Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. We ascertained eight families affected by HS and, by using a whole-exome sequencing approach, identified biallelic mutations in PEX1 or PEX6 in six of them. Loss-of-function mutations in both genes are known causes of a spectrum of autosomal-recessive peroxisome-biogenesis disorders (PBDs), including Zellweger syndrome. PBDs are characterized by leukodystrophy, hypotonia, SNHL, retinopathy, and skeletal, craniofacial, and liver abnormalities. We demonstrate that each HS-affected family has at least one hypomorphic allele that results in extremely mild peroxisomal dysfunction. Although individuals with HS share some subtle clinical features found in PBDs, the diagnosis was not suggested by routine blood and skin fibroblast analyses used to detect PBDs. In conclusion, our findings define HS as a mild PBD, expanding the pleiotropy of mutations in PEX1 and PEX6.

We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9. A pair of identical twins affected with hypodontia in a third family demonstrated a 288-bp insertion within exon 2 that resulted in a putative frameshift mutation and a premature stop codon. The insertion was associated with the loss of 7-bp from exon 2. A block of 256-bp of sequence within the insertion was completely identical to downstream sequence from the second intron of the PAX9 gene. These studies extend the spectrum of mutations in PAX9 associated with hypodontia to include heretofore undescribed categories, including missense mutations.

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Molar incisor hypomineralisation (MIH) is a common enamel condition, presenting with incisor opacities, which may be of psychosocial concern to children. This clinical study sought to determine whether minimally invasive treatment, aiming to improve incisor aesthetics, would also improve children’s oral health-related quality of life (OHRQoL). 111 MIH patients, aged 7–16 years, referred to a UK Dental Hospital, were invited to complete the Child Oral Health Impact Profile (C-OHIP-SF19) prior to any intervention (T0) and again at one-month following the intervention (T1) for MIH. Treatment regimens included one or more of the following: Microabrasion; resin infiltration; tooth whitening; resin composite restoration. Data were obtained for 93 children with a mean age of 11 years. Mean total C-OHIP-SF19 score at T0 was 47.00 (SD = 9.29; range = 0–76) and this increased significantly at T1 to 58.24 (SD = 9.42; range = 0–76; p < 0.001, paired t-test), indicating a marked improvement in self-reported OHRQoL. There were no statistically significant differences according to gender. This is the first study to show that simple, minimally invasive dental treatment, to reduce the visibility of enamel opacities, in MIH, can have a positive impact on children’s wellbeing.

Determinants of children's oral health-related quality of life following aesthetic treatment of enamel opacities

A multifactorial model based on an underlying continuous distribution of tooth size, with thresholds determining hypodontia and supernumeraries, has been proposed [1]. Our aim is to investigate this model by comparing tooth morphology of affected patients and their first degree relatives with normal controls. An image analysis system [2] was used to measure teeth on study models of controls, patients with hypodontia of varying degrees and location, first-degree relatives of hypodontia index cases, and patients with supernumerary teeth in the maxillary incisor region. Mesio-distal crown size in hypodontia patients was smaller than controls, and this difference was significant for all tooth types. There was a general pattern: the more severe the hypodontia, the smaller the size of the tooth formed. Patients with supernumerary teeth had permanent maxillary central and lateral incisors and canines that were significantly larger in mesio-distal width than controls. The maxillary central incisors also differed in taper in supernumerary patients compared to controls. Hypodontia prevalence was higher in first-degree relatives (22%) of hypodontia index cases than in the general population (4.4%), and unaffected relatives had smaller teeth than controls. Thus, there were generalized and localized effects within the dentition, and these findings are compatible with the statistical expectations of the proposed multifactorial model.

This new system provided accurate quantitative measurements of dental plaque and labial tooth surfaces and was shown to have increased sensitivity when compared with the Turesky modification of the Quigley and Hein plaque index and the Addy plaque area index. The stored images can be re-measured for reliability and comparability between studies.