Novel compound heterozygous mutations in the desmoplakin gene cause hair shaft abnormalities and culminate in lethal cardiomyopathy

Summary A 2-month-old white girl born to nonconsanguineous parents presented to the der-matology department with hair loss that had commenced a few months after birth.Although her hair loss later stabilized, it remained sparse. By the age of 2 years, shewas noted to have developed focal keratoderma over pressure points of the soles.Aged 5 years, she was admitted to hospital with a chest infection, and investigationsat that point revealed that she had a dilated cardiomyopathy. Subsequent geneticinvestigations identified compound heterozygous mutations in the 3′ end of the des-moplakin (DSP) gene (7567delAAGA and 6577G>A), explaining the cardiocutaneousphenotype.Desmosomes are cell–cell adhesion junctions prominentin the epidermis and myocardium. The most abundantdesmosomal proteins are the desmoplakins (DSPs).Homozygous and heterozygous DSP gene mutationshave been reported, which can phenotypically appearas palmoplantar keratoderma (PPK), hair-shaftabnormalities (woolly hair or variable alopecia) andvarious subtypes of cardiomyopathy.