Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting

Abstract

Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ2 statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10−8) and permanent dentitions (51% vs. 8%, P = 4 × 10−62) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions.

Dental crown symmetry in unilateral cleft lip and palate patients: A three‐dimensional analysis on digital dental models

“…So far, there has been no study with high evidential levels that revealed the genetic relationship between the formation of cleft lip and palate and development of dental anomalies in CLP patients. According to Howe et al, dental characteristics may result from local mechanical circumstances at the time of cleft formation or from conditions of blood supply during early postnatal surgical interventions. A meta‐analysis study that was carried out in 2013 determined that the incisor and premolar teeth on the cleft side were larger, but there was no significant difference in the other teeth .…”

Testing the face shape hypothesis in twins discordant for nonsyndromic orofacial clefting

“…These subclinical phenotypes are considered to be an incomplete expression of underlying susceptibility loci for orofacial clefting (Gottesman & Gould, ; Weinberg et al, ). Several such subclinical phenotypes have now been described (Roosenboom et al, ,), such as mild disruption of the upper lip musculature (Neiswanger et al, ), the appearance of “whorls” on the surface of the lower lip (Neiswanger et al, ), dental anomalies (Howe et al, ), and altered facial shape (Roosenboom et al, ,; Weinberg et al, , ).…”

Rare and Common Variants Conferring Risk of Tooth Agenesis

“…The function of FAM49A is not well described; however, a recent study showed expression of Fam49a during mouse development in the palatal mesenchymal cells and epithelium cells (Yu et al 2017). High prevalence of various dental anomalies in children with OFC has been reported (Howe et al 2015). The maxillary lateral incisors are more commonly missing from subjects with OFC than from controls (Howe The new signal (NOL11) from the GWAS of maxillary second premolars is indicated in blue.…”