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Haim-Munk syndrome (HMS) and Papillon-Lefevre syndrome (PLS) are phenotypic variants of palmoplantar keratoderma (PPK) with progressive early-onset periodontitis and dental caries. HMS and PLS have been associated with homozygous or compound heterozygous mutations in the lysosomal protease gene Cathepsin C (CTSC). There have been only a few documented cases of CTSC mutations in patients from South-East Asia. We report the clinical findings of two Cambodian brothers who presented with diffuse, demarcated PPK with transgrediens extending to the elbows and knees, as well as pachyonychia and dental caries. Arachnodactyly and periodontitis were also found in the older brother. Next-generation sequencing unveiled a homozygous missense variant in CTSC (NM_001814.5: c.1337AC: p.(Asp446Ala)) in both brothers. Both parents were heterozygous for the variant, while an unaffected older brother was homozygous for the wild-type allele. Our study adds to the spectrum of mutations and associated clinical presentations for this rare genodermatosis., (© 2019 Wiley Periodicals, Inc.)

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects mediated by these proteases in inflammatory/auto-immune disorders. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome (PLS). The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objective: Papillon-Lefèvre Syndrome (PLS) is a rare autosomal recessive hereditary disease (MIM245000). The syndrome is characterized by palmoplantar keratoderma and early onset periodontitis, caused by CTSC gene mutation. The mutation in CTSC previously reported is mainly point mutations. Large deletion in the CTSC gene has not yet been reported., Material and Methods: We collected 5 mL peripheral blood from a patient with PLS and her family members and used the direct sequencing method to perform CTSC bidirectional sequencing. We also used FISH to analyze the approximate locations of the ends of the missing fragment and then determined the fragment sequence through direct sequencing., Results: The result demonstrated that the patient have a 110 kb deletion (Chr11: 88032292: 88142997(NC_000011)) combined with a nonsense mutation (Gln182Ter) in this gene., Conclusion: Our study reveals a compound mutation consisting of a large deletion and a nonsense mutation, which provides a new insight in the mutation type of CTSC gene., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder of keratinization caused by homozygous mutations in the gene encoding lysosomal protease cathepsin C (CTSC). It is clinically characterized by transgredient palmoplantar keratoderma (PPK) and periodontitis. A 15-year-old boy presenting with PPK from the age of 6 months and late-onset periodontitis that began at the age of 12 years is described. Mutation analysis revealed a homozygous nonsense mutation (p.Y304X) in exon 7 of the CTSC gene. Late-onset periodontitis in a patient with Papillon-Lefèvre syndrome is a rare phenotypic variation., (© 2015 Wiley Periodicals, Inc.)

The Papillon-Lefèvre syndrome (PLS) is a rare, autosomal recessive disease that manifests with palmoplantar keratoderma and destructive periodontitis resulting in early onset periodontal breakdown in deciduous and permanent dentition. Management of this condition is difficult. Here we report one 11-year-old consanguineous Muslim boy suffering from PLS. After failing to get any benefit from methotrexate, three cycles of acitretin, each for 2 months, were given 1 month apart. In each cycle, acitretin (25 mg) was given every other day. At the end of the third cycle, treatment was stopped for 4 months to observe the extent of relapse. Thereafter, acitretin (25 mg) was given twice weekly for 4 months and then the patient was followed up for 1 year. Treatment with acitretin resulted in excellent improvement of periodontitis, increase in the alveolar bone height, and periodontal attachment. Improvement remained stable at the end of 1-year follow-up. There was excellent (>75%) improvement in keratoderma at the end of active therapy. Mild worsening of palmoplantar keratoderma was noticed whenever the drug was stopped. It improved when the drug was restarted. Other areas remained stable. At the end of 1-year follow-up, good improvement (50%) in palmoplantar keratoderma was achieved., (© 2014 Wiley Periodicals, Inc.)

Background: Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor., Aim: We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood., Methods: To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients., Results: Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37., Conclusions: Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease.

