RESUMEN
OBJECTIVES: Agnathia-otocephaly complex is a rare condition characterized by mandibular hypoplasia or agnathia, ear anomalies (melotia/synotia) and microstomia with aglossia. This severe anomaly of the first branchial arch is most often lethal. The estimated incidence is less than 1 in 70.000 births, with etiologies linked to both genetic and teratogenic factors. Most of the cases are sporadic. To date, two genes have been described in humans to be involved in this condition: OTX2 and PRRX1. Nevertheless, the overall proportion of mutated cases is unknown and a significant number of patients remain without molecular diagnosis. Thus, the involvement of other genes than OTX2 and PRRX1 in the agnathia-otocephaly complex is not unlikely. Heterozygous mutations in Cnbp in mice are responsible for mandibular and eye defects mimicking the agnathia-otocephaly complex in humans and appear as a good candidate. Therefore, in this study, we aimed (i) to collect patients presenting with agnathia-otocephaly complex for screening CNBP, in parallel with OTX2 and PRRX1, to check its possible implication in the human phenotype and (ii) to compare our results with the literature data to estimate the proportion of mutated cases after genetic testing. MATERIALS AND METHODS: In this work, we describe 10 patients suffering from the agnathia-otocephaly complex. All of them benefited from array-CGH and Sanger sequencing of OTX2, PRRX1 and CNBP. A complete review of the literature was made using the Pubmed database to collect all the patients described with a phenotype of agnathia-otocephaly complex during the 20 last years (1998-2019) in order (i) to study etiology (genetic causes, iatrogenic causes ) and (ii), when genetic testing was performed, to study which genes were tested and by which type of technologies. RESULTS: In our 10 patients' cohort, no point mutation in the three tested genes was detected by Sanger sequencing, while array-CGH has allowed identifying a 107-kb deletion encompassing OTX2 responsible for the agnathia-otocephaly complex phenotype in 1 of them. In 4 of the 70 cases described in the literature, a toxic cause was identified and 22 out the 66 remaining cases benefited from genetic testing. Among those 22 patients, 6 were carrying mutation or deletion in the OTX2 gene and 4 in the PRRX1 gene. Thus, when compiling results from our cohort and the literature, a total of 32 patients benefited from genetic testing, with only 34% (11/32) of patients having a mutation in one of the two known genes, OTX2 or PRRX1. CONCLUSIONS: From our work and the literature review, only mutations in OTX2 and PRRX1 have been found to date in patients, explaining around one third of the etiologies after genetic testing. Thus, agnathia-otocephaly complex remains unexplained in the majority of the patients, which indicates that other factors might be involved. Although involved in first branchial arch defects, no mutation in the CNBP gene was found in this study. This suggests that mutations in CNBP might not be involved in such phenotype in humans or that, unlike in mice, a compensatory effect might exist in humans. Nevertheless, given that agnathia-otocephaly complex is a rare phenotype, more patients have to be screened for CNBP mutations before we definitively conclude about its potential implication. Therefore, this work presents the current state of knowledge on agnathia-otocephaly complex and underlines the need to expand further the understanding of the genetic bases of this disorder, which remains largely unknown. CLINICAL RELEVANCE: We made here an update and focus on the clinical and genetic aspects of agnathia-otocephaly complex as well as a more general review of craniofacial development.
Asunto(s)
Anomalías Craneofaciales , Anomalías Maxilomandibulares , Animales , Anomalías Craneofaciales/genética , Humanos , Anomalías Maxilomandibulares/genética , Ratones , Mutación , FenotipoRESUMEN
Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.
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Hibridación Genómica Comparativa/métodos , Asesoramiento Genético/ética , Asesoramiento Genético/métodos , Hallazgos Incidentales , Revelación/ética , Femenino , Francia , Genes Dominantes/genética , Genes Recesivos/genética , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Masculino , Análisis por Micromatrices/métodos , Relaciones Médico-Paciente/ética , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The aim of this report is (1) to provide a global overview of oral health conditions in older people, use of oral health services, and self care practices; (2) to explore what types of oral health services are available to older people, and (3) to identify some major barriers to and opportunities for the establishment of oral health services and health promotion programmes. METHODS: A postal questionnaire designed by the World Health Organization (WHO) was distributed worldwide to the Chief Dental Officers or country oral health focal points at ministries of health. WHO received 46 questionnaires from countries (39% response rate). In addition, systematic data were collected from the WHO Global Oral Health Data Bank and the World Health Survey in order to include oral health information on the remaining countries. In total, the data base covers 136 out 193 countries, i.e., 71% of all WHO Member States. RESULTS: Dental caries and periodontal disease comprise a considerable public health problem in the majority of countries. Significant disparities within and between regions are observed in epidemiologic indicators of oral disease. The prevalence rates of tooth loss and experience of oral problems vary substantially by WHO Region and national income. Experience of oral problems among older people is high in low income countries; meanwhile, access to health care is poor, in particular in rural areas. Although tooth brushing is the most popular oral hygiene practice across the world, regular tooth brushing appears less common among older people than the population at large. In particular, this practice is less frequent in low income countries; in contrast, traditional oral self-care is prevalent in several countries of Africa and Asia. While fluoridated toothpaste is widely used in developed countries, it is extremely infrequent in most developing countries. Oral health services are available in developed countries; however, the use of such services is low among the older people. Lack of financial support from government and/or lack of third party payment systems render oral health services unaffordable to them. According to the country reports, health promotion programmes targeting older people are rare and this reflects the lack of oral health policies. Although some countries have introduced oral health promotion initiatives, worldwide there are few population-oriented preventive or curative activities currently implemented that focus specifically on the elderly. Barriers to the organization of such programmes relate to weak national health policy, lack of economic resources, the impact of poor oral health, and lack of tradition in oral health. Opportunities for oral health programmes for old-age people are related to updated information on the burden of oral disease and need for care, fair financing of age-friendly primary health care, integration of oral health into national health programmes, availability of oral health services, and ancillary personnel. CONCLUSION: It is highly recommended that countries establish oral health programmes to meet the needs of the elderly. Relevant and measurable goals must be defined to direct the selection of suitable interventions to improve their oral health. The common risk factors approach must be applied in public health interventions for disease prevention. The integration of oral health into national general health programmes may be effective to improve the oral health status and quality of life of this population group.
