Risk assessment of maternally inherited<i>SDHD</i>paraganglioma and phaeochromocytoma

Burnichon, Nelly; Mazzella, Jean‐Michaël; Drui, Delphine; Amar, Laurence; Bertherat, Jérôme; Coupier, Isabelle; Delemer, Brigitte; Guilhem, Isabelle; Herman, Philippe; Kerlan, V.; Tabarin, Antoine; Wion, Nelly; Lahlou‐Laforêt, Khadija; Favier, Judith; Gimenez-Roqueplo, Anne-Paule

doi:10.1136/jmedgenet-2016-104297

Cited by 42 publications

(22 citation statements)

References 10 publications

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“…Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical, and imaging surveillance (30,40). Followup should be offered to unaffected and affected mutation carriers and relatives at risk based on family history who have not yet undergone genetic testing (2).…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that genetic testing be offered from the age of 18 years to every person whose parent has a germline SDHD mutation, and further suggested that a primary medical evaluation, including imaging, be provided for confirmed SDHD carriers (40). This recommendation includes individuals for whom the affected parent is their mother, despite the aforementioned paternal parent-of-origin effect of SDHD mutations because, although rare, there have been cases of PGL/PCC in individuals carrying a germline SDHD mutation on the maternal allele (40).…”

Section: Discussionmentioning

confidence: 99%

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Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

Gaviria¹,

Soares²,

Costa³

et al. 2019

Archives of Endocrinology and Metabolism

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Objective: Paraganglioma (PGL) and pheochromocytoma (PCC) are rare neuroendocrine tumors that were considered to be predominantly sporadic. However, with the identification of novel susceptibility genes over the last decade, it is currently estimated that up to 40% of cases can occur in the context of a hereditary syndrome. We aimed to characterize PGL/PCC families to exemplify the different scenarios in which hereditary syndromes can be suspected and to emphasize the importance for patients and their families of making an opportune genetic diagnosis. Materials and methods: Retrospective analysis of patients diagnosed with PGL/PCC. Germline mutations were studied using next-generation sequencing panels including SDHA, SDHB, SDHC and SDHD. Clinical data were collected from clinical records, and all patients received genetic counseling. Results: We describe 4 families with PGL/ PCC and germline mutations in SDH complex genes. 2 families have SDHB mutations and 2 SDHD mutations. The clinical presentation of the patients and their families was heterogeneous, with some being atypical according to the literature. Conclusions: PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. NGS multigene panel testing is a cost-effective approach given the overlapping phenotypes. Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. For all these reasons, it is critical that all medical staff can suspect and diagnose these inherited cancer predisposition syndromes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

Gaviria¹,

Soares²,

Costa³

et al. 2019

Archives of Endocrinology and Metabolism

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“…Lack of the paternal chromosome 11 does not lead to tumor initiation due to a maternal oncosuppressor locus in the 11p15 region (imprinted in the father) (81). Thus, the family history may show a "skip-generation" pattern of inheritance (73,82,83). Very rarely, loss of the paternal 11q (where SDHD allele is located) and a mitotic recombination of the maternal 11q (carrying an SDHD mutation) with the paternal 11p15 imprinted oncossupressor region may lead to the phenotypic expression of the disease, inherited from the mother (73,82,83).…”

Section: Multifocal Tumorsmentioning

confidence: 99%

Genetics of Pheochromocytoma and Paraganglioma

Pereira

Luiz

Ferreira

et al. 2019

Paraganglioma: A Multidisciplinary Approach

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Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that often develop on a background of predisposing genetic mutations. With the continuous expansion of genetic landscape of PPGL, new tools of genetic screening have been developed for simultaneous parallel sequencing of multiple genes, at faster rates and lower costs. Yet, next-generation sequencing techniques are not available worldwide and demand expertise to circumvent technical limitations and interpret results of uncertain significance, and thus a sequential genetic analysis driven by the clinical phenotype remains advisable for a successful diagnosis, and to save costs. In this chapter, we focus on the clinical features of patients with PPGLs as a framework for an optimized sequential genetic screening. We also describe new syndromes and genes that are expanding the genetic etiology of PPGLs.

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“…Lack of the paternal chromosome 11 does not lead to tumor initiation due to a maternal oncosuppressor locus in the 11p15 region (imprinted in the father) [ 91 ]. Thus, the family history may show a “skip-generation” pattern [ 49 , 92 , 93 ]. Very rarely, loss of the paternal 11q (where SDHD allele is located) and a mitotic recombination of the maternal 11q (carrying an SDHD mutation) with the paternal 11p15 imprinted oncosuppressor region may lead to the phenotypic expression of the disease, inherited from the mother [ 49 , 91 – 93 ].…”

Section: Genetic Basis Of Pediatric Pheo: Which Genes Should We Thmentioning

confidence: 99%

A Clinical Roadmap to Investigate the Genetic Basis of Pediatric Pheochromocytoma: Which Genes Should Physicians Think About?

Pereira

Silva

Bernardo

et al. 2018

International Journal of Endocrinology

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Pheochromocytoma is very rare at a pediatric age, and when it is present, the probability of a causative genetic mutation is high. Due to high costs of genetic surveys and an increasing number of genes associated with pheochromocytoma, a sequential genetic analysis driven by clinical and biochemical phenotypes is advised. The published literature regarding the genetic landscape of pediatric pheochromocytoma is scarce, which may hinder the establishment of genotype-phenotype correlations and the selection of appropriate genetic testing at this population. In the present review, we focus on the clinical phenotypes of pediatric patients with pheochromocytoma in an attempt to contribute to an optimized genetic testing in this clinical context. We describe epidemiological data on the prevalence of pheochromocytoma susceptibility genes, including new genes that are expanding the genetic etiology of this neuroendocrine tumor in pediatric patients. The clinical phenotypes associated with a higher pretest probability for hereditary pheochromocytoma are presented, focusing on differences between pediatric and adult patients. We also describe new syndromes, as well as rates of malignancy and multifocal disease associated with these syndromes and pheochromocytoma susceptibility genes published more recently. Finally, we discuss new tools for genetic screening of patients with pheochromocytoma, with an emphasis on its applicability in a pediatric population.

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Risk assessment of maternally inheritedSDHDparaganglioma and phaeochromocytoma

Cited by 42 publications

References 10 publications

Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

Genetics of Pheochromocytoma and Paraganglioma

A Clinical Roadmap to Investigate the Genetic Basis of Pediatric Pheochromocytoma: Which Genes Should Physicians Think About?

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