RESUMO
Introduction: The present report describes the case of a 12-year-old patient with 17-year follow-up who was previously diagnosed with Papillon-Lefèvre Syndrome (PLS), which is a rare autosomal recessive irregularity in the cathepsin C gene (CTSC) characterized by palmoplantar hyperkeratosis and premature loss of primary and permanent teeth. Case Report: A specific mutation in the c.203 T > G gene inducing loss of function leading to PLS was detected, as was a mutation in the HLA-DRB1*11 allele, which is associated with this syndrome. There is no consanguinity of the parents, and the siblings are entirely healthy. Early identification of the main characteristics of this syndrome is imperative. Accurate diagnosis by genetic analysis allows differential diagnoses and timely comprehensive dental treatment. Conclusions: Additionally, it allows consultation with a dermatologist to maintain or improve the quality of life of patients with this condition due to progressive worsening and severity of the main physical manifestations. Keywords: Papillon-Lefevre Disease; Keratoderma, Palmo-plantar; Cathepsin C; Periodontitis; Skin Diseases, Genetic; Case reports
Introducción: El presente reporte describe el caso de un paciente de 12 años de edad con 17 años de seguimiento a quien previamente se le diagnosticó Síndrome de Papillon-Lefèvre (PLS), el cual es una rara irregularidad autosómica recesiva en el gen de la catepsina C (CTSC) caracterizada por hiperqueratosis palmoplantar y pérdida prematura de dientes primarios y permanentes. Reporte de Caso: Se detectó una mutación específica en el gen c.203 T > G que induce pérdida de función que conduce a PLS, así como una mutación en el alelo HLA-DRB1*11, que se asocia a este síndrome. No presenta consanguinidad de los padres, padres y hermanos totalmente sanos. La identificación temprana de las principales características de este síndrome es imperativa. El diagnóstico certero por análisis genético permite diagnósticos diferenciales y tratamientos odontológicos integrales oportunos. Conclusiones: Adicionalmente, permite la consulta con un dermatólogo para mantener o mejorar la calidad de vida de los pacientes con esta condición debido al progresivo empeoramiento y severidad de las principales manifestaciones físicas.
Assuntos
Humanos , Masculino , Criança , Doença de Papillon-Lefevre/diagnóstico por imagem , Ceratodermia Palmar e Plantar , Catepsina C/genética , Doença de Papillon-Lefevre/terapiaRESUMO
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.
Assuntos
Acro-Osteólise/genética , Catepsina C/genética , Ceratodermia Palmar e Plantar/genética , Doença de Papillon-Lefevre/genética , Acro-Osteólise/diagnóstico por imagem , Acro-Osteólise/epidemiologia , Acro-Osteólise/fisiopatologia , Adolescente , Camboja/epidemiologia , Criança , Feminino , Homozigoto , Humanos , Ceratodermia Palmar e Plantar/diagnóstico por imagem , Ceratodermia Palmar e Plantar/epidemiologia , Ceratodermia Palmar e Plantar/fisiopatologia , Masculino , Mutação/genética , Doença de Papillon-Lefevre/diagnóstico por imagem , Doença de Papillon-Lefevre/epidemiologia , Doença de Papillon-Lefevre/fisiopatologia , Linhagem , IrmãosRESUMO
Papillon-Lefèvre syndrome (PLS; MIM#245000) is a rare recessive autosomal disorder characterized by palmar and plantar hyperkeratosis, and aggressively progressing periodontitis leading to premature loss of deciduous and permanent teeth. PLS is caused by loss-of-function mutations in the CTSC gene, which encodes cathepsin C. PLS clinical expressivity is highly variable and no consistent genotype-phenotype correlation has been demonstrated yet. Here we report the clinical and genetic features of five PLS patients presenting a severe periodontal breakdown in primary and permanent dentition, hyperkeratosis over palms and soles, and recurrent sinusitis and/or tonsillitis. Mutation analysis revealed two novel homozygous recessive mutations (c.947T>C and c.1010G>C) and one previous described homozygous recessive mutation (c.901G>A), with parents carrying them in heterozygous, in three families (four patients). The fourth family presented with the CTSC c.628C>T mutation in heterozygous, which was inherited maternally. Patient carrying the CTSC c.628C>T mutation featured classical PLS phenotype, but no PLS clinical characteristics were found in his carrier mother. All mutations were found to affect directly (c.901G>A, c.947T>C, and c.1010G>C) or indirectly (c.628C>T, which induces a premature termination) the heavy chain of the cathepsin C, the region responsible for activation of the lysosomal protease. Together, these findings indicate that both homozygous and heterozygous mutations in the cathepsin C heavy chain domain may lead to classical PLS phenotype, suggesting roles for epistasis or gene-environment interactions on determination of PLS phenotypes.
