Background —Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease of unknown etiology that causes arrhythmias, heart failure, and sudden death. Diagnosis can be difficult, and this hampers investigation of its molecular basis. Forms of ARVC in which gene penetrance and disease expression are greater should facilitate genetic study. We undertook a clinical and genetic investigation of Naxos disease, originally described by Protonotarios in 1986. This disease constitutes the triad of ARVC, diffuse nonepidermolytic palmoplantar keratoderma, and woolly hair. Methods and Results —We evaluated the population of Naxos, Greece, to identify probands, which was followed by family screening. Twenty-one affected persons from 9 families of 150 persons were identified. Linkage analysis was performed with microsatellite markers. The disease locus mapped to 17q21. A peak 2-point LOD score of 3.62 at θ=0.0 was found with a marker within intron 4 of the keratin 9 gene, a member of the type I (acidic) keratin family. A preserved homozygous disease haplotype was identified. Haplotype analysis delimited the disease interval. Conclusions —Hair and skin abnormalities were found to be reliable markers of subsequent heart disease. This suggests the presence of a single mutant gene with novel cardiac, skin, and hair function or two or more tightly linked disease genes. Recessive inheritance of Naxos disease and a founder effect were demonstrated. Identification of a fully informative genetic marker linked to the disease and uncommon in the background population may be of use as a test to identify disease gene carriers.

Botulinum toxin type A injections are an effective and well-tolerated treatment for hyperhidrosis. This paper proposes a positioning of this treatment along with current established treatments, and highlights the role of botulinum toxin type A as a valuable therapy for the treatment of hyperhidrosis.

Our preliminary experience of 4 cases of ulcerative PG indicates that split skin grafts have a role to play in its management. The ultimate cosmetic result is considered to be superior to allowing the wound to heal by secondary intention. To limit the risk of pathergy developing, our experience suggests a role for prolonged courses of immunosuppressive therapy. The most effective dose and duration of immunosuppressive therapy in patients with PG treated with split skin grafts remains to be determined. A controlled study would be of benefit to compare it with other current treatment options.