Sexually Transmitted Trichophyton mentagrophytes Genotype VII Infection among Men Who Have Sex with Men.

Transmission of dermatophytes, especially Trichophyton mentagrophytes genotype VII, during sexual intercourse has been recently reported. We report 13 such cases in France. All patients were male; 12 were men who have sex with men. Our findings suggest sexual transmission of this pathogen within a specific population, men who have sex with men.

[Genetics of complex and syndromic palmoplantar keratoderma]. / Génétique des kératodermies palmoplantaires complexes et syndromiques.

Palmoplantar keratodermas (PPK) comprise a heterogenous group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Hereditary PPKs can be classified into 3 groups: 1) isolated non-syndromic PPKs; 2) complex non-syndromic PPKs associated with other ectodermal defects; and 3) syndromic PPKs associated with extracutaneous manifestations. All types of inheritance have been observed: autosomal dominant, autosomal recessive, X-linked recessive, and mitochondrial. Some of these disorders are restricted to geographic isolates. This review describes the different genetic causes of hereditary syndromic and complex PPKs for which the genes have been identified. The identification of pathogenic variants has consequences in terms of genetic counseling, appropriate medical care and follow-up, especially for PPKs predisposing to hearing loss, cardiomyopathies, benign tumors or carcinomas. In addition, the development of targeted therapies based on pathophysiology of disorders should allow a more effective treatment of these conditions in the near future.

Severe Phenotype in Patients with Large Deletions of NF1.

Complete deletion of the NF1 gene is identified in 5-10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described "classic" NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.

Porokeratosis Plantaris, Palmaris et Disseminata Caused by Con- genital Pathogenic Variants in the MVD Gene and Loss of Hetero-zygosity in Affected Skin.

Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known. This study analysed a cohort of 4 patients with linear porokeratosis and 3 patients with porokeratosis plantaris, palmaris et disseminata, and performed mutation analyses of DNA extracted from blood samples and skin biopsies. All of the study patients carried the heterozygous germline variant c.70+5G>A in the MVD gene. Loss of heterozygosity due to a second hit mutation was found in affected skin of 3 patients with linear porokeratosis and 2 patients with porokeratosis plantaris, palmaris et disseminata. These results suggest that porokeratosis plantaris, palmaris et disseminata shares the same pathogenetic mechanism as other porokeratosis subtypes and belongs to the phenotypic spectrum of MVD-associated porokeratosis.

Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4.

Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa-Like Domain-Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype-phenotype correlations.

Alitretinoin reduces erythema in inherited ichthyosis.

BACKGROUND: Acitretin is the main retinoid used to treat severe inherited ichthyosis. Alternatives may be considered if it results ineffective or there are side-effects, or for women of childbearing age. Our objective is evaluation of the effects and tolerance of alitretinoin. An observational retrospective multicentric study was designed to analyse patients with inherited ichthyosis treated by alitretinoin. RESULTS: A total of 13 patients were included, 11 of whom were receiving acitretin at inclusion. The main reason for switching to alitretinoin was a desire for pregnancy, but also because of side-effects or unsatisfactory efficacy. Starting dose was 10 mg/day, increased to 20 or 30 mg/day. Alitretinoin seemed to be more effective than acitretin at reducing erythema, but was less effective at reducing scaling or hyperkeratosis. Global efficacy was considered low for two patients, moderate for nine, and high for two. Treatment was well-tolerated, except for one patient who presented with benign intracranial hypertension leading to discontinuation of treatment. CONCLUSIONS: Alitretinoin may be suitable for hereditary ichthyosis with prominent erythema, especially for women of childbearing age.

[Eccrine porocarcinoma with Bowenoid changes: a challenging diagnosis of adnexal neoplasm]. / Porocarcinome eccrine bowénoïde : un carcinome annexiel de diagnostic difficile.

Eccrine porocarcinoma is a rare malignant sweat gland tumor, representing less than 0.01% of all cutaneous neoplasms, with eccrin differentiation. Its acrosynringeal origin and physiopathology still remain discussed. The prognosis of this carcinoma is held to be poor with a significant risk of lymph node metastasis and local recurrence. Also, this not specific tumor can be a challenging histological diagnosis, in particular, in Bowenoid variant. We report a case of Bowenoid and keratinizing variant of eccrine porocarcinoma of the left ring finger with pejorative evolution and initial diagnosis of infiltrating squamous cell carcinoma arising in Bowen's disease. The knowledge of these patterns and identification of eccrine differentiation of the tumor are essential for the diagnosis and for adapted therapeutic care.