Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Tooth agenesis patterns and phenotype variation in a cohort of Belgian patients with hypodontia and oligodontia clustered in 79 families with their pedigrees.

BACKGROUND: Even though tooth agenesis is the most common developmental anomaly of the human dentition, its genetic background and pathogenic mechanism(s) still remain poorly understood. Syndromic and isolated forms of hypodontia have been described and can occur sporadically or in families. OBJECTIVES: We describe and analyse the hypo-/oligodontia phenotype variations in families. The index patient suffers from severe or mild hypodontia; case-parents/sib records are available. Furthermore, we aim to evaluate whether the different agenesis patterns in the pedigrees are predictive of mutations in specific genes based on reported genotype-phenotype associations. MATERIALS AND METHODS: Dental records and pedigrees were collected from 79 families. In 67 families, the index patient presented with oligodontia while in 12 families with hypodontia. The phenotype data of 66 oligodontia index patients were analysed with the Tooth Agenesis Code software. RESULTS: Nine families counted two members; one family counted three members affected with oligodontia. Twenty-four oligodontia families respectively had one (n = 17), two (n = 4), three (n = 2) or four (n = 1) additional family members presenting with hypodontia. Of the 77 oligodontia cases, two showed the same tooth agenesis pattern, while 75 patients showed unique tooth agenesis patterns. CONCLUSIONS: Despite familial aggregation and expected Mendelian segregation, the number of missing teeth in the familial hypo-/oligodontia phenotypes and the tooth agenesis patterns are highly variable between the affected family members. Therefore, we hypothesize that tooth agenesis is not (always) a simple monogenic condition, but additional genetic or environmental factors can modify the expression of the phenotype.

Orthodontic and orthognathic management of a patient with Apert syndrome: a case report.

This case report describes the combined orthodontic and orthognathic management of a 14-year-old girl affected with Apert syndrome. She presented with a severe Class III skeletal relationship, midfacial hypoplasia and an large anterior open bite. Intraorally, she had severe crowding, a narrow maxilla and lateral posterior crossbites. The patient was treated with a combination of removable and fixed appliances, a transpalatal skeletal distractor and Le Fort I surgery. The extraoral characteristics improved and a good occlusal relationship between maxillary and mandibular teeth was achieved.

The effect of using CBCT in the diagnosis of canine impaction and its impact on the orthodontic treatment outcome.

AIM: To investigate the added-value of using CBCT in the orthodontic treatment method of maxillary impacted canines and treatment outcome. MATERIALS AND METHODS: The sample consisted of 118 treated patients. The CBCT group (n = 58) (39 females/19 males with the mean age of 14.3 years) included those with conventional treatment records consisting of panoramic and cephalometric radiographs, intra-and extra-oral photographs, and dental casts and complemented with a CBCT scan for additional diagnostic information. The conventional group (n = 60) (31 females/29 males with mean age 13.1 years) included those with similar conventional treatment records but without CBCT imaging. RESULTS: There were significant differences in the canine-related variables between both groups. The CBCT group had the higher level of difficulty and more severely displaced canines when compared with the conventional group. However, no significant difference was found between groups either in the number of treatment methods used or in the use of interceptive methods combined with other treatment modalities or choice of extraction versus non-extraction. In terms of treatment success and interval duration, no significant differences were found. However, treatment duration was significantly (4 months) shorter in the CBCT group compared with the conventional group (P = 0.023). CONCLUSION: CBCT has been used in cases with more severe symptoms of maxillary canine impaction. The use of CBCT improved the diagnostic capabilities and improved the chances of success in the more difficult cases to a level similar to that of simpler cases treated on the basis of 2D information.