Atypical case of Naxos syndrome with anhidrosis from India

Abstract

Naxos syndrome, known as Naxos disease, is a rare genetic disorder characterized by arrhythmogenic right ventricular cardiomyopathy (ARVC), woolly hair, and palmoplantar keratoderma. First described on the Greek island of Naxos, it involves mutations in genes such as desmoplakin, plakoglobin, desmocollin-2, and SRC-interacting protein (SIP), crucial for cardiac and skin integrity. Management necessitates a multidisciplinary approach involving cardiology, dermatology, and genetic counseling. A 3-year-old girl from a third-degree consanguineous marriage exhibited sparse hair, absent sweating, delayed tooth eruption, and increased skin fragility. Clinical examination revealed erosions in periorificial areas, periorbital wrinkling, abnormal dentition, and generalized xerosis with mild hyperkeratosis of the palms and soles. Clinical differentials included Anhidrotic ectodermal dysplasia and McGrath syndrome. However, whole exome sequencing identified a homozygous JUP gene mutation (exon 5), indicating Naxos syndrome, albeit lacking classical palmoplantar keratoderma and wooly hair. Cardiac evaluation is deferred until the child reaches 10 years due to known cardiac abnormalities in Naxos typically manifesting in the 2nd decade. This case deviates from classical Naxos syndrome by lacking typical palmoplantar keratoderma or woolly hair, where hair sparsity can also occur. Notably, skin fragility, unreported in Naxos literature, and anhidrosis accentuate its uniqueness. Emphasizing genetic counseling, especially in consanguineous families, this case contributes to the limited literature on pediatric Naxos syndrome in India. It signifies the first reported child with atypical Naxos syndrome associated with anhidrosis and skin fragility, accentuating the need for broader awareness and research in such presentations.