Associations Between Dental Anomalies and Ocular, Cutaneous and Skin Appendages Features

A Clinical Investigation Into the Co-occurrence of Dental Anomalies With Ocular and Cutaneous Features

Considering recent literature, it is possible to hypothesise a link between dental anomalies and ocular and/or cutaneous findings, given the existence of shared genetic and developmental mechanisms between these two anatomical areas. Both the eye and teeth develop from ectodermal and mesenchymal tissues, involving common molecular signalling pathways such as Wnt, BMP and PAX. Genetic variants affecting these pathways can therefore determine combined phenotypes, such as congenital cataracts associated with dental agenesis or enamel malformations. Some rare genetic syndromes, such as Nance-Horan syndrome and oculofacio-cardio-dental (OFCD) syndrome, support the hypothesis of a systemic correlation between odontogenesis and ocular development. In a previous study on congenital cataracts, nearly 10% of probands with variants in the BCOR, CWC27, IFIH1, NHS, and PAX6 genes had various dental abnormalities. Therefore, exploring the possible connection between eye and dental diseases may not only facilitate early and multidisciplinary diagnosis, but also open up new perspectives in genetic research and the development of personalised therapeutic approaches, for which whole genome sequencing (WGS) appears to be the first choice for investigating non-syndromic forms. Therefore, the current clinical study aims to identify variants in genes common to eye diseases and dental anomalies (agenesis, supernumerary teeth, Hutchinson's teeth, mulberry molars) in orthodontic patients over the age of 12 with dental anomalies who are about to begin orthodontic treatment or who are attending routine check-ups at the Orthodontics and Paediatric Dentistry Unit, Department of Clinical, Surgical, Diagnostic and Paediatrics Sciences at the University of Pavia who have a family history of ocular and cutaneous manifestations or presenting at the same time dental, ocular and/or cutaneous anomalies. Patients who are eligible will be invited to participate in the study. After signing the informed consent form, the Case Report Form will be completed to collect the data of interest for the study; previous medical reports will be asked to patients or parents/legal guardians in case of minors to ascertain ocular and cutaneous pathologies; a buccal swab will be taken to collect a DNA sample that will be analysed with Next Generation Sequencing. In addition, cephalometric evaluations will be performed if lateral teleradiographs will be available, if already performed in accordance with Good Clinical Practice for the purposes of orthodontic assessment of patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Tooth Abnormalities; Congenital Cataract; Ocular Pathologies
• Intervention / Treatment: Other: Cephalometric tracing; Genetic: Whole Genome Sequencing

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. The same procedure will be performed with patients presenting for oral care at the same Unit prospectively. 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 Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea Scribante; Phone Number: +39 0382516223; Email: andrea.scribante@unipv.it

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Unit of Orthodontics and Pediatric Dentistry - Section of Dentistry - Department of Clinical, Surgical, Diagnostic and Pediatrics - University of Pavia
      • Contact: Maurizio Pascadopoli, PhD; Phone Number: +39 0382516223; Email: maurizio.pascadopoli01@universitadipavia.it
    • Pavia, Lombardy, Italy, 27100
      • Unit of Medical Genetics, Department of Molecular Medicine, University of Pavia
      • Contact: Edoardo Errichiello, PhD; Email: edoardo.errichiello@unipv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Study Population

Orthodontic patients undergone orthopedic/orthodontic treatment and fulfilling inclusion criteria.

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Orthodontic patients; Patients fulfilling the inclusion criteria will undergo blood sampling

Other: Cephalometric tracing; Cephalometric tracing will be performed on lateral cephalometric radiographs if present and not taken on purpose for the study; Genetic: Whole Genome Sequencing; Genetic testing will be performed to find variants in genes involving congenital cataract and/or ocular diseases (keratitis, keratoconus, corneal dystrophies, ectopia lentis, glaucoma, retinitis pigmentosa, coloboma and aniridia) and dental anomalies (tooth agenesis, supernumerary teeth, Hutchinson teeth, mulberry molars). Cutaneous appendage anomalies will be also evaluated in clinical history for ascertaining ectodermal diplasia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of variants in common genes for dental anomalies, ocular diseases and cutaneous/skin appendages features	Whole Genome Sequencing will be used to find pathogenetic variants	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SNA angle	Angle between the sella, nasion and A point measured on lateral cephalometric radiograph	Baseline
SNB angle	Angle between the sella, nasion and B point measured on lateral cephalometric radiograph	Baseline
ANB angle	Angle between point A, the nasion and point B measured on lateral cephalometric radiograph	Baseline
SN plane	Plane between the sella point S and nasion point N measured on lateral cephalometric radiograph	Baseline
ANS-PNS plane	Bispinal plane traced between the anterior nasal spine (ANS) and the posterior nasal spine (PNS) measured on lateral cephalometric radiograph	Baseline
GoGn plane	Mandibular plane traced between Gonion and Gnathion points measured on lateral cephalometric radiograph	Baseline
Sella turcica length	Distance between the Tuberculum sellae (TS) and the dorsum sella measured on lateral cephalometric radiograph	Baseline
Sella turcica diameter	Distance between the Tuberculum Sellae (TS) and the farthest point on the inner wall of the sella measured on lateral cephalometric radiograph	Baseline
Sella turcica depth	The distance of a line dropped perpendicularly from the interclinoidal distance to the deepest point of the sella floor measured on lateral cephalometric radiograph	Baseline

Collaborators and Investigators

• Sponsor: University of Pavia
• Investigators: Principal Investigator: Andrea Scribante, University of Pavia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 21, 2025
• First Submitted That Met QC Criteria: April 21, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Tooth Abnormalities; Investigative Techniques; Genetic Techniques; Sequence Analysis; Sequence Analysis, DNA; Whole Genome Sequencing
• Other Study ID Numbers: 2025-DENTALOCULARANOMALIES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be available upon motivated request to the Principal Investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No