Carney-Stratakis Syndrome Caused by a Novel SDHD Mutation (original) (raw)
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Paraganglioma syndrome type 1 in a patient with Carney–Stratakis syndrome
Nature Reviews Endocrinology, 2010
Background. A 33-year-old man was referred to a specialist center with a left neck mass and hypertension. The patient underwent surgery, which confirmed a malignant neck paraganglioma with metastasis to a cervical lymph node. He had no family history of carotid body tumors or pheochromocytoma. Investigations. Measurements of plasma free metanephrines and chromogranin A; radiographic evaluations with CT, 18 F-fluorodeoxyglucose PET and 123 I-labeled metaiodobenzylguanidine scan; gene analysis for mutations in the SDHD and the KIT gene. Diagnosis. Paraganglioma syndrome type 1 in a patient with a paraganglioma, bilateral pheochromocytomas and a gastrointestinal stromal tumor with a somatic Asp579del KIT mutation. Management. The patient underwent surgical excision of all tumors after adequate preparation with alpha and beta blockers. Blood pressure normalized after surgery. The patient is examined regularly with biochemical and radiographic studies, and his follow-up is expected to last throughout life.
Carney-Stratakis Syndrome presenting as occult mediastinal paraganglioma
Radiology Case Reports, 2020
Carney-Stratakis Syndrome is defined as the combination of a paraganglioma and a gastrointestinal stromal tumor. This is recognized as unique from the more commonly known Carney Triad, which in addition to the above also has a pulmonary chondroma present. We present a case of Carney-Stratakis Syndrome which highlights the value of multimodality imaging in arriving at the diagnosis, as well as the role of genetic testing for definitively differentiating it from the more commonly recognized Carney Triad.
European Journal of Human Genetics, 2008
Gastrointestinal stromal tumors (GISTs) may be caused by germline mutations of the KIT and plateletderived growth factor receptor-a (PDGFRA) genes and treated by Imatinib mesylate (STI571) or other protein tyrosine kinase inhibitors. However, not all GISTs harbor these genetic defects and several do not respond to STI571 suggesting that other molecular mechanisms may be implicated in GIST pathogenesis. In a subset of patients with GISTs, the lesions are associated with paragangliomas; the condition is familial and transmitted as an autosomal-dominant trait. We investigated 11 patients with the dyad of 'paraganglioma and gastric stromal sarcoma'; in eight (from seven unrelated families), the GISTs were caused by germline mutations of the genes encoding subunits B, C, or D (the SDHB, SDHC and SDHD genes, respectively). In this report, we present the molecular effects of these mutations on these genes and the clinical information on the patients. We conclude that succinate dehydrogenase deficiency may be the
Modern Pathology, 2010
Mutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. However, other tumors have been associated with SDHx mutations, such as gastrointestinal stromal tumors (GISTs) specifically in the context of Carney-Stratakis syndrome. Previously, we have shown that SDHB immunohistochemistry is a reliable technique for the identification of pheochromocytomas and paragangliomas caused by SDHx mutations. We hypothesized that GISTs in patients with SDHx mutations would be negative immunohistochemically for SDHB as well. Four GISTs from patients with Carney-Stratakis syndrome and six from patients with Carney triad were investigated by SDHB immunohistochemistry. Five GISTs with KIT or PDGFRA gene mutations were used as controls. In addition, SDHB immunohistochemistry was performed on 42 apparently sporadic GISTs. In cases in which the SDHB immunohistochemistry was negative, mutational analysis of SDHB, SDHC, and SDHD was performed. All GISTs from patients with Carney-Stratakis syndrome and Carney triad were negative for SDHB immunohistochemically. In one patient with Carney-Stratakis syndrome, a germline SDHB mutation was found (p.Ser92Thr). The five GISTs with a KIT or PDGFRA gene mutation were all immunohistochemically positive for SDHB. Of the 42 sporadic tumors, one GIST was SDHB-negative. Mutational analysis of this tumor did not reveal an SDHx mutation. All SDHB-negative GISTs were located in the stomach, had an epithelioid morphology, and had no KIT or PDGFRA mutations. We show that Carney-Stratakis syndromeand Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT-or PDGFRA-mutated GISTs and a majority of sporadic GISTs. We suggest that GISTs of epithelioid cell morphology are tested for SDHB immunohistochemically. In case of negative SDHB staining in GISTs, Carney-Stratakis syndrome or Carney triad should be considered and appropriate clinical surveillance should be instituted.
Carney triad can be (rarely) associated with germline succinate dehydrogenase defects
European Journal of Human Genetics, 2015
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.
18F-FDG PET/CT “hepatic superscan” in incomplete Carney’s triad
Srpski arhiv za celokupno lekarstvo
Introduction. Carney triad is a rare non-hereditary condition characterized by gastrointestinal stromal tumors ? intramural mesenchymal tumors of the gastrointestinal tract with neuronal or neural crest cell origin, pulmonary chondromas, and extra-adrenal paragangliomas. The term incomplete Carney triad more precisely refers to the occurrence of at least two of these tumor types. Carney triad named after J. Aidan Carney is considered to be a specific type of multiple endocrine neoplasia. Less than 30 cases of complete and less than 100 cases of incomplete Carney triad have been reported worldwide. Carney triad primarily affects young women (mean age of onset of 20 years). Case outline. A 35-year-old female patient had an initial presentation at the National PET Center, Clinical Center of Serbia, after the gastrectomy, with multiple hepatic metastases as well as bilateral pulmonary chondromas. 18F-FDG PET/CT scan revealed the following: 1) intense 18F-FDG uptake in the liver metastat...