Papillon-Lefevre Syndrome

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OMIM 57 245000 Disease Ontology 12 DOID:3389 MeSH 44 D010214 NCIt 50 C84992 SNOMED-CT 68 40158001 Orphanet 59 ORPHA678 MESH via Orphanet 45 D010214

ICD10 via Orphanet 34 Q82.8 UMLS via Orphanet 74 C0030360 MedGen 42 C0030360 KEGG 37 H00274 SNOMED-CT via HPO 69 258211005 66383009 706885006 271607001 29966009 62250003 17944005 203522001 30425001 28899001 402815007 2092003 372244006 122483006 39034005 234974002 42756003 87065009 27916005 103605005 271760008 285305004 47002008 more UMLS 73 C0030360

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 678Disease definitionPapillon-Lefèvre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.EpidemiologyThe 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 descriptionDiffuse 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.EtiologyPLS 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 methodsDiagnosis 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 diagnosisDifferential 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 diagnosisAntenatal diagnosis is theoretically possible but has never been reported.Genetic counselingTransmission 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 treatmentTreatment 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.PrognosisDespite 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.

MalaCards based summary : Papillon-Lefevre Syndrome, also known as papillon-lefevre disease, is related to platelet groups--pl system and lateral sclerosis. An important gene associated with Papillon-Lefevre Syndrome is CTSC (Cathepsin C), and among its related pathways/superpathways are Lysosome and IL12-mediated signaling events. The drugs Contraceptive Agents and Contraceptives, Oral have been mentioned in the context of this disorder. Affiliated tissues include skin, bone and testes, and related phenotypes are cerebral calcification and recurrent respiratory infections

OMIM : ⁵⁷ Papillion-Lefevre syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, periodontitis, and premature loss of dentition (summary by Lefevre et al., 2001). (245000)

UniProtKB/Swiss-Prot : ⁷⁵ Papillon-Lefevre syndrome: An autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees.

Wikipedia : ⁷⁶ Papillon–Lefèvre syndrome (PLS), also known as palmoplantar keratoderma with periodontitis, is an... more...

Clinical features from OMIM:

245000

Search NIH Clinical Center for Papillon-Lefevre Syndrome

Search GEO for disease gene expression data for Papillon-Lefevre Syndrome.