Clinical and genetic characterisation of palmoplantar keratoderma

Research output: ThesisPh.D. thesis

Abstract

Palmoplantar keratoderma is a disease characterised by hardened and thickened skin on palms and soles. In addition to often eye-catching skin changes, the disease can be accompanied by pain, sweat and an unpleasant odour. Given the lack of effective treatment options, the disease can have a great impact on patients’ daily lives.

Palmoplantar keratoderma is most often isolated to hands and feet, but may also be part of more widespread skin conditions or part of syndromes with a wide range of associated conditions ranging from deafness to severe heart disease. Consequently, patients represent a very heterogeneous group, where clinical classification, as well as decisions on which patients should be offered additional examinations, can be difficult. With advancements in genetic testing and a growing knowledge about various hereditary causes of the disease, the potential to enhance the understanding of the condition is improving. The objective of this thesis is to increase the insights on the clinical symptoms and the genetic causes of palmoplantar keratoderma though three studies.

The aim of Study I was to improve knowledge about the clinical and genetic characteristics of patients with palmoplantar keratoderma in Denmark. A cohort of 142 patients from 76 families was prospectively established. Each participant was extensively described clinically and systematically genetically evaluated. A genetic diagnosis was identified in 80 percent of the families, which demonstrated the value of genetic testing to sub-diagnose patients with palmoplantar keratoderma.

In Study II, we investigated 20 patients from the Region of Southern Denmark, all diagnosed with punctate palmoplantar keratoderma and the variant AAGAB c.370C>T, p.(Arg124Ter). Haplotype analysis confirmed the variant to be a founder variant with an estimated age of 12.1 generations.

In Study III, we conducted a systematic review to explore the evidence regarding a potential association between punctate palmoplantar keratoderma type 1 and the risk of malignancy. Our review showed huge methodological challenges within the existing literature, including the studies that for decades have suggested an association. Based on this, we found it highly questionable whether these patients should be offered malignancy screening, but better and more well-designed studies than the existing studies in the literature are necessary to definitely accept or reject an association.
Translated title of the contributionKlinisk og genetisk karakterisering af palmoplantar keratodermi
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
Supervisors/Advisors
  • Ousager, Lilian Bomme, Principal supervisor
  • Bygum, Anette, Co-supervisor
  • Brusgaard, Klaus, Co-supervisor
Date of defence26. Apr 2024
Publisher
DOIs
Publication statusPublished - 2. Apr 2024

Note re. dissertation

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