Cowden syndrome - Diagnostic skin signs

Cowden syndrome is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. The most important clinical features include carcinomas of the breast and thyroid, and hamartomatous polyps of the gastrointestinal tract. There are characteristic mucocutaneous features which allow early recognition of the disease and are generally present before internal malignancies develop. We report on a woman in whom the diagnosis of Cowden syndrome was first made after she had been treated for both breast cancer and melanoma. Copyright (C) 2001 S. KargerAG, Basel

Muir-Torre syndrome - Treatment with isotretinoin and interferon alpha-2a can prevent tumour development

Muir-Torre syndrome is a genodermatosis in which multiple internal malignancies are associated with cutaneous sebaceous tumours and kerato-acanthomas. A 57-year-old man presented with multiple sebaceous tumours, kerato-acanthomas, verrucous carcinoma of the nose, renal cell and transitional cell carcinomas of the left kidney, adenoma of the colon and a positive family history of colon carcinoma. He was treated with interferon (IFN-alpha Pa) s.c. 3 x 10(6) U three times a week along with 50 mg isotretinoin daily as well as topical isotretinoin gel. During a follow-up of 29 months, only 1 sebaceous skin tumour developed and was removed, whereas more than 30 such skin tumours had been surgically removed during the last 3 years. No evidence of internal tumour development or recurrence was found. The combination of IFN with retinoids seems to be of promise to prevent tumour development in Muir-Torre syndrome. Copyright (C) 2000 S. Karger AG, Basel

Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome

Background: Cowden syndrome (CS) or multiple hamartoma syndrome is a cancer-associated genodermatosis inherited in an autosomal dominant pattern. One of the diagnostic criteria is facial papules which are felt to be trichilemmomas, benign hair follicle tumors, which some consider to be induced by human papillomavirus (HPV). Objective: To search for HPV in skin tumors, especially trichilemmomas, from patients with CS. Methods: Skin lesions from patients with CS were classified histologically. Each tumor was then analyzed for HPV DNA by polymerase chain reaction with different primer sets; positive amplicons were typed by direct sequencing. Results: Twenty-nine biopsies from 7 patients with CS were investigated. Only 2 of 29 tumors clinically suspected of being trichilemmomas were confirmed histologically. In addition, 3 sclerotic fibromas, also typical of CS, were found, as well as 1 sebaceous hyperplasia. The other 23 lesions showed histological features of HPV-induced tumors in various stages of development. HPV DNA was found in 19 of 29 cutaneous lesions. Tumors without any histological signs of HPV induction were negative for HPV DNA. Two tumors which were histologically classified as common warts contained HPV types 27 and 28. All the 17 other HPV types belong to the group of epidermodysplasia-verruciformis-associated types. Conclusions: The majority of cutaneous lesions in CS contain HPV DNA. They may have a variety of histological patterns. Trichilemmomas are not clinically distinctive and can be difficult to identify in CS patients. Copyright (C) 2003 S. Karger AG, Basel

Dowling-Degos Disease: Case Report and Review of the Literature

Dowling-Degos disease (DDD) is an unusual pigmentary disorder usually caused by mutations in keratin 5. A 44-year-old woman in good general health presented due to the recent appearance of numerous pigmented macules on her axillary and anogenital skin. A biopsy showed lacy, finger-like epidermal extensions into the dermis which were heavily pigmented and associated with tiny cysts or dilated follicles. We view DDD as part of a spectrum of disorders which are morphologically related but vary in location and time of expression. In addition, both the clinical and histological differential diagnostic considerations are extensive. Copyright (C) 2010 S. Karger AG, Base

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Raymond Sabouraud

Effendy I. Raymond Sabouraud. In: Löser C, Plewig G, Burgdorf WHC, eds. Pantheon of dermatology : outstanding historical figures. Rev. and extended transl. of the German ed. . Berlin ; Heidelberg: Springer ; 2013: 973-976

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the &alpha;1 subunit of soluble guanylyl cyclase (&alpha;1-sGC), and CCT7 encodes CCT&eta;, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce &alpha;1-sGC as well as &beta;1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in &alpha;1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction