Papillon-Lefèvre Syndrome Research Articles

Orthodontic Treatments of Papillon-Lefevre Syndrome: Two Case Reports

Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early onset of severe destructive periodontitis causing premature loss of both deciduous and permanent dentitions at a young age. In this article two cases of patients with Papillon-Lefevre syndrome in late mixed dentition are presented. The objective of these case reports was to illustrate that under a controlled regime of periodontal treatment, orthodontic treatment is possible in patients with Papillon-Lefevre syndrome. In both cases, the deciduous dentition was lost prematurely shortly after eruption. The permanent teeth erupt without any guidance, and this can lead to loss of space, crowding, and collapse of the dental arch. The aim of the treatment was to expand the arch, create space to allow normal eruption of the permanent teeth, and stabilize the occlusion to help the patient achieve a normal facial appearance rather than the collapsed appearance caused by early extractions. KEYWORDS: Papillon-Lefevre Syndrome, Orthodontics, Mixed dentition, Case reports

Survival Rates of Dental Implants in Patients with Papillon–Lefévre Syndrome: A Systematic Review

The present review aimed to summarize and evaluate the available literature regarding the survival rate and outcomes of dental implants in patients with Papillon-Lefèvre syndrome (PLS). An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all data published from January 1996 till April 2020 using a combination of the following keywords: 'Papillon Lefévre Syndrome', 'prosthodontic rehabilitation' and 'dental implant' according to the PRISMA guidelines for the focused research question constructed using the PICO criteria. Clinical trials and observational studies on implant placement in PLS patients reported in English language were included in the study. A total of 10 studies (nine case reports and one case series) comprising 124 dental implants placed in 13 PLS patients were included. The follow-up period ranged from 4 months to 9 years. With regard to implant loading, 9 studies reported delayed loading, while one study did not provide any information regarding the nature of implant loading. The design of prosthodontic superstructure was either a removable or fixed prosthesis. Out of the 124 inserted implants, 20 (16%) were reported as failed. The overall survival rate was 84%. The limited available evidence suggests that the survival rate of dental implants in patients with PLS is lower than that among healthy individuals. Nevertheless, no strict contraindication for implant-supported prosthesis seems to be justified in this group of patients. Further longitudinal studies with adequate follow-up periods are highly warranted. The prognosis of implant treatment for PLS patients has not yet been established. Dental practitioners should follow a careful approach in planning the dental implant treatment for this cohort of patients.

A novel mutation in the cathepsin C (CTSC) gene in Iranian family with Papillon-Lefevre syndrome.

ObjectivesIn this study, we analyzed the whole exomes of CTSC gene in a family with history of PLS.Materials and methodsGenomic DNA was extracted from peripheral blood and genotype analysis was performed. The mutated protein sequence was used to find the best possible tertiary structure for homology modeling. The homology modeling of the novel mutation was then performed using the online Swiss‐Prot server. The results were also analyzed for to verify its validity.ResultsThe analysis of CTSC gene elucidated a novel insertion GAC. The novel mutation was proved by analyzing 50 healthy control volunteers. Modeling of the novel found mutation in CTSC gene revealed structural defects that may have caused the functional abnormalities.ConclusionsThe structural analysis of the mutated protein model identifies changes in the stereo‐chemical and the energy level of the mutated protein. Since this protein play a role in the activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, such structural defects may lead to its malfunction causing dysfunctioning of immune defense mechanisms.

Papillon Lefevre syndrome associated with recurrent pyogenic abscess of facial skin followed by scarring: A case report

Papillon-Lefévre syndrome (PLS) is an autosomal recessive disorder that is characterised by severe generalized early-onset periodontitis and palmoplantar hyperkeratosis. Besides these cardinal features some patients rarely exhibits recurrent pyogenic infections of skin, hair follicle infection (frunculosis), multiple abscess of skin, hyperhidrosis. This article represents a rare case of 17 year old young male patient with cardinal features of PLS along with history of recurrent pyogenic abscess of facial skin followed by scarring since childhood. There are multiple etiological factors like genetic, immunological, and microbial factors, consanguineous marriage and reduced host defense mechanism. Patients with PLS have increased susceptibility to infections. Over 300 cases have been reported till now in dental and medical literature with most of the cases discovered amongst Africans, Arabs and, Indians with 25% patients showing recurrent pyogenic infections. Management of the disorder primarily involves conventional periodontal treatment; oral hygiene instructions, antiseptic mouth rinses; and systemic antibiotic. Skin lesions are usually treated with topical application of emollients, keratolytic agents, steroids, and oral retinoid.

Potential Role of the Mitochondria for the Dermatological Treatment of Papillon-Lefèvre

The Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS.

Novel Compound Heterozygous Mutations in CTSC Gene in a Chinese Family with Papillon-Lefevre Syndrome

Papillon-Lefevre syndrome (PLS) (OMIM: 245000) is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early onset periodontitis, resulting in the premature loss of the deciduous and permanent teeth. PLS is caused by mutations in the cathepsin C (CTSC) gene (OMIM: 602365), which has been mapped to chromosome 11q14–q21. Genetic analysis can help early and rapid diagnosis of PLS. Here we report on a Chinese PLS pedigree with two affected siblings. We have identified two novel compound heterozygous mutations c.763T>C (p.C255R) and c.1015C>A (p.R339S) in the CTSC gene. The two mutations expand the spectrum of CTSC mutations in PLS.

Nonsurgical periodontal management of Papillon–Lefevre syndrome

Papillon–Lefevre syndrome (PLS) is an autosomal recessive genetic disorder caused by a deficiency in Cathepsin C. It is characterized by palmoplantar keratosis and premature loss of both primary and permanent dentition. Patients are often edentulous at an early age. Other symptoms include increased susceptibility to infections. Various etiologic factors such as genetic mutations, immunologic alterations, and bacteria have been implicated. We present a case report of 12-year-old female who reported to the dental clinic with a history of pain and swollen gums. Family history revealed consanguinity. On clinical examination, there was palmoplantar keratosis and examination of the oral cavity showed generalized periodontal pockets, tooth mobility, and periodontal abscess. Radiographic examination revealed generalized horizontal bone loss. Lateral cephalogram revealed retarded somatic development. A diagnosis of PLS was arrived based on history, clinical and radiological findings. Nonsurgical periodontal treatment along with the treatment of skin lesions was performed. A combined and intensive mechanical and antimicrobial treatment with supportive periodontal treatment in PLS patients may halt the periodontal disease progression. The dentists should be aware of the same because an early diagnosis of the syndrome can help to preserve the teeth by the timely institution of treatment, using a multidisciplinary approach.

Response of papillon–Lefevre syndrome to acitretin

Papillon–Lefevre (PLS) is a rare autosomal recessive disorder of keratinization characterized by symmetric, trans-gradient type palmoplantar keratoderma (PPK), rapidly progressive periodontopathy, and precocious loss of dentition. The management of this condition is difficult and needs a combined approach of both dermatologist and periodontologist. Different treatment options tried previously include keratolytic agents such as salicylic acid, urea, topical steroids in combination with keratolytic, propylene glycol, and systemic retinoids such as etretinate, isotretinoin, and acitretin. Both skin and dental manifestations show good therapeutic responses to systemic retinoids. Thereby, we report a case of PLS in a young female child who showed an excellent response to oral acitretin therapy.

Papillon Lefevre Syndrome: Diagnosis and Management in Two Affected Siblings – A Case Report

Papillon-Lefèvre syndrome (PLS) an autosomal recessive disorder characterized by diffuse transgradient palmar-plantar hyperkeratosis, with premature loss of deciduous and permanent teeth, along with the calcification of the dura mater. This results in teeth radiographically appearing as “floating” in the soft tissue. Genetic studies of patients with PLS have mapped the major gene locus to chromosome 11q24-q21 and revealed mutation and loss of function of the cathepsin gene. It affects 1- 4 people per 1 million population with no gender or racial predilection. Dermatological manifestations, usually occurs before four years of age, include hyperkeratosis of palms and soles, nail dystrophy, hyperhidrosis and keratinization on elbows and knees with the lesions appearing as white, yellow-like or red plaques or patches that then develop cracks, crusts, or deep fissures. KEYWORD: Papillon-lefevre syndrome, hyperkeratosis HOW TO CITE: Zalan AK, Zubairy KK, Maxood A, Niazi M, Zaman H, Gul A, Anser M. Papillon lefevre syndrome: Diagnosis and management in two affected siblings – A case report. J Pak Dent Assoc 2020;29(4):264-268.

Dental prosthetic rehabilitation of Papillon-Lefèvre syndrome: a case report.

Papillon-Lefèvre syndrome (PLS) is a rare disorder characterized by palmar plantar hyperkeratosis and rapidly progressive periodontitis with loss of deciduous and permanent dentition at an early age. It is reported to occur in 1 to 4 individuals per million people. This case report presents highlighting features of the rare PLS in a 17-year old male who complained of discomfort while mastication and it was accompanied with symmetrical, sharply demarcated erythematous plaques involving the skin of the palms and soles, which extended to the finger joints, elbows, and knees. Along with the rough and dry skin, hyperhidrosis of lesion with a foul odor and transverse grooving of nails were noted. The past dental history revealed normal eruption of deciduous teeth followed by pre-mature mobility and shedding in 4-6 months. Permanent teeth also showed normal eruption and early shedding in the next 4-5 years. Complete edentulous maxillary and mandibular arches led to a decrease in alveolar bone and facial heights. There was no similar disorder in the patient’s family but family history revealed the consanguineous marriage of the patient’s parents.

CLINICAL AND MOLECULAR ANALYSIS IN PAPILLON-LEFÈVRE SYNDROME

Papillon-Lefevre syndrome (PLS) is a cathepsin C (CTSC)-associated disorder characterized by palmar and plantar hyperkeratosis and aggressively progressing periodontitis. Here we report the clinical and genetic features of 5 PLS patients presenting with a severe periodontal breakdown in primary and permanent dentition, hyperkeratosis over the palms and soles, and recurrent sinusitis and/or tonsillitis. Mutation analysis revealed 2 novel homozygous recessive mutations (c.947 T>C and c.1010 G>C) and 1 previously described homozygous recessive mutation (c.901 G>A), with the parents heterozygous carriers, in 3 families (4 patients). The fourth family presented with the CTSC c.628 C>T heterozygous mutation, which was inherited maternally. The patient carrying the CTSC c.628 C>T mutation featured the classical PLS phenotype, but no PLS clinical characteristics were found in his carrier mother. These findings indicate that both homozygous and heterozygous mutations in the cathepsin C heavy chain domain may lead to the classical PLS phenotype, suggesting roles for epistasis or gene-environment interactions on determination of PLS phenotypes.

Oral rehabilitation of Papillon-Lefèvre syndrome patients by dental implants: a systematic review.

ObjectivesPapillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder. These patients lose their teeth at a young age and are in need of prosthetic rehabilitation. The aim of this systematic review was to assess the success of dental implant placement in these patients.Materials and MethodsAn electronic search was performed in PubMed Central, Scopus, and Web of Science using the keyword “Papillon–Lefèvre syndrome” AND “dental implant” OR “prosthodontics”. Articles reporting implant placement in patients with PLS until July 2019 were included.ResultsAssessment of the included 11 articles reporting 15 cases showed 136 implant placements in these patients. Implant failure occurred in 3 patients (20 implants). The peri-implantitis and failure rate was higher in the maxilla. Meta-analysis showed the probability of failure to be 7% (95% confidence interval [CI] 0%-31%) for maxillary implants and 2% (95% CI 0%-9%) for mandibular implants. The follow-up time ranged between 1 and 20 years. Healing after bone graft and implant placement in these patients was uneventful.ConclusionDental implants may be a viable treatment option for PLS patients. Implantation can help preserve alveolar bone if the patients’ immunological and growing conditions are well-considered and proper oral hygiene and compliance with the maintenance program are continued.

Use of Removable Partial Denture in Child with Papillon-Lefevre Syndrome: Case Report

Background: Papillon-Levefre Syndrome (PLS) is a rare genetic disorder with prevalence of 1-4 cases per millions of birth, characterized by the presence of palmar-plantar hyperkeratosis and rapid periodontal destruction of both the primary and secondary dentition. Purpose: This clinical report described such a rare condition with special attention on its diagnostic characterization, various treatment options and Prosthodontic rehabilitation. Case: Five years-old boy accompanied by his mother came to Pediatric Dentistry Specialist Clinic, Universitas Airlangga Dental Hospital - Surabaya with the chief complaint of gradually loss of upper and lower teeth since the patient was 3 years old. Case Management: Removable partial denture was chosen because it was considered as an appliance that can recover the function of mastication, speech and aesthetic patient. Removable partial denture was designed to replace 51, 52, 53, 54, 55, 61, 62, 63, 64, 65, 72, 73, 74, 75, 82, 83, 84 and 85 with retention on 16, 26, 36 and 46, and anterior bite riser on 31 and 41. Conclusion.Removable partial denture is the treatment of choice for children with PLS who are still in the growth period because it can recover mastication and aesthetic functions, have a good aesthetic, and easy maintenance that could done by the child.

