Clinical trial NCT06950619: Associations Between Dental Anomalies and Ocular Diseases
Official title: Associations Between Dental Anomalies and Ocular Diseases: Observational Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Congenital Cataract
Tooth Abnormalities
Ocular Pathologies
Lead sponsor: University of Pavia
Sponsor class: OTHER
First posted: 2025-04-30
Enrollment: 5
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Orthodontic patients undergone orthopedic/orthodontic treatment and fulfilling inclusion criteria.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Presence of variants in common genes for congenital cataract and/or ocular diseases and dental anomalies
timeFrame: Baseline
Secondary outcomes:
measure: SNA angle
timeFrame: Baseline
measure: SNB angle
timeFrame: Baseline
measure: ANB angle
timeFrame: Baseline
measure: SN plane
timeFrame: Baseline
measure: ANS-PNS plane
timeFrame: Baseline
measure: GoGn plane
timeFrame: Baseline
measure: Sella turcica length
timeFrame: Baseline
measure: Sella turcica diameter
timeFrame: Baseline
measure: Sella turcica depth
timeFrame: Baseline
measure: Presence of variants in common genes for keratitis, keratoconus, corneal dystrophies, ectopia lentis, glaucoma, retinitis pigmentosa, coloboma and aniridia will be analysed.
timeFrame: Baseline
measure: Presence of variants in skin appendages anomalies will be also evaluated for ascertaining ectodermal diplasia.
timeFrame: Baseline
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Unit of Medical Genetics, Department of Molecular Medicine, University of Pavia
state: Lombardy
city: Pavia
country: Italy
facility: Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia
state: Lombardy
Study officials:
affiliation: University of Pavia
name: Andrea Scribante
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lecca M, Mauri L, Gana S, Del Longo A, Morelli F, Nicotra R, Plumari M, Galli J, Sirchia F, Valente EM, Cavallari U, Mazza M, Signorini S, Errichiello E. Novel molecular, structural and clinical findings in an Italian cohort of congenital cataract. Clin Genet. 2024 Oct;106(4):403-412. doi: 10.1111/cge.14568. Epub 2024 Jun 5.