The Effect of mandible advancement splints in mild, moderate, and severe obstructive sleep apnea-the need for sleep registrations during follow up

Objective and design: Our aim was to evaluate the effect of mandible advancement splint (MAS) in mild, moderate, and severe obstructive sleep apnea (OSA). We also determined, if and in which OSA-groups the adequate forward movement in MAS could be quantified without sleep registration for different OSA levels. A retrospective study. Settings: The effect of MAS was measured with clinical methods and by sleep registration. Participants: The series consisted of 103 patients, 75 males and 28 females (mean age 52 years) suffering from mild (32 per cent), moderate (32 per cent), or severe (36 per cent) OSA, who were treated with MAS at Helsinki University Hospital, Finland during the years 2011-2012. Seventy per cent of the patients had tried continuous positive airway pressure (CPAP) before MAS. Results: The lower the body mass index (BMI) was the bigger the probability was to get apnea/hypopnea index (AHI) values <5 per hour with MAS (P <0.01). The total AHI decreased significantly from the baseline with MA (P <0.001). The mean oxygen desaturation index (ODI4%) improved significantly from 16 per hour (range 1-76) to 5.3 per hour (range 0.2-49), (P <0.01), and the minimum oxygen saturation improved significantly from 84 per cent (67-91) to 87 per cent (68-93), (P <0.01). The reduction of AHI with MAS was significantly bigger in patients with a previous CPAP experience (73 per cent) than those who did not tried CPAP therapy. The positive correlation was found between the decrease in AHI and the increase of the protrusion in MAS. Conclusion: Both sleep recordings and subjective indicators demonstrated that MAS therapy was successful in OSA based on ESS, total AHI, ODI4%, and minimum oxygen saturation values. It seems useful to increase the protrusion at its maximal clinical tolerance. An experienced dentist could make therapeutically decision concerning the follow up of MAS efficacy regardless of the result of sleep study. We suggest that MAS is a valuable treatment alternative for CPAP. However, the previous use of CPAP with MAS as well as lower baseline BMI seem to have a positive correlation with the success of MAS therapy.Peer reviewe

Exclusion of PAX9 and MSX1 mutation in six families affected by tooth agenesis. A genetic study and literature review

Objectives: In the present study, it is described the phenotypical analysis and the mutational screening, for genes PAX9 and MSX1, of six families affected by severe forms of tooth agenesis associated with other dental anomalies and systemic entities. Study Design: Six families affected by severe tooth agenesis associated with other dental anomalies and systemic entities were included. Oral exploration, radiological examination, medical antecedents consideration and muta - tional screening for PAX9 and MSX1 were carried out. Results: No mutations were discovered despite the fact that numerous teeth were missing. An important pheno - typical variability was observed within the probands, not being possible to establish a parallelism with the pat - terns associated to previously described PAX9 and MSX1 mutations. Conclusions: These results bring us to conclude that probably other genes can determine phenotypical patterns of dental agenesis in the families studied, different than the ones described in the mutations of PAX9 and MSX1. Moreover, epigenetic factors can be involved, as those that can reduce gene dosage and other post-transcriptional modulation agents, causing dental agenesis associated or not with systemic anomalies

Candidate Gene Analysis of Tooth Agenesis Identifies Novel Mutations in Six Genes and Suggests Significant Role for WNT and EDA Signaling and Allele Combinations

Peer reviewe

An epidemiological study of dental agenesis in a primary health area in Spain: estimated prevalence and associated factors

Objectives: To evaluate the prevalence of dental agenesis and its possible association with other developmental dental anomalies and systemic entities. Setting and Sample Population: Descriptive transversal study, for which 1518 clinical records, of patients visited by the Odontological Service of the Primary Health Centre of Cassà de la Selva (Girona-Spain) between December 2002 and February 2006 were reviewed. The data were recorded in relation to the oral and dental anomalies and the associated systemic entities, between the ones referred as concomitant in literature. Results: Values of 9.48% (7.25% excluding the third molars) for dental agenesis and 0.39% for oligodontia were obtained. The presence of dental agenesis concomitant with some other forms of oral and dental anomalies was observed. Attention must be drawn to the fact that a greater number of concomitant systemic entities were observed in those patients that presented a severe phenotypical pattern of dental agenesis. Conclusions: The results of the present study do not differ from the ones reported in studies of similar characteristics among Occidental and Spanish populations. The relationship observed between certain systemic entities and developmental dental anomalies suggest a possible common genetic etiolog

Oral findings in Midline Syndrome: a case report and literature review

We describe a female patient with a midline syndrome. The patient presents agenesis of the corpus callosum, encephalocele, iris coloboma, hypertelorism, submucosal cleft palate and dental anomalies. Despite being very characteristic, her phenotypical traits do not coincide exactly with those reported to date in the literature. The karyotype and the molecular cytogenetic study do not show mutations. We identify the presence of dental anomalies in the mother and other family members, not being identified MSX1 and PAX9 mutations that could the related with their etiology. Despite the fact that dental agenesis has been related to a large number of other malformation syndromes and congenital conditions, dental anomalies have only rarely been mentioned when reporting midline syndromes. These dental phenotypical traits, present in the patient and her family, could be considered part of the midline syndrome in carriers as well as in the patients

