Amelogenesis Imperfecta and Central Blindness: An Inherited Syndrome

Sensory organ and tooth development are not obviously linked. Two families characterized by Amelogenesis Imperfecta (AI) and Cone Rod Dystrophy leading to blindness have been previously described. Linkage to human chromosome 2q11 was reported in the larger family with the other exhibiting consistency with linkage to the same locus. The combination of a failure of normal dental biomineralisation and retinal degeneration poses intriguing questions as to the nature of the genetic defect(s) which specifically affects the development and function of these two highly specialised, yet diverse, tissues. Objective: This study aims to describe the phenotype of AI with CRD in four further families and establish if there are shared features that represent a novel syndrome. Methods: The dental and ocular phenotypes were assessed through clinical examination and supporting investigations. Ultrastructural analyses of deciduous teeth included scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) and transverse microradiography (TMR). Genotyping via Affymetrix 50k SNP chip and microsatellite markers allowed linkage analyses. Results: The clinical phenotypes were consistent between families, which originated from diverse ethnic backgrounds. AI involved the deciduous and permanent dentition with a generalized mixed hypoplastic and hypomature phenotype. Ultrastructural analyses of deciduous teeth from one individual identified hypomineralised enamel with poor structure. Visual impairment is evident from infancy with progressive loss of cone and rod function and deterioration of colour and central vision to the point of blindness by the age of 20 years-old. Linkage or consistency with linkage to chromosome 2q11 were confirmed in the three families suitable for these analyses. Studies are ongoing to identify the gene responsible for this unusual combination of clinical phenotypes. Conclusions: Six families of diverse ethnic origins have been identified that share common features consistent with a genetically homogenous syndrome characterized by AI and CRD.