Rare Dermatology News

Disease Profile

Papillon Lefevre syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Childhood

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ICD-10

Q82.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hyperkeratosis palmoplantaris with periodontosis; Keratoris palmoplantaris with periodontopathia; Palmar-plantar hyperkeratosis and concomitant periodontal destruction;

Categories

Congenital and Genetic Diseases; Immune System Diseases; Metabolic disorders;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 678

Definition
Papillon-Lefèvre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.

Epidemiology
The prevalence is estimated between 1/250,000 and 1/1,000,000 individuals. The male to female ratio is 1:1. PLS is found in all ethnic groups.

Clinical description
Diffuse palmoplantar keratoderma (see this term) with erythematous plaques develops between the first and fourth years of life, with the soles being usually more severely affected than the palms. Psoriasiform hyperkeratosis can overflow onto the dorsal surfaces of the hands and feet (transgredient spread) and, less frequently, lesions can be seen on the limbs (knees, elbows). Skin lesions are followed by intense gingivitis that rapidly progresses into periodontitis with alveolar bone lysis and early loss of primary dentition. The skin lesions are aggravated by cold and during episodes of severe periodontitis. During childhood, the phenomenon of periodontal disease recurs with rapid loss of permanent dentition. Cases of PLS with mild and/or late-onset periodontal disease have been reported occasionally. PLS is accompanied, in half of the patients, by enhanced susceptibility to cutaneous and systemic infections (furunculosis, skin abscesses, pyoderma, hidradenitis suppurativa (see this term), respiratory tract infection...). Patients may also present with malodorous hyperhidrosis, follicular hyperkeratosis, nail dystrophy or dural calcifications. The association of PLS with malignant melanoma or squamous cell carcinoma has been reported in very rare occasions.

Etiology
PLS is due to mutations in the CTSC gene (11q14.2) that codes for cathepsin C (also known as dipeptidyl peptidase I), a lysosomal protease playing a role in epidermal differentiation and desquamation and in activation of serine proteases expressed in cells of the immune system. CTSC mutations lead to an almost total loss of cathepsin C activity which seems to result in susceptibility to specific virulent pathogens. It is also suggested that other immune-mediated deficiencies in the host defense mechanism could be involved in the pathogenesis of PLS.

Diagnostic methods
Diagnosis is based on clinical signs. Dental radiography shows atrophy of the alveolar bone. Neutrophil function tests reveal anomalies of chemotaxis and phagocytosis by polymorphonuclear leukocytes. Skin biopsy shows hyperkeratosis with focal parakeratosis, moderate perivascular infiltration, hypergranulosis, and acanthosis. Biochemical analysis reveals a loss of CTSC activity. Diagnosis is confirmed by genetic testing.

Differential diagnosis
Differential diagnosis includes two rare disorders that are allelic variants of PLS, Haim-Munk syndrome (see this term) and prepubertal/aggressive periodontitis. Other diseases with similar dermatologic features include localized epidermolytic palmoplantar keratoderma (Vörner), mal de Meleda, Howel-Evans syndrome, transgrediens et progrediens palmoplantar keratoderma (Greither's disease) (see these terms), and keratosis punctata.

Antenatal diagnosis
Antenatal diagnosis is theoretically possible but has never been reported.

Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to the parents of an affected individual informing them of the 25% chance their offspring has of inheriting the disease causing mutation.

Management and treatment
Treatment is based on oral retinoids which attenuate the palmoplantar keratoderma and slow the alveolar bone lysis. Antibiotics, along with oral hygiene and use of mouth rinses, are also recommended for slowing the progression of periodontitis. Ultimately, primary or remaining teeth are extracted and are replaced by dental implants. Antibiotherapy is also used in the treatment of recurrent infections. Etretinate (a synthetic retinoid) shows promising results in the treatment of PLS.

Prognosis
Despite meticulous dental care, all patients eventually become edentulous at the beginning of adulthood. Life expectancy is normal.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal fingernail morphology
Abnormal fingernails
Abnormality of the fingernails

[ more ]

0001231
Atrophy of alveolar ridges
Shrinking of gum ridges
0006308
Gingivitis
Inflamed gums
Red and swollen gums

[ more ]

0000230
Palmoplantar hyperkeratosis
Thickening of the outer layer of the skin of the palms and soles
0000972
Palmoplantar keratoderma
Thickening of palms and soles
0000982
Premature loss of primary teeth
Early loss of baby teeth
Premature loss of baby teeth

[ more ]

0006323
Pustule
Pimple
0200039
Reduced number of teeth
Decreased tooth count
0009804
Severe periodontitis
0000166
30%-79% of people have these symptoms
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Chronic furunculosis
0011132
Nail dystrophy
Poor nail formation
0008404
Recurrent cutaneous abscess formation
0100838
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
5%-29% of people have these symptoms
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

0001166
Cigarette-paper scars
'cigarette paper scarring'
Cigarette paper scarring

[ more ]

0001073
Generalized hirsutism
Excessive hairiness over body
0002230
Hypertrichosis
0000998
Hypopigmented skin patches
Patchy loss of skin color
0001053
Liver abscess
0100523
Melanoma
0002861
Osteolysis
Breakdown of bone
0002797
Sparse body hair
0002231
Squamous cell carcinoma
0002860
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Choroid plexus calcification
0006960
Premature loss of teeth
Early tooth loss
Loss of teeth
Premature teeth loss
Premature tooth loss

[ more ]

0006480

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Papillon Lefevre syndrome. Click on the link to view a sample search on this topic.