Case Report: Papillon-Lefèvre syndrome beyond keratoderma: two index presentations and sibling screening in two...

Papillon-Lefèvre syndrome is a rare inherited disorder classically associated with palmoplantar keratoderma and early severe periodontitis, but its clinical presentation may be broader than expected. We report four molecularly confirmed cases from two unrelated families carrying two different homozygous CTSC variants. The first index patient presented with a large iliopsoas abscess as the initial manifestation of the disease, while her monozygotic twin was diagnosed through family screening and had only mild skin and dental findings. In the second family, a 13-year-old boy had recurrent soft-tissue abscesses and palmoplantar lesions whose diagnosis was delayed for many years by a psoriasis-like presentation; his younger brother was later identified through cascade screening with a skin-limited phenotype. These cases show that PLS may present with deep infections, prolonged diagnostic delay, or mild unrecognized disease. Early molecular testing, careful dental and dermatological assessment, multifocal imaging, and systematic family screening are essential for timely diagnosis and appropriate care.