Assuntos
Doença de Papillon-Lefevre/genética , Doença de Papillon-Lefevre/patologia , Adolescente , Adulto , Catepsina C/química , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Modelos Moleculares , Doença de Papillon-Lefevre/diagnóstico por imagem , Adulto JovemRESUMO
Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder, showing oral and dermatological manifestations in the form of aggressive periodontitis, leading to the premature loss of both primary and permanent teeth at a very young age and palmar-plantar hyperkeratosis. It was first described by two French physicians, Papillon and Lefevre in 1924. Immunologic, genetic, or possible bacterial etiologies have been thought to account for etiopathogenesis of PLS. Severe gingival inflammation and periodontal destruction occurred after the eruption of primary teeth. This condition should warn the physicians and dentists as a one of the important sign for the diagnosis of PLS. There have been over 250 cases reported in literature about PLS, but a few of these were in the same family. This study presents oro-dental characteristics, dental treatments, and follow-up of three siblings (age of sisters are 13, 6, and 4 years) with PLS, which is rarely seen in the same family.
Assuntos
Periodontite Agressiva/complicações , Perda do Osso Alveolar/complicações , Ceratodermia Palmar e Plantar/fisiopatologia , Doença de Papillon-Lefevre/genética , Irmãos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Doença de Papillon-Lefevre/complicações , Doença de Papillon-Lefevre/diagnóstico por imagem , Radiografia , Anormalidades Dentárias/genética , Perda de Dente/complicaçõesRESUMO
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.
Assuntos
Catepsina C/genética , Códon sem Sentido/genética , Doença de Papillon-Lefevre/genética , Deleção de Sequência , Periodontite Agressiva/diagnóstico , Periodontite Agressiva/genética , Povo Asiático , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Doença de Papillon-Lefevre/sangue , Doença de Papillon-Lefevre/diagnóstico por imagem , Doença de Papillon-Lefevre/fisiopatologia , Mutação Puntual , Radiografia Panorâmica , Perda de Dente/diagnóstico por imagemRESUMO
Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder characterized by diffuse palmoplantar keratoderma and precocious aggressively progressing periodontitis, leading to the premature loss of deciduous and permanent teeth. Full mouth rehabilitation with implant supported fixed prosthesis provides numerous advantages over the conventional denture in terms of esthetics, function, longevity of the prosthesis, and patient satisfaction. We report a case of PLS in a 19-year-old female who underwent extraction of all the teeth followed by full mouth rehabilitation with implant supported fixed prostheses. A one-year follow up of the case showed functionally and esthetically stable dental implant with no signs of infection or bone loss.
Assuntos
Implantes Dentários , Doença de Papillon-Lefevre/reabilitação , Adulto , Feminino , Humanos , Doença de Papillon-Lefevre/diagnóstico por imagem , Doença de Papillon-Lefevre/cirurgia , Radiografia Panorâmica , Adulto JovemRESUMO
Papillon-Lefevre syndrome and Haim Munk syndrome are palmoplantar keratodermas associated with premature periodontal destruction. The additional findings of Haim Munk Syndrome include onychogryphosis, arachnodactyly, acral osteolysis and pes planus. Both are associated with mutations in the lysosomal protease cathepsin C. We describe a patient with phenotype for Haim Munk Syndrome and genetic analysis revealed a homozygous point mutation in exon 1 of the gene encoding cathepsin C.
