Dutch Multidisciplinary Guideline on Dupuytren Disease.

Purpose: To provide a comprehensive, evidence-based overview of the treatment for Dupuytren disease, specifically needle techniques, radiotherapy, primary conservative therapy, surgery, lipofilling, operative arthrolysis, salvage techniques, and the postoperative protocol and to make clinical recommendations for health care practitioners and patients. Methods: Comprehensive multidisciplinary guideline process funded by the Quality Foundation of the Dutch Federation of Medical Specialists. This process included a development, commentary, and authorization phase. Patients participated in every phase. Multiple databases and existing guidelines up to August 2020 were searched. Studies on Dupuytren disease were considered eligible. Specific eligibility criteria were described per module. To appraise the certainty of the evidence, reviewers extracted data, assessed the risk of bias, and used the Grading of Recommendations Assessment, Development and Evaluation method, where applicable. Important considerations were as follows: patient values and preferences, costs, acceptability of other stakeholders, and feasibility of implementation. Recommendations were made based on the evidence from the literature and the considerations. The primary and secondary outcome measures were defined per module based on the input of patients obtained in collaboration with the Netherlands Patient Federation and health care providers from different professions. Results: The following 8 specific modules were completed for Dupuytren disease: (1) needle techniques, (2) radiotherapy, (3) primary conservative therapy, (4) surgery, (5) lipofilling, (6) operative arthrolysis, (7) salvage techniques, and (8) the postoperative protocol. Conclusions: Our Dutch multidisciplinary guideline on Dupuytren disease provides 8 modules developed according to the standards of the Dutch Federation of Medical Specialists. Evidence-based recommendations for clinical practice are provided for needle techniques, radiotherapy, primary conservative therapy, surgery, lipofilling, operative arthrolysis, salvage techniques, and the postoperative protocol. This guideline can assist health care providers and patients in clinical practice. Type of study/level of evidence: Systematic review/I-II.

Phenotypic variability in a family with capillary malformations caused by a mutation in the RASA1 gene.

Hereditary capillary malformations are known to be caused by mutations in the RASA1 gene. The associated phenotype is still subject of debate. The purpose of this study was to conduct a RASA1 mutation analysis in the family that led to the initial discovery of the 5q locus, and to delineate the associated phenotype. A novel truncating mutation was identified in all clinically affected individuals and in none of the unaffected members. The associated phenotype was widely variable; all individuals had multifocal CM with at least one area of high flow. Various additional features were observed, some previously reported and others novel, including limb overgrowth, varicosities, possible lymphatic malformations, localized hyperhidrosis and exercise induced redness. The cause of this wide intramutational phenotypic variability remains to be elucidated.

Familial clustering of giant congenital melanocytic nevi.

Giant congenital melanocytic nevus (GCMN) is an infrequently occurring congenital malformation. GCMN generally occurs in isolation but rare familial occurrence points to a genetic background. We present two cases of familial GCMN: one with two affected siblings and another with two affected double second cousins. Familial occurrence of GCMN reported in literature is reviewed and an overview of the embryology and proliferation given, illustrating the plethora of factors that might lead to GCMN formation. The pattern of inheritance is likely not Mendelian and discordance in identical twins and the segmental distribution of lesions suggest a post-zygotic mutation. A polygenic paradominant inheritance best explains the clinically observed transmission pattern. Candidate genes include those influencing neural crest development and melanocyte proliferation.