Papillon-Lefèvre syndrome (PLS) is a rare inherited palmoplantar keratoderma (PPK) that is associated with progressive gingivitis and recurrent pyodermas. We present a case exhibiting classic features of this autosomal-recessive condition and review the current understanding of its pathophysiology, diagnosis, and treatment. Additionally, a review of pertinent transgredient PPKs is undertaken, with key and distinguishing features of each syndrome highlighted.

Papillon-Lefevre syndrome is a rare autosomal recessive genetic disorder. The clinical manifestations include palmer planter hyperkeratosis with precocious progressive periodontal disease that results in premature exfoliation of primary and permanent dentitions. Patients are often edentulous at an early age. This is a case report of prosthodontic rehabilitation of a 15-year-old girl with Papillon-Lefevre syndrome.

Papillon-Lefevre syndrome is a very rare syndrome of autosomal recessive inheritance characterized by palmar-plantar hyperkeratosis and early onset of a severe destructive periodontitis, leading to premature loss of both primary and permanent dentitions. Various etiopathogenic factors are associated with the syndrome but a recent report has suggested that the condition is linked to mutations of the cathepsin C gene. Two cases of Papillon-Lefevre syndrome in the same family, having all of the characteristic features, are presented. An 11-year-old girl and a 9-year-old boy presented with the complaints of loose teeth. Both expressed hyperkeratosis of palms, soles, and knees. Severe generalized periodontal destruction, with mobility of teeth, was evident on intraoral examination; orthopantomograph examination showed severe generalized loss of alveolar bone in both the patients.

Papillon Lefevre syndrome (PLS) is a rare autosomal recessive disorder, which is characterized by palmar-plantar hyperkeratosis, periodontitis, and premature loss of dentition. We report a 16 years old girl with PLS. The patient presented at 08 years of age with complaints of corn on the feet and hands, and failure to thrive. On examination, her upper primarily canines were loose, she had severe periodontitis, eruption of permanent teeth, diffuse eritematous and hyperkeratotic palms and soles that suggested the syndrome. During the follow-up, the patient was diagnosed to have congenital hepatic fibrosis (CHF) when she was 16 years old, while she was being investigated for the etiology of her splenomegaly and pancytopenia. We report a patient with PLS associated with CHF, an association that has not been previously described. Abbreviations-HbsAg: Hepatitis B virus surface antigen, Anti Hbs: Antibody against Hepatitis B surface antigen, Anti Hbc IgM: Antibody against Hepatitis B cor antigen immunglobulin M, Anti dsDNA: Antibody against double stranded deoksiribonucleic acid, Anti HCV: Antibody against Hepatit C virus, Anti HIV: Antibody against human immun deficiency virus, AST: Aspartat amino transferase, ALT: Alanin amino transferase, Gamma-GT: Gamma glutamyl transferase, LDH: Lactate dehydrogenase & MRI: Magnetic resonance imaging.

Systemic diseases affecting the host response as primary immunodeficiencies or secondary defects caused by lack of nutrients or changes in the local tissues are very often accompanied by early-onset prepubertal periodontitis. Local treatment in combination with systemic antibiotics may in milder forms improve the situation, but in many cases the success is questionable and premature loss of teeth occurs. Since the genetic basis of many of the diseases has been identified, future developments permit the correction of at least some of these defects by gene therapy.

The aim of the present study was to evaluate the salivary secretion rate and composition in a group of 16 children and young adults (6-27 years) with Papillon-Lefèvre Syndrome (PLS), and to compare the findings with a group (n = 16) of healthy controls. Unstimulated and stimulated whole saliva was collected at least 2 h after meals and the secretion rate determined. The stimulated saliva was assessed for buffer capacity, total protein, peroxidase and hexosamine, while the unstimulated samples were evaluated for total protein, lysozyme, thiocyanate, lactoferrin and salivary IgA. Both the unstimulated (p < 0.01) and stimulated (p < 0.05) saliva secretion rates were significantly lower among the PLS patients compared with the controls. Furthermore salivary buffer capacity was significantly (p < 0.01) lower in the PLS patients. The total protein content in saliva was comparatively high in the study group, while the concentrations of immunoglobulins and non-immunoglobulins were within normal ranges. When calculating the output of the assessed antimicrobial factors, the mean peroxidase level in stimulated whole saliva was found to be significantly (p < 0.01) lower in the PLS patients than in the healthy controls. In conclusion, the present study indicates an impaired water secretion and a somewhat altered saliva gland function in children and young adults with PLS.

