Associations Between Dental Anomalies and Ocular Diseases

Not yet recruiting

• Conditions: Congenital Cataract; Tooth Abnormalities; Ocular Pathologies

• Registration Number: NCT06950619
• Lead Sponsor: University of Pavia

Brief Summary

Considering recent literature, a possible link between ocular diseases and dental anomalies could be hypothesized, given the existence of shared genetic and developmental mechanisms between these two anatomical districts. Both the eye and the teeth develop from ectodermal and mesenchymal tissues, involving common molecular signaling pathways such as Wnt, BMP, and Pax. Some syndromic forms of congenital cataract, such as the X-linked conditions of Nance-Horan syndrome (NHS - MIM #302350) and oculo-facio-cardio-dental syndrome (OFCD - MIM #300166) often include dental abnormalities, such as Hutchinson's incisors ('screwdriver-shaped') and numerical defects (from dental agenesis to oligodontia). In a previous cohort study on congenital cataract, we observed that individuals carrying variants in genes associated with non-syndromic and syndromic forms of congenital cataract (e.g. PAX6) also had dental abnormalities (mainly number defects). This evidence led us to hypothesise a deeper link between oculogenesis and dental abnormalities.

Detailed Description

Considering recent literature, a possible link between ocular diseases and dental anomalies could be hypothesized, given the existence of shared genetic and developmental mechanisms between these two anatomical districts. Both the eye and the teeth develop from ectodermal and mesenchymal tissues, involving common molecular signaling pathways such as Wnt, BMP, and Pax. Genetic variants affecting these pathways may therefore result in combined phenotypes, such as congenital cataract associated with tooth agenesis or enamel malformations.

Certain rare genetic syndromes, such as Nance-Horan syndrome and Oculo-Facio-Cardio-Dental syndrome (OFCD), support the hypothesis of a systemic correlation between odontogenesis and eye development. In a previous study on congenital cataract, almost 10% of probands with variants in BCOR, CWC27, IFIH1, NHS, and PAX6, various dental anomalies were observed. Therefore, exploring the possible connection between ocular and dental diseases may not only facilitate early and multidisciplinary diagnosis but also open new perspectives in genetic research and the development of personalized therapeutic approaches, for which Whole Genome Sequencing seems the first choice option to investigate non-syndromic forms.

Therefore, the current observational study aims at identifying variants in common genes for ocular pathologies and dental anomalies (agenesis, supernumeraries, Hutchinson teeth, Mulberry molars) in orthodontic patients with family history of ocular manifestations, to hypothesize a deeper connection between teeth and eyes. An electronic search will be performed on the database of the Unit of Orthodontics and Pediatric Dentistry, Section of Dentistry, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences of the University of Pavia to find patients presenting tooth abnormalities. Patients will be contacted by phone to collect information on their family history of ocular pathology. If the anamnesis will be positive, they will be invited to be enrolled in the study, and a buccal swab will be perfomed to collect DNA sample that will be analysed with Next Generation Sequencing. Additionally, skeletal patterns will be evaluated through cephalometric analysis if lateral cephalometric radiographs will be present. As secondary outcome, anomalies on skin appendages will be evaluated, considering the common ectodermal origin between skin and teeth.

Study Timeline

• Study First Submitted: 2025-04-21
• Study First Submitted QC: 2025-04-21
• Study First Posted: 2025-04-30
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-10
• Last Update Posted: 2025-06-13
• Study Start: 2025-09
• Primary Completion: 2027-09
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• Supernumerary teeth
• oligodontia
• screw driver sharped incisors
• Hutchinson's teeth
• mulberry molars
• tooth agenesis
• congenital cataract, keratitis, keratoconus, corneal dystrophies, ectopia lentis, glaucoma, retinitis pigmentosa, coloboma and aniridia in probands or relatives
• skin appendages anomalies in probands or relatives

Exclusion Criteria

• Previous orthodontic, restorative, endodontic, prosthetic and surgical treatment that could alter tooth morphology and position

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Presence of variants in common genes for congenital cataract and/or ocular diseases and dental anomalies	Baseline	Whole Genome Sequencing will be used to find pathogenetic variants

Secondary Outcome Measures

Name	Time	Method
SNA angle	Baseline	Angle between the sella, nasion and A point measured on lateral cephalometric radiograph
ANB angle	Baseline	Angle between point A, the nasion and point B measured on lateral cephalometric radiograph
ANS-PNS plane	Baseline	Bispinal plane traced between the anterior nasal spine (ANS) and the posterior nasal spine (PNS) measured on lateral cephalometric radiograph
SNB angle	Baseline	Angle between the sella, nasion and B point measured on lateral cephalometric radiograph
SN plane	Baseline	Plane between the sella point S and nasion point N measured on lateral cephalometric radiograph
Sella turcica length	Baseline	Distance between the Tuberculum sellae (TS) and the dorsum sella measured on lateral cephalometric radiograph
Sella turcica diameter	Baseline	Distance between the Tuberculum Sellae (TS) and the farthest point on the inner wall of the sella measured on lateral cephalometric radiograph
Sella turcica depth	Baseline	The distance of a line dropped perpendicularly from the interclinoidal distance to the deepest point of the sella floor measured on lateral cephalometric radiograph
Presence of variants in common genes for keratitis, keratoconus, corneal dystrophies, ectopia lentis, glaucoma, retinitis pigmentosa, coloboma and aniridia will be analysed.	Baseline	Whole Genome Sequencing will be used to find pathogenetic mutations
GoGn plane	Baseline	Mandibular plane traced between Gonion and Gnathion points measured on lateral cephalometric radiograph
Presence of variants in skin appendages anomalies will be also evaluated for ascertaining ectodermal diplasia.	Baseline	Whole Genome Sequencing will be used to find pathogenetic mutations

Trial Locations

Locations (2)

Unit of Medical Genetics, Department of Molecular Medicine, University of Pavia; 🇮🇹 Pavia, Lombardy, Italy

Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia; 🇮🇹 Pavia, Lombardy, Italy