Asunto(s)
Salud Global , Política de Salud , Salud Bucal , Salud Pública , Anciano , Cariostáticos/uso terapéutico , Auxiliares Dentales/provisión & distribución , Cuidado Dental para Ancianos/economía , Cuidado Dental para Ancianos/estadística & datos numéricos , Caries Dental/epidemiología , Fluoruros/uso terapéutico , Costos de la Atención en Salud/estadística & datos numéricos , Promoción de la Salud/estadística & datos numéricos , Recursos en Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Estado de Salud , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Renta , Higiene Bucal/estadística & datos numéricos , Enfermedades Periodontales/epidemiología , Odontología Preventiva/estadística & datos numéricos , Atención Primaria de Salud/economía , Calidad de Vida , Servicios de Salud Rural/estadística & datos numéricos , Pérdida de Diente/epidemiología , Cepillado Dental/estadística & datos numéricos , Pastas de Dientes/uso terapéutico , Organización Mundial de la SaludRESUMEN
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model provides a valuable paradigm of the energy deficiency disorders found in childhood. In such disorders, anticonvulsants may provide neuroprotection by modulating cellular energy consumption and by exerting favorable pleiotropic effects on neuronal survival. To verify such hypothesis, we tested the effects of levetiracetam, vigabatrin, gabapentine, pregabaline, tiagabine, clonazepam and lamotrigine on neuroprotection in the MPTP mouse model. The membrane dopamine transporter (DAT) density, which provides a reliable index of dopaminergic neurons survival in the basal ganglia, was assessed by semi-quantitative autoradiography of the striatum. Unlike all other anticonvulsants tested, lamotrigine provided a significant and dose-dependent neuroprotection in these experimental conditions. Lamotrigine, a widely used and well-tolerated molecule in children, could provide neuroprotection in various energy deficiency disorders.
Asunto(s)
Anticonvulsivantes/farmacología , Enfermedades de los Ganglios Basales/metabolismo , Enfermedades de los Ganglios Basales/prevención & control , Ganglios Basales/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Intoxicación por MPTP/metabolismo , Intoxicación por MPTP/prevención & control , Fármacos Neuroprotectores , Animales , Autorradiografía , Enfermedades de los Ganglios Basales/patología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Relación Dosis-Respuesta a Droga , Lamotrigina , Intoxicación por MPTP/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Neostriado/patología , Triazinas/farmacologíaRESUMEN
The life-course framework stresses the importance of social, psychosocial, and biological factors in early life on the development of later disease. From this perspective, the association between edentulousness of mothers and their children's caries risk has not been studied. Therefore, a sample of 6303 mother-child pairs was randomly selected in Quebec (Canada). Mothers (6039 dentate and 264 edentulous) completed a self-administered questionnaire, and their children, aged 5 to 9 years, were clinically examined. Bivariate analyses and multiple logistic regressions showed that edentulous mothers' children are more likely to experience caries on both primary [OR=1.7 (1.3-2.3)] and permanent [OR=1.4 (1.0-2.0)] dentitions when compared with dentate mothers' children. These results are independent of socio-economic status, age, gender, and children's oral-health-related behaviors. Our study is the first to show that edentulous mothers' children constitute a group at risk of caries. It also highlights the need for a better understanding of the mother-child transmission of risk.
Asunto(s)
Actitud Frente a la Salud , Índice CPO , Caries Dental/epidemiología , Arcada Edéntula/epidemiología , Relaciones Madre-Hijo , Adulto , Canadá/epidemiología , Niño , Preescolar , Atención Odontológica/estadística & datos numéricos , Caries Dental/complicaciones , Encuestas de Salud Bucal , Dentición Permanente , Femenino , Humanos , Arcada Edéntula/complicaciones , Persona de Mediana Edad , Salud Bucal , Factores de Riesgo , Estadísticas no Paramétricas , Diente PrimarioRESUMEN
Non organic dysphonia or functional voice disorders are the consequence of a vocal misuse or overuse with inefficient oral communication. Any stage of voice production can be altered. A review of physiopathological, aerodynamic and biomechanical mechanisms will help to understand the onset of dysphonia. Organic lesions as a consequence of functional voice disorders are frequent but the link is not easy to establish. It is important to look for various physiologic, anatomic, environmental, behavioural and infectious factors that could induce or aggravate non organic dysphonia, as they can benefit from specific treatment. A thorough functional and organic assessment is the first step of the rehabilitation process, taking into account the patient's expectations about his voice handicap.