Assuntos
Catepsina C/genética , Doença de Papillon-Lefevre/genética , Mutação Puntual , Adulto , Alelos , Éxons/genética , Humanos , Masculino , Doença de Papillon-Lefevre/diagnóstico por imagem , Doença de Papillon-Lefevre/patologia , RadiografiaAssuntos
Abscesso Hepático Piogênico/diagnóstico por imagem , Doença de Papillon-Lefevre/complicações , Infecções Estafilocócicas/diagnóstico por imagem , Adulto , Feminino , Humanos , Abscesso Hepático Piogênico/etiologia , Doença de Papillon-Lefevre/diagnóstico por imagem , Radiografia , Infecções Estafilocócicas/etiologia , UltrassonografiaRESUMO
Of the many palmoplantar keratoderma (PPK) conditions, only Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS) are associated with premature periodontal destruction. Although both PLS and HMS share the cardinal features of PPK and severe periodontitis, a number of additional findings are reported in HMS including arachnodactyly, acro-osteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers. While PLS cases have been identified throughout the world, HMS has only been described among descendants of a religious isolate originally from Cochin, India. Parental consanguinity is a characteristic of many cases of both conditions. Although autosomal recessive transmission of PLS is evident, a more "complex" autosomal recessive pattern of inheritance with phenotypic influences from a closely linked modifying locus has been hypothesised for HMS. Recently, mutations of the cathepsin C gene have been identified as the underlying genetic defect in PLS. To determine if a cathepsin C mutation is also responsible for HMS, we sequenced the gene in affected and unaffected subjects from the Cochin isolate in which both the PLS and HMS phenotypes appear. Here we report identification of a mutation of cathepsin C (exon 6, 2127A--> G) that changes a highly conserved amino acid in the cathepsin C peptide. This mutation segregates with HMS in four nuclear families. Additionally, the existence of a shared common haplotype for genetic loci flanking the cathepsin C gene suggests that affected subjects descended from the Cochin isolate are homozygous for a mutation inherited "identical by descent" from a common ancestor. This finding supports simple autosomal recessive inheritance for HMS in these families. We also report a mutation of the same exon 6 CTSC codon (2126C-->T) in a Turkish family with classical PLS. These findings provide evidence that PLS and HMS are allelic variants of cathepsin C gene mutations.
Assuntos
Catepsina C/genética , Hiperceratose Epidermolítica/genética , Doença de Papillon-Lefevre/genética , Periodontite/genética , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Doença de Papillon-Lefevre/diagnóstico por imagem , Linhagem , Radiografia , Mapeamento por Restrição , Homologia de Sequência de Aminoácidos , SíndromeRESUMO
Periodontitis resulting from Papillon-Lefèvre Syndrome has been known to cause early loss of primary dentition with subsequent involvement of the permanent dentition. In this study, two Papillon-Lefèvre Syndrome patients were followed for 3 years after initial treatment and improvement of their periodontal condition. In addition, two new cases of Papillon-Lefèvre Syndrome are presented. The follow-up treatment of the first two patients included monitoring the oral hygiene and performing ultrasonic scaling. Their present clinical appearance is very satisfactory. The periodontal condition of the third (new) patient was brought under control by extracting the involved deciduous teeth under antibiotic coverage, and by scaling and root planing the already erupted permanent teeth as well as by maintaining a high standard of oral hygiene. In the fourth case, all permanent teeth had erupted and the periodontium had already been severely destroyed. Actinobacillus actinomycetemcomitans was not detected by microbiologic examination after the periodontal conditions improved, except in the fourth case. Western blot analysis showed that the three first three patients had positive antibody response to the same antigens of Actinobacillus actinomycetemcomitans. Phagocytosis by polymorphonuclear neutrophil leukocytes) had not decreased, but the expression of surface receptors of polymorphonuclear neutrophil leukocytes was within the normal limits.
Assuntos
Doença de Papillon-Lefevre/terapia , Aggregatibacter actinomycetemcomitans/imunologia , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Anticorpos Antibacterianos/análise , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Neutrófilos/imunologia , Doença de Papillon-Lefevre/diagnóstico por imagem , Doença de Papillon-Lefevre/microbiologia , Periodontite/diagnóstico por imagem , Periodontite/microbiologia , Periodontite/terapia , Fagocitose , RadiografiaRESUMO
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.