Cowden syndrome: a critical review of the clinical literature.
ABSTRACT Cowden syndrome (CS) is a multi-system disease involving hamartomatous overgrowth of tissues of all three embryonic origins and increased risks for thyroid, breast and possibly other cancers. Benign breast, thyroid, uterine and skin lesions are also common. Approximately 80% of patients with CS have an identifiable germline mutation in the PTEN gene. The majority of the existing data on the frequencies of component clinical features have been obtained from compilations of case reports in the literature, many of which predate the establishment in 1996 of consensus diagnostic criteria. Many of these reports also suffer from ascertainment bias which emphasized the dermatologic features of the disease. This paper presents an overview of Cowden syndrome focusing on a critical evaluation of the major literature on the component cancers, benign features, and molecular findings in CS, noting the limitations of the published data.
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ABSTRACT: Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by overgrowth, macrocephaly, distinctive facial features and variable degree of intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising from 5q35 microdeletions, point mutations, and partial gene deletions, accounts for a majority of patients with SoS. Recently, mutations and possible pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have been reported in patients with Sotos-like overgrowth features. To estimate the frequency of NSD1 defects in the Brazilian SoS population and possibly reveal other genes implicated in the etiopathogenesis of this syndrome, we collected a cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS, and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent probe amplification and mutational screening analyses. We identified a classical NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a less severe presentation of SoS phenotype, which did not include pre- and postnatal overgrowth. For the first time, our study implies PTEN in the pathogenesis of SoS and further emphasizes the existence of ethno-geographical differences in NSD1 molecular alterations between patients with SoS from Europe/North America (70-93%) and those from South America (10-19%).Molecular syndromology 01/2015; 6(1). DOI:10.1159/000370169
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ABSTRACT: We present a patient with newly diagnosed Cowden syndrome and congestive myeloradiculopathy secondary to spinal dural arteriovenous fistula (SDAVF). This patient illustrates the difficulties that can be encountered in diagnosing SDAVF and emphasises the need to pursue the diagnosis in the appropriate clinical setting, as treatment can lead to significant neurological improvement. To our knowledge this is also the first reported case of an association between Cowden syndrome and SDAVF.Journal of Clinical Neuroscience 10/2014; 22(2). DOI:10.1016/j.jocn.2014.07.023 · 1.32 Impact Factor
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ABSTRACT: Cowden syndrome (CS) is an autosomal dominant disorder characterized by presence of multiple hamartomas, and other benign and malignant abnormalities of the breasts, skin, thyroid, endometrium, gastrointestinal tract, and central nervous system. Hamartomas are benign, developmentally disorganized tumors that can develop in any of the above mentioned organs. The presence of massive calcifications in the breasts in very young women is an indication to perform a breast MRI to exclude a neoplasm since, like in the current case report, presence of breast calcifications may obscure a neoplasm. Although fibrocystic disease and cooccurrence of fibrocystic disease and breast cancer are much more common than CS, the presence of massive calcifications in the breasts of very young women should elicit the possibility of an underlying genetic disease. Furthermore, breast cancer and macrocephaly are considered major criteria for the diagnosis of CS and the combination of both is enough to establish the clinical diagnosis of this entity. Fibrocystic disease of the breasts and multinodular goiter are minor criteria. Family history is also important for the diagnosis of (any) hereditary disease.07/2012; 2012:638725. DOI:10.1155/2012/638725