BG03 The first case of Haim–Munk syndrome in the UK

Abstract

Abstract Haim–Munk syndrome (HMS) and Papillon–Lefevre syndrome (PLS) are rare, autosomal recessive palmoplantar keratodermas (PPKs) characterized by PPK and periodontal inflammation. They are phenotypic variants of clinically related syndromes caused by homozygous or compound heterozygous mutations in cathepsin C (CTSC) on chromosome 11q14. Specific features of HMS include pes planus, radiographic deformity of the fingers, arachnodactyly, acro-osteolysis and onychogryphosis. In contrast, PLS can be associated with neurological disorders, calcification of the dura mater, hyperhidrosis and susceptibility to infection. Fewer than 100 cases of HMS have been reported, the majority of which have come from the Cochin region of India. We describe the case of a phenotypic presentation of HMS, with a novel mutation in CTSC. To our knowledge, this is the first case of HMS in the UK. The patient was a 14-year-old male, born in Gujarat, India, to consanguineous, healthy parents. He migrated to the UK in his early teens and was referred for a specialist opinion of symptoms of ichthyosis and PPK, which had been present from the age of 8 years. He was treated with acitretin in India, before moving to the UK. Physical examination revealed transgradient PPK, generalized mild ichthyosis, periodontal inflammation, dystrophic fingernails and toenails, and marked deformities of the fingers, including contractures, subluxation and swan-neck deformities, with a degree of arthritis. Bilateral hand radiographs showed slender, long bones, with extension/flexion deformities at several sites but no erosions. Laboratory investigations revealed low iron, folate and vitamin D levels. Based on the clinical and radiographic findings, a diagnosis of HMS was made. The patient was continued on acitretin, soap substitutes, regular emollients, iron, folate and vitamin D supplementation and referred to occupational therapy for hand splinting. Next-generation sequencing identified an autosomal recessive, homozygous c.901G>A (p.Gly301Ser) variant of CTSC. A total of 75 mutations, in a diverse range of ethnic groups, have been reported in CTSC; the majority (97%) is reported in PLS. The variant seen in our patient has previously been reported in PLS; however, to our knowledge, it has not been associated with the HMS phenotype. This case details the first homozygous c.901G>A CTSC variant in a patient with HMS. To date, the genotype–phenotype correlations in PLS and HMS have not been established, largely due to the rarity of these conditions. This report adds to existing literature and expands on the understanding of clinical findings associated with CTSC mutations.