Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes.

BACKGROUND: Oral clefts, that is, clefts of the lip and/or cleft palate (CL/P), are the most common craniofacial birth defects with an approximate incidence of ~1/700. To date, physicians stratify patients with oral clefts into either syndromic CL/P (syCL/P) or non-syndromic CL/P (nsCL/P) depending on whether the CL/P is associated with another anomaly or not. In general, patients with syCL/P follow Mendelian inheritance, while those with nsCL/P have a complex aetiology and, as such, do not adhere to Mendelian inheritance. Genome-wide association studies have identified approximately 30 risk loci for nsCL/P, which could explain a small fraction of heritability. METHODS: To identify variants causing nsCL/P, we conducted whole exome sequencing on 84 individuals with nsCL/P, drawn from multiplex families (n=46). RESULTS: We identified rare damaging variants in four genes known to be mutated in syCL/P: TP63 (one family), TBX1 (one family), LRP6 (one family) and GRHL3 (two families), and clinical reassessment confirmed the isolated nature of their CL/P. CONCLUSION: These data demonstrate that patients with CL/P without cardinal signs of a syndrome may still carry a mutation in a gene linked to syCL/P. Rare coding and non-coding variants in syCL/P genes could in part explain the controversial question of 'missing heritability' for nsCL/P. Therefore, gene panels designed for diagnostic testing of syCL/P should be used for patients with nsCL/P, especially when there is at least third-degree family history. This would allow a more precise management, follow-up and genetic counselling. Moreover, stratified cohorts would allow hunting for genetic modifiers.

Craniofacial characteristics in the sagittal dimension: A cephalometric study in Lebanese young adults.

OBJECTIVES: The purpose of this study was to assess the sagittal cephalometric characteristics of young adult Lebanese individuals and assess gender-related differences. MATERIALS AND METHODS: Conventional lateral cephalograms were obtained from 117 subjects. Eight linear/angular measurements combining sagittal parameters selected form McNamara and Steiner analyses were recorded. Paired t-test was applied to evaluate differences between genders and skeletal classes. RESULTS: Males showed significantly greater maxillary and mandibular length than females. ANB was larger in females with no significant differences in SNA values indicating that Lebanese females tend to have a more convex profile than their male counterparts. Subjects with skeletal Class III tended to have a retrognathic maxilla rather than a prognathic mandible. CONCLUSIONS: Sexual dimorphism is evident in young Lebanese adults relative to linear skeletal dimensions regardless of the skeletal class. Skeletal determinants of Class III malocclusions may be different from those of other population groups.

Alveolar osseous distraction by the combined use of modified miniplates and an orthodontic appliance. A technical note.

An original alveolar osseous distraction method using a Hyrax orthodontic device connected to two miniplates modified as a skeletal orthodontic anchorage (Bollard™ type) is reported and illustrated by three cases. In all three cases with alveolar bone insufficiency, the alveolar osseous distraction allowed for dental implant positioning and fixed dental prosthetic rehabilitation.