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Background Dental agenesis is the most common, often heritable, developmental anomaly in humans. Mutations in MSX1, PAX9, AXIN2 and the ectodermal dysplasia genes EDA, EDAR and EDARADD have been detected in familial severe tooth agenesis. However, until recently, in the majority of cases (similar to 90%) the genetic factor could not be identified, implying that other genes must be involved. Recent insights into the role of Wnt10A in tooth development, and the finding of hypodontia in carriers of the autosomal recessive disorder, odontooncychodermal dysplasia, due to mutations in WNT10A (OMIM 257980; OODD), make WNT10A an interesting candidate gene for dental agenesis.Methods In a panel of 34 patients with isolated hypodontia, the candidate gene WNT10A and the genes MSX1, PAX9, IRF6 and AXIN2 have been sequenced. The probands all had isolated agenesis of between six and 28 teeth.Results WNT10A mutations were identified in 56% of the cases with non-syndromic hypodontia. MSX1, PAX9 and AXIN2 mutations were present in 3%, 9% and 3% of the cases, respectively.Conclusion The authors identified WNT10A as a major gene in the aetiology of isolated hypodontia. By including WNT10A in the DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in this condition was significantly increased from 15% to 71%.

Background Oral clefts—comprising cleft lip (CL), cleft lip with cleft palate (CLP), and cleft palate (CP)—are being diagnosed prenatally more frequently. Consequently, the need for accurate information on the risk of associated anomalies and chromosomal defects to aid in prenatal counselling is rising. This systematic review was conducted to investigate the prenatal and postnatal prevalence of associated anomalies and chromosomal defects related to cleft category, thereby providing a basis for prenatal counselling and prenatal invasive diagnostics. Methods Online databases were searched for prenatal and postnatal studies on associated anomalies and chromosomal defects in clefts. Data from the literature were complemented with national validated data from the Dutch Oral Cleft Registry. Results Twenty studies were included: three providing prenatal data, 13 providing postnatal data, and four providing both. Data from prenatal and postnatal studies showed that the prevalence of associated anomalies was lowest in CL (0–20.0% and 7.6–41.4%, respectively). For CLP, higher frequencies were found both prenatally (39.1–66.0%) and postnatally (21.1–61.2%). Although CP was barely detectable by ultrasound, it was the category most frequently associated with accompanying defects in postnatal studies (22.2–78.3%). Chromosomal abnormalities were most frequently seen in association with additional anomalies. In the absence of associated anomalies, chromosomal defects were found prenatally in CLP (3.9%) and postnatally in CL (1.8%, 22q11.2 deletions only), CLP (1.0%) and CP (1.6%). Conclusions Prenatal counselling regarding prognosis and risk of chromosomal defects should be tailored to cleft category, and more importantly to the presence/absence of associated anomalies. Irrespective of cleft category, clinicians should advise invasive genetic testing if associated anomalies are seen prenatally. In the absence of associated anomalies, prenatal conventional karyotyping is not recommended in CL, although array comparative genomic hybridisation should be considered. In presumed isolated CLP or CP, prenatal invasive testing, preferably by array based methods, is recommended.