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Papillon-Lefèvre syndrome
This syndrome causes thickened, reddened skin on the hands and feet, combined with very early and severe gum disease that often results in tooth loss. It typically becomes apparent in early childhood.
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Overview
Papillon-Lefèvre syndrome (PLS) is a rare genetic disorder that primarily affects the skin and teeth. Individuals with PLS typically develop characteristic skin changes on the palms of their hands and soles of their feet, along with severe, early-onset periodontitis (gum disease) [PMID:33679188]. This condition is usually noticed in early childhood, often around the time a child's first teeth emerge.
PLS is considered a dermatogenetic condition, meaning it involves both skin manifestations and a genetic basis. While the skin changes can be noticeable, the severe periodontitis is a hallmark feature, leading to significant dental problems if not managed. The overall health impact can vary, but dental issues are a consistent challenge for those affected by PLS.
Symptoms & clinical features
The main symptoms of Papillon-Lefèvre syndrome involve specific skin findings and severe dental problems. Skin changes typically appear during the first few years of life, often presenting as redness and thickening (keratosis) on the palms and soles. These areas can sometimes become scaly or dry, and in some cases, fissures (cracks) may develop, which can be painful or prone to infection.
Simultaneously, affected individuals experience aggressive periodontitis. This gum disease starts early, often with the eruption of milk teeth (deciduous teeth), and progresses rapidly. Gums become inflamed, bleed easily, and teeth may loosen and fall out prematurely. This process often repeats with the permanent teeth. Without effective management, individuals with PLS may lose most of their teeth by adolescence [PMID:33679188]. Other less common symptoms can include infections, particularly skin abscesses, and in some cases, an increased susceptibility to certain infections.
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Affected organs
The primary organs affected in Papillon-Lefèvre syndrome are the skin, specifically the palms of the hands and soles of the feet, and the structures supporting the teeth, known as the periodontium. The periodontium includes the gums, alveolar bone, and other tissues that hold teeth in place. The severe inflammation and destruction of these tissues lead to early tooth loss.
Less commonly, the immune system may also be subtly affected, contributing to the recurrent infections seen in some individuals. Bone density might also be atypical in some cases, though this is not a universal feature of the syndrome.
Risks & severity
Papillon-Lefèvre syndrome is a condition with a spectrum of severity, though dental manifestations are consistently severe. The rapid progression of periodontitis usually begins in early childhood, often before the age of five, leading to significant tooth loss. The skin changes, while generally not life-threatening, can cause discomfort, pain, and impact daily activities due to cracking or infection. The lifetime risk of developing these symptoms is very high for individuals with PLS.
While severe, the condition is not typically considered life-limiting. However, the chronic nature of the dental problems requires ongoing, intensive care throughout life. Some studies suggest a potential, though unconfirmed, increased risk for certain infections or other health issues in a small number of patients [PMID:33679188].
Genetic causes
Papillon-Lefèvre syndrome is caused by pathogenic variants in the CTSC gene. This gene provides instructions for making an enzyme called cathepsin C. Cathepsin C is a type of protein that plays a crucial role in immune function, particularly within certain immune cells like neutrophils, which are important for fighting infections.
Normally, cathepsin C helps activate other enzymes involved in the immune response and may also have a role in the normal development of the skin and gums. When pathogenic variants occur in CTSC, the enzyme's activity is significantly reduced or absent. This impaired function of cathepsin C is thought to contribute to the uncontrolled inflammation seen in the gums and the specific skin changes characteristic of PLS [PMID:29661608].
- CTSC cathepsin C
Inheritance pattern
Papillon-Lefèvre syndrome is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic variant in the CTSC gene - one from each parent - to develop the condition.
If a person inherits only one copy of the pathogenic variant, they are called a carrier. Carriers typically do not show symptoms of PLS. When two carriers have children, there is a 25% chance with each pregnancy that their child will inherit two pathogenic variants and be affected by the syndrome, a 50% chance the child will be an unaffected carrier, and a 25% chance the child will inherit two typical copies of the gene and be unaffected and not a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Papillon-Lefèvre syndrome is typically suspected based on the characteristic clinical features: severe early-onset periodontitis and specific skin lesions on the palms and soles. A clinical geneticist or dermatologist, often in conjunction with a specialist dentist (periodontist), will evaluate the symptoms. Confirmation of the diagnosis is made through genetic testing, which identifies pathogenic variants in the CTSC gene.
In the UK, referrals for genetic testing for conditions like PLS are generally made through a specialist, such as a consultant paediatrician, dermatologist, or clinical geneticist. These tests are performed within the NHS Genomic Medicine Service, often using an R-code, such as R253 for inherited skin disorders or R203 for rare genetic disorders. Genetic counselling is an integral part of the diagnostic process, providing information and support to families.
Management & lifestyle
Management of Papillon-Lefèvre syndrome focuses on symptom control and preventing complications, particularly severe tooth loss and skin infections. A multidisciplinary team approach is essential, typically involving dentists specialising in periodontology, dermatologists, and clinical geneticists.
For the dental issues, aggressive and ongoing periodontal treatment is crucial, including regular cleaning, antibiotics to manage infections, and sometimes tooth extractions. In some cases, bone grafting procedures or dental implants may be considered later in life, though success can be challenging due to the underlying condition. Skin management involves topical treatments for hyperkeratosis (thickened skin) and emollients to prevent dryness and cracking, along with antibiotics for any skin infections. Genetic counsellors can also provide support and information regarding the genetic basis and inheritance pattern of the syndrome.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like Papillon-Lefèvre syndrome typically enter the NHS Genomic Medicine Service pathway. This often begins with a referral from a GP or specialist to a clinical genetics service. Clinical geneticists and specialist teams use their expertise to assess symptoms and may recommend genetic testing, which can confirm a diagnosis by identifying specific genetic changes, such as those in the CTSC gene. Genetic testing is supported by relevant NHS R-codes where applicable.
Genetic counsellors are key members of this team, offering essential support, explaining inheritance patterns, and helping families understand the implications of a genetic diagnosis. They also provide information about managing the condition and connecting with patient support networks.
Frequently asked questions
What is the typical age that Papillon-Lefèvre syndrome symptoms first appear?
Symptoms of Papillon-Lefèvre syndrome typically begin in early childhood, often between one and five years of age. This usually coincides with the eruption of the first set of teeth, and the skin changes on the palms and soles also become noticeable around this time.
Can Papillon-Lefèvre syndrome be cured?
Currently, there is no cure for Papillon-Lefèvre syndrome as it is a genetic condition. Management focuses on treating the symptoms, particularly through intensive dental care and skin treatments, to improve quality of life and prevent complications. Regular follow-ups with specialists are essential.
Does Papillon-Lefèvre syndrome affect other parts of the body?
While Papillon-Lefèvre syndrome primarily affects the skin of the palms and soles and the gums and teeth, some individuals may experience other issues. These can include a predisposition to certain infections due to the role of the CTSC gene in immune function. However, major organ involvement is not typical.
Is Papillon-Lefèvre syndrome very rare?
Yes, Papillon-Lefèvre syndrome is considered a very rare condition. It is estimated to affect approximately one in a million people worldwide. Due to its rarity, diagnosis can sometimes be delayed.
What kind of dental care is needed for Papillon-Lefèvre syndrome?
Dental care for Papillon-Lefèvre syndrome is extensive and lifelong. It involves frequent visits to a periodontist for professional cleaning, treatments for gum inflammation, antibiotics to control bacterial infections, and potentially extractions of severely affected teeth. Maintaining excellent oral hygiene at home is also vital.