Presentation: Patient with a personal and family history of thickened palmoplantar skin

A four-year-old boy is in your clinic with marked, malodorous thickening of the skin overlying the palms and soles. Other members of the family have been affected with atypical palmoplantar skin. His parents want to know if there are any healthcare implications and if genomic testing is available.

• Testing should be considered for individuals with unexplained isolated or syndromic keratodermas, including those occurring as part of generalised skin disease.
• R166 Palmoplantar keratodermas is the most appropriate clinical indication for these presentations. It also includes genes responsible for many of the overlap presentations and syndromes – for example:
  • tylosis with oesophageal cancer (TOC), a palmoplantar keratoderma that is linked to oesophageal cancer (a diagnosis would provide the patient with access to enhanced cancer screening);
  • pathogenic variants in JUP and DSP linked to arrhythmogenic cardiomyopathy; and
  • conditions in which palmoplantar keratoderma is part of a more extensive skin phenotype, such as autosomal recessive congenital ichthyoses.
• Referrals for testing will be triaged by the genomics laboratory.
• Consider the following:
  • Testing should be targeted at those in whom a genetic or genomic diagnosis will guide management for the proband or family.
  • It is important to think about other causes of thickened palmar or plantar skin, especially when there is no family history. Other differentials, such as fungal infections, should be ruled out before requesting genomic testing.
• Note that the naming system for the keratodermas is changing: they will now be known as epidermal differentiation disorders (EDD). The new names have two parts:
  • the gene that is affected; and
  • the type of EDD – which in the case of the keratodermas will be palmoplantar epidermal differentiation disorders (pEDD).

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
• • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the tests best suits the needs of your patient or family.
• • If the presentation best fits a palmoplantar keratoderma, please consider R166 Palmoplantar keratodermas. This clinical indication includes whole exome sequencing or gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA).
• This test does not include whole genome sequencing, so you should use your local Genomic Laboratory Hub for test order and consent (record of discussion) forms.
• This test is DNA-based, and an EDTA sample (typically a purple-topped tube) is required. The sample is best stored at four degrees Celsius until it can be posted to the genomics laboratory.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Genomics England: PanelApp: Palmoplantar keratodermas

References:

• Bodemer C, Steijlen P, Mazereeuw‐Hautier J and others. ‘Treatment of hereditary palmoplantar keratoderma: A review by analysis of the literature‘. British Journal of Dermatology 2021: volume 184, issue 3, pages 393–400. DOI: 10.1111/bjd.19144
• Guerra L, Castori M, Didona D and others. ‘Hereditary palmoplantar keratodermas. Part I. Non-syndromic palmoplantar keratodermas: classification, clinical and genetic features‘. Journal of the European Academy of Dermatology Venerology 2018: volume 32, issue 5, pages 704–719. DOI: 10.1111/jdv.14902

For patients

• British Association of Dermatologists: Palmoplantar keratoderma
• Ichthyosis Support Group: Palmoplantar keratoderma