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The article presents a case study of three white patients with Brooke–Spiegler syndrome (BSS) who were initially diagnosed both clinically and histopathologically. Topics include mutation analysis of the cylindromatosis (CYLD) gene, which revealed three splice site mutations and assessment of the expression of CYLD in normal human epidermal keratinocytes (NHEK), leucocytes and peripheral blood mononuclear cells (PBMC) by quantitative reverse transcriptase (qRT)-PCR.

Smit DL, Mensenkamp AR, Badeloe S, Breuning MH, Simon MEH, van Spaendonck KY, Aalfs CM, Post JG, Shanley S, Krapels IPC, Hoefsloot LH, van Moorselaar RJA, Starink TM, Bayley J-P, Frank J, van Steensel MAM, Menko FH. Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis. Heterozygous fumarate hydratase ( FH) germline mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome characterized by multiple cutaneous piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer. The main objective of our study was to evaluate clinical and genetic data from families suspected of HLRCC on a nationwide level. All families referred for FH mutation analysis in the Netherlands were assessed. We performed FH sequence analysis and multiplex ligation-dependent probe amplification. Families with similar FH mutations were examined for haplotype sharing. In 14 out of 33 families, we identified 11 different pathogenic FH germline mutations, including 4 novel mutations and 1 whole-gene deletion. Clinical data were available for 35 FH mutation carriers. Cutaneous leiomyomas were present in all FH mutation carriers older than 40 years of age. Eleven out of 21 female FH mutation carriers underwent surgical treatment for symptomatic uterine leiomyomas at an average of 35 years. Two FH mutation carriers had papillary type 2 renal cancer and Wilms' tumour, respectively. We evaluated the relevance of our findings for clinical practice and have proposed clinical diagnostic criteria, indications for FH mutation analysis and recommendations for management. [ABSTRACT FROM AUTHOR]

The article discusses the implications of the Wingless (WNT) pathway towards the development of odonto-onycho-dermal dysplasia (OODD). It states that OODD is caused by the mutation of the WNT10A gene which is characterized by keratoderma, nail dystrophy and abnormal teeth. It presents the findings of a study conducted by the authors which revealed evidence for phenotypic heterogenicity associated with WNT10A genetic mutations.

Background Erysipelas is a common skin infection that is usually caused by β-haemolytic group A streptococci. After having had erysipelas in an extremity, a significant percentage of patients develops persistent swelling or suffers from recurrent erysipelas. We hypothesize that in cases of erysipelas without a clear precipitating agent, subclinical pre-existing congenital or acquired disturbances in the function of the lymphatic system are present. The persistent swelling after erysipelas is then most likely caused by lymphoedema. Objectives We designed a study to examine if erysipelas of unknown origin is associated with a pre-existent insufficiency of the lymphatic system. If our hypothesis is correct, patients with erysipelas of unkown cause without previously evident lymphoedema should have evidence of disturbed lymphatic transport in the unaffected extremity. Methods A prospective study, in which lymphoscintigraphy of both legs was performed in patients 4 months after presenting with an episode of erysipelas only in one leg. No patient had any known risk factor for erysipelas, such as diabetes mellitus, chronic venous insufficiency or clinical signs of lymphoedema. Lymphoscintigraphy was performed in 40 patients by subcutaneous injection of Tc-99m-labelled human serum albumin in the first web space of both feet. After 30 and 120 min, quantitative and qualitative scans were performed using a computerized gamma camera. During the lymphoscintigraphy, the patients performed a standardized exercise programme. Lymph drainage was quantified as the percentage uptake of Tc-99m-labelled human serum albumin in the groin nodes at 2 h after injection. Groin uptake of < 15% is pathological; uptake between 15–20% is defined as borderline, and uptake of > 20% as normal. Results The mean ± SD percentage uptake in the groin nodes in the affected limbs was 9·6 ± 8·5% vs. 12·1% ± 8·9% in the nonaffected limbs. The mean paired difference in uptake between the nonaffected vs. affected side was 2·5% (95% confidence interval 1·1–3·9%). This indicates that lymphatic drainage in the nonaffected limb was only slightly better than in the affected limb despite the infectious event in the latter. Of 33 patients with objective impairment of lymph drainage in the affected limb, 26 (79%) also had impaired lymph drainage in the nonaffected limb. Agreement in qualitative measurements between affected and nonaffected leg was less pronounced: 21 patients had abnormal qualitative results in the affected leg of whom nine also had impairment of the nonaffected leg (43%). Conclusions Erysipelas is often presumed to be purely infectious in origin, with a high rate of recurrence and a risk of persistent swelling due to secondary lymphoedema. In this study, we show that patients presenting with a first episode of erysipelas often have signs of pre-existing lymphatic impairment in the other, clinically nonaffected, leg. This means that subclinical lymphatic dysfunction of both legs may be an important predisposing factor. Therefore, we recommend that treatment of erysipelas should focus not only on the infection but also on the lymphological aspects, and long-standing treatment for lymphoedema is essential in order to prevent recurrence of erysipelas and aggravation of the pre-existing lymphatic impairment. Our study may change the clinical and therapeutic approach to erysipelas as well as our understanding of its aetiology. [ABSTRACT FROM AUTHOR]

