title: Carney triad can be (rarely) associated with germline succinate dehydrogenase defects.
abstract: Carney triad, the association of paragangliomas/pheochromocytomas, gastrointestinal stromal tumors and pulmonary chondromas, is a sporadic condition that is significantly more frequent in females; its genetic etiology remains unknown. Carney triad is distinct from the dyad of paragangliomas/pheochromocytomas and gastrointestinal stromal tumors, known as Carney-Stratakis syndrome, which is inherited in an autosomal- dominant manner and is almost always caused by succinate dehydrogenase subunit mutations. In the present study, we investigated the largest cohort of Carney triad patients that is available internationally: 63 unrelated patients. Six patients (9.5%) were found to have germline variants in the SDHA, SDHB or SDHC genes. All six patients, except one, had multifocal gastrointestinal stromal tumors, chondromas and/or paragangliomas. A patient with Carney triad and SDHC variant had a ganglioneuroma. One of the patients with Carney triad and SDHB mutation had a nephew with the same sequence defect, who developed a neuroblastoma. Other relatives, carriers of the identified SDHA, SDHB or SDHC mutations, have not developed any of the components of Carney triad or Carney-Stratakis syndrome. None of the other 57 Carney triad patients had any genomic defects of SDHA, SDHB or SDHC genes. We conclude that, in rare occasions, Carney triad can be allelic to Carney-Stratakis syndrome. Although for the vast majority of patients with Carney triad the causative defect(s) remain(s) unknown, testing for SDHA, SDHB or SDHC variations should be offered, as carriers may develop isolated paragangliomas/pheochromocytomas and occasionally other tumors.
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Sosipatros A
authors.initials: SA
authors.lastname: Boikos
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Xekouki
authors.affiliation: Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Fumagalli
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Faucz
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Raygada
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Szarek
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Ball
authors.affiliation: Pediatric Oncology Branch (POB), National Cancer Institute (NCI), NIH, Bethesda, MD, USA.
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Diagnostic Pathology, National Cancer Institute (NCI), NIH, Bethesda, MD, USA.
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
authors.affiliation: Pediatric Oncology Branch (POB), National Cancer Institute (NCI), NIH, Bethesda, MD, USA.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Helman
authors.affiliation: Laboratory of Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J Aidan
authors.initials: JA
authors.lastname: Carney
authors.affiliation: Section on Neuroedocrinology (SNE), Program on Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD, USA.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Section on Endocrinology and Genetics (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000293:Adolescent; D000328:Adult; D002812:Chondroma / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000235:genetics*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010236:Paraganglioma, Extra-Adrenal / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase