Primary focal hyperhidrosis in a new family not linked to known loci

Background: Primary focal hyperhidrosis (PFH) is a disabling disorder. A first locus has been mapped in families with only palmar involvement, raising the question whether other unknown genes are responsible for more diffuse phenotypes. Objective: We investigated a PFH family with a new phenotype, providing evidence that PFH is a clinically and genetically heterogeneous condition. Methods: Family members were examined by autonomic tests, skin biopsy and genetic analysis, and followed up for 4 years. Results: Age at onset was early, involving the axillae, palms and soles. Affected members had dysautonomic features also at onset. Cardiovascular dysautonomia was present in affected and unaffected members. Skin biopsy revealed impairment of intraepidermal nerve fibers and reduced innervation of sweat glands. There was no linkage to PFH and aquaporin-5 loci. Conclusion: This pedigree may serve as a basis for identifying a novel unmapped gene. Skin biopsy and cardiovascular autonomic tests provide important additions to the characterization of PFH.