Papillon-Lefèvre Syndrome: Detrimental Periodontal Condition in the Affected Individuals

This paper aims to highlight the detrimental periodontal condition in patients with Papillon-Lefèvre syndrome (PLS) and the pivotal role of a Periodontist in the diagnosis of the condition. PLS is also known as palmo-plantar keratosis (PPK) with an unusual periodontal status. Uncontrolled early-onset periodontitis, which affects both primary and permanent dentitions alike, is a hallmark of the syndrome. PLS patients’ exhibit defected neutrophil chemotactic function due to substandard activity of Cathepsin C (CTSC) gene. The result is the failure of elimination of periodontal pathogens that leads to severe periodontal destruction. We reported a case of an 11 years old Pakistani girl affected with PLS whose parents are consanguineously married. Since PLS is a rare autosomal recessive disorder and multiple consanguinity in a family, increases the risk of the occurrence of the syndrome in the off springs, the case report also highlights the importance of pre-marital genetic mapping and conception counseling for the families.

Papillon-Lefèvre syndrome: Oral aspects and treatment.

Papillon-Lefèvre syndrome (PLS) is a rare disorder characterized by diffuse palmoplantar erythematous, fissured hyperkeratosis, and aggressive periodontal disease that starts in the early periods of childhood. Periodontal disease occurs with the early loss of deciduous teeth at the age of 2 to 4 years, followed by the loss of permanent teeth during adolescence. Prosthodontics management of PLS patients is very complex and sometimes requires invasive therapeutic treatments. Early diagnosis is essential for correct treatment management avoiding the possibility that patients are early edentulous. Management could be a conventional periodontal treatment and pharmacological therapy but in severe cases, digital techniques, could be help the clinician for increased patient comfort and minimized tissue damage.

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

掌跖角化-牙周破坏综合征合并先天性眼病一例

掌跖角化-牙周破坏综合征合并先天性眼病一例

Palmoplantar keratoderma, oral involvement, and homozygous CTSC mutation in two brothers from Cambodia

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.

Gene Editing ELANE in Human Hematopoietic Stem and Progenitor Cells Reveals Disease Mechanisms and Therapeutic Strategies for Severe Congenital Neutropenia

Newburger: TransCytos LLC: Consultancy; X4 Pharmaceuticals: Consultancy, Honoraria.

A Case Report: Papillon Lefevre Syndrome

Study Background: Papillon Lefevre Syndrome (PLS) is an autosomal recessive inherited genetic disorder characterized by palmoplantar hyperkeratosis and premature loss of deciduous and permanent teeth. Mutation of cathepsin C gene has been detected in the patient with PLS. In this case report, oral and radioghaphic findings of one PLS patient were discussed. 14 year old male patient diagnosed with PLS after radiographic, dermatologic and dental examination was referred to our clinic due to severe gingival inflamation and mobility. Severe gingival inflamation, alveolar bone resorption and multiple teeth loss due to periodontal reasons were observed. Mild palmar and moderate plantar hyperkeratosis were observed but no other systemic problems were detected. Methods: Non-surgical periodontal treatment was perfomed among multiple sessions and in each session subgingival tissues had been irrigated with %2 chlorhexidine irrigation solution. To reduce severe gingival inflammation antibiotherary has been prescribed. Hopeless teeth were extracted. Results: After non-surgical periodontal treatment and antibiotherary severe gingival inflammation was reduced but not eliminated completely, mobility score of some teeth reached to zero score, patient was motivated about oral hygiene and was taken into maintanence phases. After having extracted hopeless teeth patient was directed for prosthodontic rehabilitation. Conclusion: PLS is a rare autosomal recessive disorder. With PLS-specific dermatologic findings and characteristic periodontal view, it is possible to be able to identify the disease in its very early stages. Early diagnosis of the disease and institution of an appropriate periodontal and antimicrobial treatment might improve the prognosis.