Papillon–Lefèvre syndrome

Overview

Papillon–Lefèvre syndrome (PLS) is a rare inherited disorder characterized by a combination of severe periodontitis and palmoplantar keratoderma. First described by French physicians Papillon and Lefèvre in the 1920s, the syndrome typically manifests in early childhood with inflammation and degeneration of the gums and early loss of both primary and permanent teeth. Simultaneously, affected individuals develop thickened, scaly skin on the palms of the hands and soles of the feet. PLS is an autosomal recessive condition and is associated with immune dysfunction that predisposes individuals to aggressive oral infections. Although rare, early diagnosis and multidisciplinary care can significantly improve outcomes and preserve quality of life.

Causes

Papillon–Lefèvre syndrome is caused by mutations in the CTSC gene, which encodes the enzyme cathepsin C. This enzyme plays a key role in activating various immune system proteins, especially those in neutrophils, which are white blood cells involved in fighting infections. When cathepsin C is non-functional or deficient due to genetic mutations, the body’s ability to combat infections—particularly in the periodontal tissues—is impaired. This leads to the characteristic severe gum disease seen in PLS. The disorder is inherited in an autosomal recessive pattern, meaning a person must inherit two defective copies of the gene (one from each parent) to develop the condition.

Symptoms

Symptoms of Papillon–Lefèvre syndrome usually begin between the ages of 1 and 5. The most prominent features affect the skin and oral cavity:

Oral Symptoms

• Severe periodontitis: Inflammation and destruction of the gums and supporting structures of the teeth begin soon after the eruption of primary teeth.

• Premature tooth loss: Both baby teeth and permanent teeth are usually lost early, often by the early teenage years.

• Halitosis (bad breath): Due to severe gum infections.

• Oral pain and swelling: Common during periods of active infection.

Skin Symptoms

• Palmoplantar keratoderma: Thickening and hardening of the skin on the palms of the hands and soles of the feet, often starting in infancy or early childhood.

• Cracking and fissuring: The thickened skin may crack, become painful, and be prone to secondary infections.

• Extension of lesions: In some cases, the hyperkeratosis may extend to the knees, elbows, and other body parts.

Other Features

• Increased susceptibility to infections: Due to impaired immune function, patients may experience recurrent skin or systemic infections.

• Possible intracranial calcifications: Rare cases have reported calcifications in the brain, though this is not a universal feature.

Diagnosis

Diagnosis of Papillon–Lefèvre syndrome is based on a combination of clinical features, family history, and genetic testing:

• Clinical examination: Early-onset periodontitis and palmoplantar keratoderma in a child strongly suggest PLS, especially in the absence of other systemic disease.

• Dental history: Dentists often play a key role in suspecting the syndrome due to early and severe gum disease.

• Skin biopsy: May show nonspecific signs of hyperkeratosis but is not usually required for diagnosis.

• Genetic testing: Identification of biallelic mutations in the CTSC gene confirms the diagnosis.

• Radiographic imaging: X-rays of the jaw may reveal bone loss and changes in the alveolar bone due to periodontitis.

Treatment

Treatment of Papillon–Lefèvre syndrome is challenging and requires a multidisciplinary approach involving dermatologists, dentists, periodontists, and pediatricians. The goals are to control infections, preserve dental function, and manage skin symptoms:

• Dental management:

  • Frequent professional cleanings and rigorous oral hygiene to slow periodontal disease.

  • Systemic antibiotics during active infections may reduce bacterial load.

  • Extraction of severely affected teeth followed by prosthetic rehabilitation such as dentures or dental implants when feasible.

• Dermatological care:

  • Topical keratolytics (e.g., salicylic acid or urea-based creams) to soften thickened skin.

  • Topical or systemic retinoids (e.g., acitretin) may help control keratoderma in severe cases.

• Infection prevention: Good hygiene and prompt treatment of infections are essential.

• Genetic counseling: Should be offered to affected families to discuss recurrence risk in future pregnancies.

Prognosis

With early diagnosis and appropriate treatment, many complications of Papillon–Lefèvre syndrome can be managed, though the condition remains chronic. Most individuals lose their teeth prematurely due to uncontrollable periodontitis, which can impact nutrition and quality of life. However, prosthetic dental solutions can help restore function. Skin symptoms can usually be controlled with topical therapies and retinoids, though recurrences are common. Life expectancy is generally normal, but the psychosocial impact of the disease, particularly due to cosmetic and dental issues can be significant. Ongoing care and support are essential for optimizing outcomes and improving quality of life.