Random Dermatology MCQ - Papillon-Lefèvre syndrome

An 8-year-old child is brought to the clinic with severe, foul-smelling inflammation of the gums and loose teeth. The parents report that the child's primary teeth became loose and fell out prematurely around age 4. On examination, there is well-demarcated, thick, yellowish, hyperkeratotic plaques on the palms and soles extending to the dorsal surfaces. What is the most likely genetic defect and the serious associated risk in this condition?

A. Mutation in the cathepsin C (CTSC) gene; severe, early-onset periodontitis leading to loss of both primary and permanent dentition.
B. Mutation in the connexin 26 (GJB2) gene; sensorineural hearing loss.
C. Mutation in the keratin 9 (KRT9) gene; progressive palmoplantar keratoderma.
D. Mutation in the plakophilin 1 (PKP1) gene; skin fragility and woolly hair.
E. Mutation in the desmoplakin (DSP) gene; cardiomyopathy.

Correct Answer: A. Mutation in the cathepsin C (CTSC) gene; severe, early-onset periodontitis leading to loss of both primary and permanent dentition.

Answer and Explanation

The correct answer is A. This question describes the classic tetrad of Papillon-Lefèvre syndrome (PLS): 1) Palmoplantar keratoderma (PPK) that is transgredient (extends to dorsum of hands/feet), 2) Premature loss of primary teeth, 3) Premature loss of permanent teeth due to severe periodontitis, and 4) Calcification of the dura mater (clinically silent). The condition is caused by mutations in the cathepsin C (CTSC) gene, which encodes a lysosomal protease important for immune cell function and epithelial integrity. The periodontitis is aggressive and destructive, leading to loss of the entire dentition if not managed extremely aggressively.

Why the Other Options are Incorrect:

• B. Mutation in the connexin 26 (GJB2) gene: This causes syndromes of palmoplantar keratoderma with deafness (e.g., Vohwinkel, KID syndrome), not periodontitis and premature tooth loss.

• C. Mutation in the keratin 9 (KRT9) gene: This causes epidermolytic palmoplantar keratoderma (Vörner type), a non-syndromic, isolated PPK without any dental or systemic associations.

• D. Mutation in the plakophilin 1 (PKP1) gene: This causes ectodermal dysplasia-skin fragility syndrome, characterized by skin fragility, hair abnormalities, and keratoderma, but not the specific dental findings of PLS.

• E. Mutation in the desmoplakin (DSP) gene: This causes cardiocutaneous syndromes like Carvajal or Naxos disease (PPK, woolly hair, cardiomyopathy), not periodontitis.

Additional High-Yield Information for Exams:

• Pathogenesis: The CTSC mutation leads to loss of cathepsin C enzyme activity. This impairs neutrophil serine protease activation, leading to defective phagocytic killing of bacteria, particularly Aggregatibacter actinomycetemcomitans, which drives the destructive periodontitis. It also affects epithelial desquamation, contributing to the keratoderma.

• Clinical Features:

  • Skin: Palmoplantar keratoderma typically appears between 1-4 years of age. It is diffuse, thick, and sharply demarcated, often with a red border. It extends to the dorsal surfaces (transgredient), knees, and elbows.

  • Oral: Severe periodontitis begins with the eruption of primary teeth, leading to inflammation, deep pocket formation, bone resorption, and tooth loss by age 4-5. The same process repeats with the permanent dentition, often leading to loss of all permanent teeth by mid-adolescence.

• Differential Diagnosis: The combination of transgredient PPK + premature tooth loss is pathognomonic. Other causes of early periodontitis (e.g., leukocyte adhesion deficiency, Chediak-Higashi) do not have the keratoderma. Other causes of PPK (e.g., Unna-Thost, Mal de Meleda) do not have the dental component.

• Associated Conditions & Prognosis:

  • Infections: Increased susceptibility to pyogenic skin infections (furuncles, abscesses) due to neutrophil dysfunction.

  • Dura Calcification: Asymptomatic but a characteristic radiographic finding.

  • Prognosis: The major morbidity is the complete loss of dentition, with profound functional, cosmetic, and psychological consequences. Lifespan is typically normal.

• Management & Rationale:

  • Rationale: Management is multidisciplinary and maximally aggressive to preserve the permanent dentition. The goal is to control the oral bacterial biofilm and inflammation.

  • First-line/Obligatory Dental Management: Requires a pediatric periodontist. Regimen includes:

    • Extremely rigorous oral hygiene (professional cleanings every 2-4 weeks).

    • Long-term systemic antibiotics (e.g., azithromycin) combined with topical antiseptics (chlorhexidine).

    • Early extraction of hopelessly involved teeth.

    • Full-mouth dental extraction may be necessary, followed by dentures or implants.

  • Dermatologic: Keratolytics (urea, salicylic acid), emollients, and systemic retinoids (acitretin) for severe keratoderma.

  • Genetic Counseling: Autosomal recessive inheritance.