The Quebec Dental Anomalies Registry: Identifying genes for rare disorders

Abstract

There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.

Keywords: craniofacial anomalies; genetics; oligodontia; pediatric dentistry.

Fig. 1.

Cone beam imaging of a homozygous TSPEAR variant c.974delC; p.Ser325Ter in Individual 1, Family 10, TS1. Panoramic view A) and volume rendering B) of the dental arches. Severe oligondontia with 12 missing teeth; cone-like shapes of the lower canines (#33 and #43) and upper first premolars (#14 and #24).

Fig. 2.

Cone beam imaging of a heterozygous PRKAR1A variant c.379_380delinsTT; p.Ala127Phe in Individual 1, Family 12, TS1. Volume rendering of the upper dental arch A) and buccolingual slices passing, respectively, through the upper central incisors (#11–21). Transposition tendency of germs #15 and #25; B) root abnormalities with short root portions of teeth #11–21.