Congenital Cataract, Ocular Pathologies, Tooth Abnormalities
Conditions
Brief summary
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.
Interventions
GENETICWhole 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.
OTHERCephalometric tracing
Cephalometric tracing will be performed on lateral cephalometric radiographs if present and not taken on purpose for the study
Sponsors
University of Pavia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of variants in common genes for dental anomalies, ocular diseases and cutaneous/skin appendages features | Baseline | Whole Genome Sequencing will be used to find pathogenetic variants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SNB angle | Baseline | Angle between the sella, nasion and B point measured on lateral cephalometric radiograph |
| ANB angle | Baseline | Angle between point A, the nasion and point B measured on lateral cephalometric radiograph |
| SN plane | Baseline | Plane between the sella point S and nasion point N 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 |
| SNA angle | Baseline | Angle between the sella, nasion and A point 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 |
| GoGn plane | Baseline | Mandibular plane traced between Gonion and Gnathion points measured on lateral cephalometric radiograph |
Countries
Italy
Contacts
Primary ContactAndrea Scribante
Outcome results
None listed