Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity. Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP, although its mechanism of action is unknown. We describe a series of eight XP patients, six of whom were given oral isotretinoin. The NK cell activity was not affected by low-dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell function, at the same time as producing a reduction in the frequency of development of skin cancers. Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation.

Ectodermal dysplasias (EDs) comprise a large clinically and etiologically heterogeneous group of genetic disorders characterized by abnormalities in tissues derived from the embryonic ectoderm. Controversy exists over which syndromes should be classified as EDs and which should be excluded from the classification. The challenge will be to balance comprehensiveness within the classification with usability and accessibility so that the benefits truly serve the needs of researchers, health-care providers, and ultimately the individuals and families directly affected by EDs. The overarching goal of the Second International Conference was to develop a consensus on EDs classifications, with the ultimate goal of creating a system that integrates clinical and molecular knowledge, using an interactive Internet-based database that clinicians, researchers, and laymen can use. The Conference, brought together a group of experts from around the world, including a diverse health-care providers, researchers, patient advocate representatives, and administrators. The Conference was modeled after the 2008 conference, with plenary sessions, scientific updates, and small group discussions. Based on the present clinical knowledge, new molecular advances and both coupled with new bioinformatics developments, the participants agree to develop a multiaxis system approach for the classification of EDs. The multiaxis approach will include a clinical/phenotype axis, a genebased axis, and a functional/pathways axis. The significance of the conference outcomes includes, a new classification approach that will foster a better understanding of EDs, open new fields of research and develop a nosologic approach that may have broad implications for classifying other hereditary conditions. Ó 2014 Wiley Periodicals, Inc. 2482 INTRODUCTIONEctodermal dysplasias (EDs) comprise a large clinically and etiologically heterogeneous group of genetic disorders that are characterized by abnormalities in tissues derived from the embryonic ectoderm. As of July 2013, at least 186 distinct pathological clinical conditions have been recognized and defined as EDs. They all share common features: anomalies in hair, teeth, nails, and sweat glands, but most are associated with anomalies in other organs and systems. Some complex phenotypes are now explained in the light of the molecular causative defects involving, for instance, widely expressed proteins with essential roles in control of cell cycle progression, in replication and/or DNA repair. The EDs are extremely variable with significant clinical overlap between many EDs, making them difficult to diagnose precisely. Indeed, controversy exists over which syndromes should be classified as EDs and which should be excluded from such a classification. The EDs have historically been diagnosed and classified based upon clinical manifestations. However, during the last few years, new advances in the molecular basis and biological functions have allowed researchers to explore the unique molecular pathways involved in the ...