Numerous systemic syndromes with different aetiopathogenetic and clinical features are constantly accompanied by function changes in neutrophil polymorphoanucleates and, particularly, in their chemotactic properties. The function they perform, namely impeding the invasion of the organism on the part of aggressive external factors, cannot therefore be implemented. These patients are thus abnormally susceptible to infections and present severe periodontal disease with high frequency.

Recently we had the opportunity to examine and follow up over a period of 2 years an unusual case of Papillon-Lefèvre syndrome (PLS). A 10 year old boy exhibited all symptoms typical of PLS except periodontitis and premature loss of deciduous teeth. The present report aimed at studying the functional capacity of his neutrophilic granulocytes. It integrates clinical observations, histopathological findings and results of in vitro tests. The bioptic material examined included one gingival biopsy, extracted teeth, suppurative material discharged from periodontal pockets, pus emanating from a mucosal abscess, and peripheral blood leucocytes. The neutrophils were sampled on two separate occasions in two independent laboratories and tested for a variety of functions, i.e. motility, random and directional locomotion (chemotaxis), phagocytosis, membrane potential depolarization, oxygen consumption, NBT reduction, and intracellular killing of bacteria and fungi. Findings and test data indicated that in this case of PLS, neutrophilic granulocytes behaved normally with respect to all these functions including margination in blood vessels, emigration, phagocytosis of a broad range of bacteria, degranulation of lysosomes, and intracellular destruction. The data imply that factors other than neutrophil defects may be responsible for rapidly destructive periodontitis in cases where PLS is not associated with an increased susceptibility to infection.

A 9-year-old girl was treated for the periodontal component of Papillon-Lefèvre syndrome, an autosomal recessive disease characterized by palmarplantar hyperkeratosis and premature loss of teeth. Initially, the patient was found to have a polymorphonuclear leukocyte chemotactic dysfunction, defective leukocyte adherence, and deep periodontal pockets harboring presumptive periodontopathic bacteria. After unsuccessful treatment with combined mechanical therapy and 2 different antibiotics, all of the patient's erupted teeth were extracted in an attempt to minimize the chance of infection of teeth yet to erupt. At age 16 years, the now-erupted teeth have normal gingiva and crevice depths, radiographs show no evidence of periodontal pathology, no periodontopathic bacteria are detected in gingival crevices, and leukocyte function is normal.

The Papillon-Lefévre syndrome (PLS) is an autosomal recessive trait characterized by diffuse transgredient palmar-plantar keratosis (PPK) and premature loss of both the deciduous and permanent teeth. In most cases, the PPK is noted within the first 3 years of life. The periodontal lesions begin shortly after the start of both the primary and the permanent dentitions. The teeth are affected in the order of their eruption, exhibiting inflammation of the periodontal tissue, bleeding of the gums, pocket formation, loosening, and finally spontaneous exfoliation without showing definite signs of root resorption. After an edentulous interval, the same process begins anew shortly after the second dentition. Ectopic intracranial calcifications, mental retardation, and increased susceptibility to infections have often been seen in PLS patients and may thus be regarded as facultative signs.

An unusual case of Papillon-Lefevre syndrome is reported. The 10-year-old boy exhibited all symptoms typical of this disease except premature loss of primary teeth. The patient's past history, his status at first examination, an initial successful treatment phase, the efforts made at long-term maintenance and the eventual treatment failure are described. The bacterial plaque covering subgingival root surfaces was examined by scanning electron microscopy, and the histopathologic alterations of glossy, glaring red gingival tissue halos are described and discussed with respect to the pathogenesis of periodontitis associated with this syndrome.