Clouston syndrome is an autosomal dominant inherited disorder characterized by the leading symptoms of hyperkeratosis, nail dystrophy and alopecia. The syndrome is caused by mutations in the GJB6 gene, which encodes the gap junction protein connexin-30.
The first description of this rare disease was made in 1929 by the Canadian physician H.R. Clouston. The exact prevalence is not known, probably the syndrome is not always diagnosed. The most regular symptom is nail changes, which may be present at birth or in early neonatal life. Typically, the nails are thickened, grow slowly, and are brittle, often hyperconvex, discolored, and striated. Additional symptoms include microonychia, onycholysis, and recurrent paronychia with loss of nails. Another characteristic symptom is total to partial, often progressive alopecia, which is present at birth or occurs in infancy/childhood. The remaining main hair grows slowly and is sparse, fine and brittle. Eyebrows, eyelashes and body hair are often sparse as well. Palmoplantar hyperkeratosis does not occur regularly. When present, it usually begins in childhood and tends to worsen with advancing age. In some patients, hyperkeratosis and hyperpigmentation also develop over joints and bony prominences.
Casuistry: Example from everyday clinical practice
A research team from the dermatology department of the University Hospital of Lausanne described the following patient example from a family with Canadian roots: the 4-year-old girl has brittle, brittle hair and hypotrichosis, as well as hyperkeratotic nails and slightly reddened and thickened palms and soles. In the father, palmoplantar lesions extend to the borders of the feet and hands, Achilles tendon, and ankles. If cracks form, pain occurs when walking. Similar problems have occurred over at least four generations. Some of the family members were bald, while others had more palmoplantar keratoderma and nail abnormalities, and others showed few symptoms. Molecular genetic testing revealed a heterozygous mutation in the GJB6 gene. Skin biopsy showed hyperkeratosis but little inflammatory change, which was confirmed by the absence of an inflammatory signature of transcriptomic analyses.
Treatment options
To date, only symptomatic treatment options exist for Clouston syndrome. These include topical keratolytics, oral retinoids, and orthopedic devices to reduce pressure. In an animal model using Cx30A88V/A88V adult mice, an antibody against connexin 30 resulted in a decrease in gap junction hemichannel activity. According to Morren et al. this may be a new treatment approach. Connexins are a family of transmembrane proteins that form gap junctions in cells and allow the direct exchange of molecules up to about 1 kDa in size between neighboring cells.
Sources:
- Orphanet, www.orpha.net,(last accessed Feb 09, 2023).
- Morren MA, et al: Clouston syndrome: a rare form of ectodermal dysplasia. Poster 15, abstract volume, SGDV Annual Meeting, 9-11.2022.
DERMATOLOGIE PRAXIS 2023; 33(1): 37 (published 2/14/2013, ahead of print).
