cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis

Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis is an ultra-rare condition that primarily affects the heart, skin, hair, and teeth. It is caused by changes in the DSP gene, which encodes the protein desmoplakin that is critical for cell adhesion and tissue integrity. This condition is inherited in an autosomal dominant pattern, meaning a single altered copy of the gene can lead to disease. Because it affects fewer than 1 in 1,000,000 individuals, it is considered very rare.

The clinical presentation is marked by a distinctive set of features. Every affected individual shows palmoplantar keratoderma, ventricular tachycardia, dilated cardiomyopathy, hyperkeratosis, tooth agenesis, and woolly hair. In addition, some individuals may experience less common features such as leukonychia, fragile nails, ichthyosis, pruritus, nail dystrophy, and episodes of syncope. Not all individuals experience all features, and severity varies considerably, reflecting the variable expressivity of the condition.

This condition is caused by pathogenic variants in the DSP gene, which encodes desmoplakin, a protein essential for maintaining the structural integrity of cells in tissues such as the heart and skin. It is inherited in an autosomal dominant pattern, meaning that a single defective copy of the gene can lead to the development of the condition. While the core features are consistently observed, there is variable expressivity where the presence and severity of some additional symptoms can differ among affected individuals. Genetic counseling is recommended to help families understand the inheritance implications and options for family planning. Associated genes include DSP.