Keratosis palmoplantaris with mutations in plakoglobin

N. Protonotarios, 1986

The very rare syndrome, first described on the Greek island of Naxos, is an autosomal recessive disorder characterized by palmoplantar keratosis, the formation of woolly hairs and an arrythmogenic right ventricular cardiomyopathy (see alsoCarvajal syndrome).

The worldwide prevalence is unknown. On Naxos it is estimated at 1:1000.

Other occurrences: Aegean Islands, Turkey, Israel, Saudi Arabia.

The cause is a mutation in the JUP gene (junctional placoglobin gene/ chromosome 17 q21), which codes for the structural protein plakoglobin, an important component of desmosomes. Thus, an essential component of cellular integrity is disturbed (Note: Desmosomes are mainly found in cells with intense mechanical stress such as epithelial cells but also in non-epithelial tissues - e.g. heart muscle - and enable mechanical cohesion by connecting the cell's own intermediate filaments with those of other cells). In cardiac tissue, the defective composition of plakoglobin leads to focal cellular destruction and reparative replacement by adipose tissue.

Patients between the ages of 2 and 7 become clinically conspicuous due to a cardiomyopathy that often occurs suddenly and can be life-threatening. Cardiomyopathy is caused by a fibrous-fatty transformation, especially of the muscles of the right ventricle, and can lead to sudden cardiac death. Dermatologically, these patients clinically impress by palmo-plantar keratoses with rhagades on the heels, as well as by curly hair or "woolly hair". Note: The syndrome of uncombed hair is a harmless, only cosmetically disturbing hair shaft anomaly(Pili trianguli et canaliculi).

The implantation of a pacemaker should take place at an early stage. Palmoplantar keratoses are treated symptomatically.

An overlapping cardiocutaneous phenotype can also be seen in other genotypes that occur due to mutations of 2 other desmosomal proteins: in keratosis palmoplantaris with mutations in desmoplakin (OMIM: 605676) and in a Naxos syndrome with mild palmoplantar keratosis and a mutation in the desmocollin-2 gene (Molho-Pessach V et al. 2015).

1. Molho-Pessach V et al (2015 Two Novel Homozygous Desmoplakin Mutations in Carvajal Syndrome. Pediatric Dermatol 32:641-646.
2. Keller DI et al. (2012)De novo heterozygous desmoplakin mutations leading to Naxos-Carvajal disease. Swiss Med Wkly 142:w13670
3. Protonotarios N. et al (1986) Cardiac abnormalities in familial palmoplantar keratosis. Br Heart Journal 56: 321-326