Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

The use of localised CBCT to image inflammatory collateral cysts: a retrospective case series demonstrating clinical and radiographic features.

INTRODUCTION: Inflammatory collateral cysts are uncommon cysts primarily affecting first permanent molars during their eruption. There are diagnostic challenges that can be overcome with CBCT imaging. However, given the paediatric age group for this condition, there are patient cooperation and radiation dose factors to consider when justifying the scan. The aim of this case series study is to illustrate the value of CBCT in imaging and diagnosing inflammatory collateral cysts in paediatric patients, to highlight the need for a multidisciplinary approach for this uncommon pathological condition and to review the relevant literature. CASE SERIES DESCRIPTION AND RESULTS: We present three patients aged between 6 and 11 years of age with inflammatory collateral cysts affecting their first or second permanent molars for which CBCT imaging was utilised. All patients underwent cyst enucleation with preservation or extraction of affected teeth under general anaesthesia. DISCUSSION: Inflammatory collateral cysts are likely to be under reported given their indistinct clinical features and radiological signs. Conventional planar radiographs may not reveal this lesions size and full extent. CBCT overcomes these limitations; however, careful assessment of patient cooperation is needed and a low-dose protocol should be used. CONCLUSIONS: CBCT can provide useful imaging information which is difficult to obtain using conventional radiography, especially in cases where an inflammatory collateral cyst is suspected.

Oral lichenoid lesions after hepatitis B vaccination.

The association of mucocutaneous lichen planus and chronic liver disease is widely recognized. The hepatitis B and C viruses have been implicated as being important in this association, although their exact role remains unclear. Recently, lichenoid lesions of the skin after a hepatitis B vaccination have also been reported. In this case, a woman of Southeast Asian origin had lichenoid lesions affecting the oral mucous membranes develop after she was vaccinated against hepatitis B. The lesions appeared 3 weeks after the administration of the third dose of the vaccine and persisted for about 1 year. As the use of the hepatitis B vaccine becomes more widespread, more such cases can be expected to be encountered.

A double-blind cross-over trial of a mucin-containing artificial saliva.

A double-blind, five phase, cross-over clinical trial was used to compare a mucin-based artificial saliva (Saliva Orthana) with its non-mucin base and water. Thirty patients, acting as their own controls, took part. Saliva Orthana offered significantly greater relief from xerostomia compared with its base or water, and was significantly better at relieving soreness than water. In terms of overall preference, it was ranked significantly higher than either alternative.

Opinions and attitudes of the UK's GDPs and specialists in oral surgery, oral medicine and surgical dentistry on oral cancer screening.

OBJECTIVE: To survey two broad areas of oral cancer awareness and management of patients at risk of oral cancer by specialists in oral surgery, oral medicine, surgical dentistry and general dental practitioners (GDPs) in the UK. The first of these included knowledge and awareness of aetiological factors, changing patterns of disease, and screening/detection programmes including their effectiveness. The second included oral cancer detection methods, advice on avoidance of high-risk activity and self-examination, and referral pattern of GDPs. DESIGN AND METHOD: A pretested, 44-item questionnaire, a covering letter, a brief outline of the research protocol and return, stamped envelope were mailed in March 2003. A sample of 200 GDPs whose names were obtained from the General Dental Council's main list and 305 dental specialist names obtained from specialist's list in surgical dentistry, oral medicine and oral surgery were selected randomly. Information on oral cancer awareness and practice, screening practice and education was obtained. RESULTS: The response rate was 66.9%. The knowledge of the dental specialists was consistent with that in reports of current aetiological studies on oral cancer. However there were gaps in the GDP's knowledge and ascertainment of oral cancer risk factors. Over 70% of the dental specialists provided counselling advice on the risks of tobacco and alcohol habits compared with 41.2% of GDPs. More GDPs (52.4%) than specialists (35.4%) believed that oral cancer screening on a national basis would be effective in decreasing the mortality of oral cancer. Over 95% of all respondents used a visual examination for oral cancer screening and 89.9% of all respondents strongly believed that visual screening is effective in the early detection of oral cancer. CONCLUSION: The results showed that GDPs had knowledge gaps in their awareness of oral cancer risk factors and the application of preventive measures. Most dental health providers in the UK perform visual screening of the oral mucosa for their patients. Opinion was equivocal as to whether a nationally based screening programme similar to cervical cancer would be effective in improving the mortality and morbidity of oral cancer.

Complications of the naevoid basal cell carcinoma syndrome: results of a population based study.

There are many potential complications which have been reported in association with the naevoid basal cell carcinoma syndrome. We have been able to show the relative frequencies of these problems in a population based study of 84 cases in the north west of England. The major complications of basal cell carcinomas and jaw cysts occur in over 90% of patients by 40 years of age, but may both occur before 10 years of age. Less well described complications are ovarian calcification or fibroma (24%), medulloblastoma (5%), cardiac fibroma (3%), cleft palate (5%), and ophthalmic abnormalities such as squint or cataract (26%). This study more clearly defines the possible complications of the syndrome and gives clearer guidelines for counselling and screening affected and at risk persons.

Dento-osseous changes as diagnostic markers in familial adenomatous polyposis families.

