Associations Between Congenital Cataract and Dental Anomalies

Congenital cataract (CC) is the leading cause of treatable childhood blindness and reduced vision worldwide, with a global prevalence of 4.24/10,000 and significant ethnic variations. In most cases it occurs in isolation, and more rarely with other ocular or systemic features. Some syndromic forms of CC, 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 CC, we observed that individuals carrying variants in genes mainly associated with non-syndromic forms of CC (e.g. PAX6) also had dental abnormalities (mainly number defects). This evidence led us to hypothesise a deeper link between cataractogenesis and dental abnormalities, not limited exclusively to syndromic forms of CC.

Congenital cataract (CC) is the major cause of treatable childhood blindness and impaired vision worldwide, with a global prevalence of 4.24/10 000. The diagnosis of CC can be performed after a few years of life. In general, CC manifests isolatedly, more rarely with other ocular pathologies (coloboma, microcornea, aniridia, persistent foetal vasculature, anterior segment defects, retinal defects and microphthalmia) or systemic features. Most CC cases are idiopathic, whereas hereditary forms account for about one fourth. Unilateral CC is more commonly found in idiopathic forms, while bilateral CC is more often found in hereditary forms.

About 100 genes and more are involved in hereditary CC, with a prevalent autosomal dominant pattern of inheritance. Lens proteins (crystallins) are frequently involved .

Hereditary CC is caused by alterations in more than 100 genes, mostly following an autosomal dominant pattern of inheritance and frequently coding for lens proteins, namely crystallins. The challenge in the diagnosis of CC is due to clinical and genetic heterogeneity, overlapping phenotypes, and gene pleiotropy. Exome sequencing (ES) has been adopted to investigate single or few pedigrees, whereas more rarely in larger CC cohorts. A previous study found various mutated genes in a cohort of CC patients, among which:

* NHS with microdontia, oligodontia, supernumerary teeth, screw-driver incisors and mulberry molars;
* BCOR with supernumerary teeth;
* PAX6 with tooth agenesis.

The first two genes are associated respectively with Nance-Horan syndrome and Oculo-facio-cardio-dental (OFCD) syndrome, while PAX6 is associated with non-syndromic forms of CC.

Therefore, the current cross-sectional observational study aims at identifying novel mutations in common genes for CC and dental anomalies (agenesis, supernumeraries, Hutchinson teeth, morphiform molars) in orthodontic patients with personal or parental history of ocular and cutaneous manifestations, to hypothesize a deeper connection between cataractogenesis and odontogenesis, not limited exclusively to syndromic forms of CC. Additionally, skeletal patterns will be evaluated through cephalometric analysis.

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