Acquired hypertrichosis lanugo-type or hypertrichosis lanuginosa acquisita (HLA) is often associated with metabolic and endocrine disorders and use of certain drugs. The occurrence of HLA with malignancy was first noted in 1865, and it has since been described in 56 patients as a paraneoplastic syndrome both in women and in men. Sometimes HLA occurs concurrent with acanthosis nigricans, papillary hypertrophy of the tongue, and glossitis. The predominance of female cases is striking. Malignancy-associated HLA seems to occur especially in the age group 40–70 years. In women with HLA the most frequent malignancy is colorectal cancer, followed in order by lung cancer and breast cancer; in men lung cancer is the malignancy most frequently associated with HLA, followed by colorectal cancer. In 3 years we saw 10 patients with HLA, in whom the malignancy was usually metastasized. Only one patient had local disease; after removal of the primary tumour it took 2 years before the lanugo hair recurred. The aetiology of the syndrome is not clear: no specific hormonal or biochemical abnormalities have been identified as yet. The difference between hirsutism and lanugo-type hypertrichosis is discussed. It is stressed that the appearance of lanugo-type hypertrichosis in body areas previously perceived by patients as ‘hairless’ is highly indicative of internal malignancy. [ABSTRACT FROM AUTHOR]

Background Conradi–Hünermann–Happle syndrome [X-linked dominant chondrodysplasia punctata type 2 (CDPX2); MIM no. 302960] is an X-linked dominant disorder of cholesterol metabolism that causes a wide spectrum of skeletal abnormalities and linear ichthyosiform skin lesions. Mosaicism is probably responsible for the variability of the phenotype. Objectives To describe new mutations in patients with variable manifestations of the disease. Methods We studied three patients with CDPX2. We performed mutation analysis of the EBP (formerly known as CDPX2) gene and gas chromatography–mass spectroscopy on serum of two patients. Results We found two novel (3G→T and 419-422delTTCT) and one known mutation in the EBP gene. We demonstrated the presence of increased levels of dehydrocholesterol and 8(9)-cholestenol in the two patients with new mutations, confirming the diagnosis of CDPX2 and strongly suggesting that the mutations are indeed pathogenic. One patient had a very mild phenotype, presenting with linear alopecia and a mild symmetrical epiphyseal dysplasia. X-inactivation studies in peripheral blood of all patients showed skewing in only the most severely affected patient. Conclusions The strong phenotypic variability in our patients suggests that there is no clear genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

Recent insights into the cell biology of the epidermis and its appendages are transforming our understanding of the pathogenesis of basal cell carcinoma (BCC). The significant progress that has been made warrants a comprehensive review of the molecular and cellular pathology of BCC. The items addressed include environmental and genetic risk factors, the biology of the putative precursor cell(s), and the contribution of aberrations in processes such as apoptosis, cell proliferation, differentiation and signalling to carcinogenesis. Furthermore, established and novel treatment modalities are discussed with particular attention to future biological approaches. [ABSTRACT FROM AUTHOR]

We describe a Dutch man suffering from a previously undescribed erythrokeratoderma associated with palmoplantar keratoderma and circular constrictions of the fingers. No mutations were identified in the genes encoding loricrin, connexin 26, 30, 30.3, 31 and 31.1, and ARS/complex B. There are some similarities between the disorder described here and other palmoplantar keratodermas and erythrokeratodermas, but assignment to a particular disease category is not possible. Hence we propose that we have delineated a novel type of keratoderma. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing the Bazex-Dupré-Christol syndrome and its relationship with chromosome Xq25-27.1.

The article presents a case study of a woman who had progressive cutaneous and uterine leiomyoma. Her medical history reveals that she was also diagnosed at the age of 2 years with single Wilms tumor, and was treated with surgery and chemotherapy. It notes that the development of Wilms tumor is closely related to fumarate hydratase (FH) gene dysfunction. It says that the occurrence of uterine leiomyoma with kidney cancer suggests hereditary leiomyomatosis and renal cell cancer.

A letter to the editor is presented discussing the potential of defects in DNA mismatch to signify an early-onset basal cell carcinoma.

The article presents a case study of a girl having mild phenotype of congenital ichthyosis and hypotrichosis which is linked to a new mutation in CDLN1. The hair of the patient was extremenly brittle and she did not have eyelashes or eyebrows. Her mother reported that enamel of her milk teeth was previously dysplastic.

A letter to the editor is presented in response to the article about the missense mutation in KRT14 which cause a Naegeli-Franceschetti-Jadasshn syndrome/dermatopathia igmentosa reticularis (NFJS/DPR).

A letter to the editor is presented in response to the article "Nail Dystrophy in Focal Acral Hyperkeratosis: A Distinctive Feature," by Z. Khamaysi, R. Bergman and E. Sprecher in the previous issue of the journal.

Presents a letter to the editor related to the novel syndrome of hypotrichosis, acro-osteolysis, palmoplantar keratoderma, peridontis, and onychogryphosis.

Background: Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo-associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the 'comedo switch'. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG-associated skin disorders., Results: In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin-like growth factor 1 receptors; peroxisome proliferator-activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis., Conclusions: Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne., (© 2019 British Association of Dermatologists.)

Background: Acne vulgaris is a highly prevalent inflammatory skin disorder with a complex pathogenesis, characterized by comedones, papules, pustules and nodules. Familial preponderance clearly indicates a genetic basis for acne vulgaris, but until recently solid genetic associations were lacking., Results: The advent of high-resolution genotyping array technologies has allowed for large-scale studies with both family-based and cross-sectional designs. These studies have revealed genetic loci encompassing genes that could be active in biological pathways and processes underlying acne vulgaris. However, specific functional consequences of those variants remain elusive. In parallel, investigations into rare disorders and syndromes that incorporate features of acne or acne-like lesions have recently accelerated our understanding of disease pathogenesis. The genes revealed by these rare disorders highlight mechanisms cardinal for pilosebaceous biology and therefore anchor our insights from genetic association studies for acne vulgaris., Conclusions: The next phase of research will require more in-depth mechanistic investigations of loci and genes implicated in acne phenotypes to define the key molecular players driving the disorder. Concurrently, new treatments for acne vulgaris could be developed by dissecting the candidate molecular pathways to identify druggable targets., (© 2019 British Association of Dermatologists.)