BACKGROUND: We have previously described a weighted index for determining the diagnostic significance of dento-osseous changes observed on dental panoramic radiographs (DPRs) in individuals at 50% risk of inheriting Familial Adenomatous Polyposis (FAP). A diagnostic test based on this index (Dental Panoramic Radiograph Score, DPRS) was shown to have a sensitivity of 69% and specificity of 100%. OBJECTIVES: To evaluate the validity of the diagnostic test in an independent sample of individuals at 50% risk of inheriting FAP. DESIGN: A retrospective assessment of DPRs in individuals at 50% risk of inheriting FAP. SUBJECTS AND METHODS: A final year dental student assessed blindly and independently, DPRs from an independent sample (n = 119) of affected (n = 26), unaffected (n = 78) and clinically low risk individuals (n = 15). This revealed a sensitivity and specificity of 62 and 97% respectively which is in close agreement with results of the previous study. The dental student's training in assessing DPRs was previously tested using radiographs from 81 individuals from our original study. Weighted Kappa statistics were used to test for agreement. A kappa score of 0.82 (95% confidence interval 0.70-0.93) indicated almost perfect agreement. MAIN OUTCOME: The DPRS is a reproducible and valid index for assessing the diagnostic significance of dentoosseous changes, in individuals at 50% risk of FAP, even in relatively inexperienced hands.

The dental phenotype in familial adenomatous polyposis: diagnostic application of a weighted scoring system for changes on dental panoramic radiographs.

A weighted scoring system (Dental Panoramic Radiograph Score) taking into consideration the nature, extent, and site of osseous and dental changes on dental panoramic radiographs in familial adenomatous polyposis is described. The weighting takes into consideration the incidence of the anomaly in the general population. The reliability of the system was tested by application to 85 people known to be affected by clinical or mutation analysis, 30 people lacking mutation in the adenomatous polyposis gene, and 19 people shown to be at low risk (< 1%) by linkage analysis. Using the highest thresholds, a specificity of 100% and sensitivity of approximately 68% was obtained. If all positive findings were considered as significant, sensitivity was increased to approximately 82% but the specificity was reduced to approximately 88%. Significant DPRS findings were observed at a significantly higher frequency in patients aged over 20 compared to the patients aged 20 and under. Overall, approximately 68% of the affected subjects had significant changes, and approximately 18% had normal appearance on DPR, with the remainder having changes classified as minimal or equivocal.

Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis.

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.

British Society for Oral and Maxillofacial Pathology, UK: minimum curriculum in oral pathology.

This paper describes a minimum curriculum in oral pathology for undergraduate dental education in the United Kingdom prepared by the Teachers Group of The British Society of Oral and Maxillofacial Pathology. Curricular development in UK dental schools is overseen by the General Dental Council (GDC), the Quality Assurance Agency for Higher Education (QAA) and the European Union. These organisations define the framework for education and learning outcomes but provide little or no detailed guidance on syllabus or curriculum. This recommended minimum curriculum has been drawn up by a consensus process involving teachers of oral pathology from all 13 UK and one Irish dental schools and is cross-referenced to the GDC and QAA published requirements for undergraduate dental education.

Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene.

Familial adenomatous polyposis (FAP) is associated with a number of extraintestinal manifestations, which include osteomas, epidermoid cysts, and desmoid tumors, often referred to as "Gardner syndrome." Recent studies have suggested that some of the phenotypic features of FAP are dependent on the position of the mutation within the APC gene. In particular, the correlation between congenital hypertrophy of the retinal pigment epithelium (CHRPE) and APC genotype indicates that affected families may be divided into distinct groups. We have investigated the association between the dentoosseous features of GS on dental panoramic radiographs (DPRs) and APC genotype in a regional cohort of FAP families. DPRs were performed on 84 affected individuals from 36 families, and the dento-osseous features of FAP were quantified by a weighted scoring system. Significant DPR abnormalities were present in 69% of affected individuals. The APC gene mutation was identified in 27 of these families, and for statistical analysis these were subdivided into three groups. Group 1 comprised 18 affected individuals from seven families with mutations 5' of exon 9; these families (except one) did not express CHRPE. Groups 2 comprised 38 individuals from 16 families with mutations between exon 9 and codon 1444, all of whom expressed CHRPE. Group 3 comprised 11 individuals from four families with mutations 3' of codon 1444, none of whom expressed CHRPE. Families with mutations 3' of codon 1444 had significantly more lesions on DPRs (P < .001) and appeared to have a higher incidence of desmoid tumors. These results suggest that the severity of some of the features of Gardner syndrome may correlate with genotype in FAP.

Florid oral manifestations in an atypical familial adenomatous polyposis family with late presentation of colorectal polyps.

Early identification and prophylactic surgery are essential in preventing development of malignancy in colorectal polyps in familial adenomatous polyposis (FAP). Previous studies indicate a 100% cumulative risk of developing colonic polyps in individuals with FAP by the age of 34 yr. However, we have previously reported late-onset and non-penetrance of polyposis in four families. We describe here in detail one of these families with florid oral manifestations detectable on panoramic radiography of the jaws, which were instrumental in the diagnosis of FAP in the index patient and for ascertainment of her family for screening. The pathological adenomatous polyposis coli (APC) gene mutation in this family was shown to segregate with dento-osseous changes. Panoramic jaw radiography is a common examination carried out prior to dental or oral surgical procedures. This case illustrates the importance of appropriate investigations, including family history and colonoscopy, even in relatively older patients with radiological findings such as those described here and in members of their families at risk of FAP.