Cardiomyopathy with alopecia and palmoplantar keratoderma (CAPK) is caused by a JUP mutation

Abstract

Inherited desmosomal cardiocutaneous syndromes are characterized by the quartet of woolly hair, palmoplantar keratoderma (PPK), skin fragility and cardiac abnormalities, which are caused by mutations in genes coding for desmosomal proteins. We describe a previously unrecognized autosomal recessive syndrome in a family with arrhythmogenic right ventricular cardiomyopathy associated with alopecia and PPK (named CAPK). Genetic investigation of the family led us to find a homozygous disease-causing mutation, p.R265H, in JUP which encodes plakoglobin, a well-described member of the desmosome complex. This study expands the clinical spectrum of disorders associated with germline mutations affecting desmosomal proteins by describing a novel phenotype.

Combination of palmoplantar keratoderma and hair shaft anomalies, the warning signal of severe arrhythmogenic cardiomyopathy: a systematic review on genetic desmosomal diseases

“…The Naxos phenotype is characterised by diffuse PPK, woolly hair and classic right dominant arrhythmogenic cardiomyopathy in all reported patients. Two Turkish related patients carried a homozygous missense mutation (c.794G>A, exon 4) 15. Their phenotype was close to Naxos syndrome and characterised by the association of cardiomyopathy (classic right dominant arrhythmogenic cardiomyopathy), alopecia (atrichia) and PPK (CAPK syndrome).…”

Genetic skin diseases related to desmosomes and corneodesmosomes

“…Heterozygous carriers usually have no skin or hair abnormalities, but up to 25% have heart involvement. A novel cardiocutaneous disease caused by the homozygous missense mutation in JUP was found in patients with ARCV, PPK and alopecia [16]. Clinically, it is similar to Naxos disease, but with alopecia rather than woolly hair.…”

When Rare Illuminates Common: How Cardiocutaneous Syndromes Transformed Our Perspective on Arrhythmogenic Cardiomyopathy

“…There are many other documented cases of cardiocutaneous syndromes secondary to homozygous, double heterozygous or compound heterozygous mutations in plakoglobin, desmoplakin and desmocollin (Asimaki et al, 2009;Delmar & McKenna, 2010;Bolling & Jonkman, 2009;Alcalai et al, 2003;Erken et al, 2011;Uzumcu et al, 2006). Woolly hair is a prevalent feature, but alopecia has also been observed (Asimaki et al, 2009;Bolling et al, 2010;Erken et al, 2011).…”

“…Woolly hair is a prevalent feature, but alopecia has also been observed (Asimaki et al, 2009;Bolling et al, 2010;Erken et al, 2011). Skin involvement ranges from extremely dry skin to the well-known palmoplantar keratoderma; vesicular lesions at the extremities, knees, palms and soles; and lethal acantholytic epidermolysis bullosa (Bolling & Jonkman, 2009;Delmar & McKenna, 2010).…”