Mutations in AXIN2 Cause Familial Tooth Agenesis and Predispose to Colorectal Cancer

Wnt signaling regulates embryonic pattern formation and morphogenesis of most organs. Aberrations of regulation of Wnt signaling may lead to cancer. Here, we have used positional cloning to identify the causative mutation in a Finnish family in which severe permanent tooth agenesis (oligodontia) and colorectal neoplasia segregate with dominant inheritance. Eleven members of the family lacked at least eight permanent teeth, two of whom developed only three permanent teeth. Colorectal cancer or precancerous lesions of variable types were found in eight of the patients with oligodontia. We show that oligodontia and predisposition to cancer are caused by a nonsense mutation, Arg656Stop, in the Wnt-signaling regulator AXIN2. In addition, we identified a de novo frameshift mutation 1994-1995insG in AXIN2 in an unrelated young patient with severe tooth agenesis. Both mutations are expected to activate Wnt signaling. The results provide the first evidence of the importance of Wnt signaling for the development of dentition in humans and suggest that an intricate control of Wnt-signal activity is necessary for normal tooth development, since both inhibition and stimulation of Wnt signaling may lead to tooth agenesis. Our findings introduce a new gene for hereditary colorectal cancer and suggest that tooth agenesis may be an indicator of cancer susceptibility

Panoramic radiographs of dentitions with tooth agenesis.

<p>Congenitally missing teeth are denoted with asterisks (*), and peg-shaped maxillary lateral incisors with arrows. All radiographs show many retained deciduous teeth. A. Dentition of a 15-year-old girl (family 219) with a heterozygous frameshift mutation K237SfsX2 in <i>MSX1</i>. All second premolars and third molars, maxillary first premolars and mandibular central incisors are missing. Maxillary lateral incisors are peg-shaped. <b>B</b>. 11-year-old girl (family 283) with a heterozygous missense mutation p. R47P in <i>PAX9</i> lacks all third molars, two maxillary second molars, three second premolars and mandibular central incisors. Left maxillary lateral incisor is peg-shaped. <b>C</b>. Severe tooth agenesis in a 13-year old boy (family 46) with a p.R357W mutation affecting the TNF domain of EDA. 10 permanent and 8 deciduous teeth, mostly in the anterior region, are missing. Maxillary left central incisor is conical. <b>D</b>. 19-year-old woman (family 266) lacks all third molars and lateral incisors, both maxillary canines, three second premolars and two deciduous lateral maxillary incisors. She was heterozygous for p.R325W in <i>EDAR</i>, p. S103F in <i>EDARADD</i> and p.G165R in <i>WNT10A</i>. <b>E</b>. Only 12 permanent teeth have developed in 27-year old woman (family 208) with a compound heterozygote mutations p.R113C and p.E194AfsX28 in <i>WNT10A</i>. Maxillary deciduous lateral incisors were also missing. <b>F</b>. 16-year old boy (family 261) with a heterozygous p.F228I variant in <i>WNT10A</i> lacks 13 permanent teeth including all third molars, mandibular second premolars, maxillary canines and five incisors.</p

Exclusion of PAX9 and MSX1 mutation in six families affected by tooth agenesis. A genetic study and literature review

Objectives: In the present study, it is described the phenotypical analysis and the mutational screening, for genes PAX9 and MSX1, of six families affected by severe forms of tooth agenesis associated with other dental anomalies and systemic entities. Study Design: Six families affected by severe tooth agenesis associated with other dental anomalies and systemic entities were included. Oral exploration, radiological examination, medical antecedents consideration and mutational screening for PAX9 and MSX1 were carried out. Results: No mutations were discovered despite the fact that numerous teeth were missing. An important phenotypical variability was observed within the probands, not being possible to establish a parallelism with the patterns associated to previously described PAX9 and MSX1 mutations. Conclusions: These results bring us to conclude that probably other genes can determine phenotypical patterns of dental agenesis in the families studied, different than the ones described in the mutations of PAX9 and MSX1. Moreover, epigenetic factors can be involved, as those that can reduce gene dosage and other post-transcriptional modulation agents, causing dental agenesis associated or not with systemic anomalies

Oral findings in Midline Syndrome: a case report and literature review

We describe a female patient with a midline syndrome. The patient presents agenesis of the corpus callosum, encephalocele, iris coloboma, hypertelorism, submucosal cleft palate and dental anomalies. Despite being very characteristic, her phenotypical traits do not coincide exactly with those reported to date in the literature. The karyotype and the molecular cytogenetic study do not show mutations. We identify the presence of dental anomalies in the mother and other family members, not being identified MSX1 and PAX9 mutations that could the related with their etiology. Despite the fact that dental agenesis has been related to a large number of other malformation syndromes and congenital conditions, dental anomalies have only rarely been mentioned when reporting midline syndromes. These dental phenotypical traits, present in the patient and her family, could be considered part of the midline syndrome in carriers as well as in the patients