (NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, MAX and VHL). Recognition of inherited cases of aPCA/eFPGL is critical for optimal patient management. Thus, the identification of a germline mutation can predict risks of malignancy, recurrent disease, associated non-chromaffin tumours and risks to other family members. Mutation carriers should be offered specific surveillance programmes (according to the relevant gene). In this review, we will describe the genetics of aPCA/eFPGL and strategies for genetic testing. European Journal of Endocrinology 166 151-158

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“…For PGL 1, maternal imprinting of the susceptibility gene has been proposed, thus implying that only a carrier inheriting the mutation from the father will develop the disease; an exception to this rule has been observed, but the case is unclear. 22,23 The presence of several reports of familial non-syndromic cases indicates that the prevalance of inherited cases might be higher than currently recorded. 24,25 A summary of pheochromocytoma presentation in the different syndromes is represented in Table 1.…”

mentioning

confidence: 99%

Familial pheochromocytoma

Erlic¹,

Neumann²

2009

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Paraganglioma after Maternal Transmission of a Succinate Dehydrogenase Gene Mutation

Abstract: Our data show that maternal transmission of a SDHD-linked PGL, even if a rare event, can occur. Therefore, we propose that children who inherited a pathogenic mutation from their mother should be considered as at risk of PGL.

Cited by 80 publications

References 19 publications

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

GENETICS IN ENDOCRINOLOGY: The genetics of phaeochromocytoma: using clinical features to guide genetic testing

Familial pheochromocytoma

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