A Compound Heterozygous Cathepsin C Mutations Causing Phenotypical Papillion Lafevre/Haim-Munk Syndrome: A Case Report and Review of WES Findings.

Abstract

Introduction: Cathepsin C (CTSC), a lysosomal cysteine protease, acts as a primary activator of several critical immune enzymes. Mutations in CTSC can cause a variety of conditions, primarily Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS), both rare autosomal recessive palmoplantar keratoderma (PPK) diseases.

Case report: We report the case of a 24-year-old female patient. Her past medical history revealed an undiagnosed condition associated with symptoms of thick, dry, and cracked skin. Additionally, she is of Myanmar heritage and has shared a family history of similar symptoms. The patient was referred to a dermatologist for further evaluation and genetic sequencing to confirm the diagnosis. Whole-exome sequencing (WES) revealed two heterozygous compound variants in the CTSC gene.

Discussion: The report highlighted the clinical findings relevant to CTSC's genetic standpoint regarding the mutational indications of PLS and HMS. These diseases are allelic and share clinical features of PPK, including early-onset periodontal deterioration and early tooth loss. These diseases are lifelong and management is usually palliative and quality-focused.

Conclusion: The WES confirmed a likely Haim-Munk syndrome diagnosis from compound heterozygous CTSC variants. This aligns with severe PPK and early tooth loss, underscoring the vital need for genetic counseling and further family testing. For dental practitioners, early identification of patients with suspected Papillon-Lefèvre or Haim-Munk syndrome is essential to enable timely genetic referral, appropriate prosthetic rehabilitation, and multidisciplinary management.