Genetics of Congenital Cataracts

Abstract The term “congenital cataract” refers to a lens opacity that is present in the first year of life. Congenital cataracts account for about 10% of cases of childhood blindness.1 In developed countries congenital cataracts are mostly inherited, affecting approximately 30 cases for every 100,000 births.2 Prenatal rubella, among other infectious causes, accounts for most of congenital cataracts in the developing countries.3 Inherited cataracts are most often “isolated,” although the association with other ocular and systemic abnormalities (as seen in association with developmental and chromosomal defects) is not uncommon. According to OMIM (Online Mendelian Inheritance in Man; http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim) cataracts are mentioned in 344 “hits,” which include numerous syndromes. Genetically determined cataracts are most often inherited as autosomal dominant traits, although autosomal and X-linked recessive inheritance patterns have been documented.4,5,6 A classification of the most frequent subtypes of congenital cataracts is provided in Table 19.1. The crystalline lens is an avascular and transparent structure, which allows focusing of the light on the retina. The transparency of the lens is maintained through complex molecular mechanisms occurring during and after its development. Any deregulation in these mechanisms leads to loss of transparency of the lens, resulting in variable degrees of opacification. Late detection of early-onset cataracts can result in irreversible loss of vision. The past two decades have provided an extensive amount of information on the genetics of inherited cataracts, which present a significant degree of genetic heterogeneity.2,7 This chapter reviews the recent advances of the molecular mechanisms and defects underlying inherited cataracts by concentrating on the genetics of congenital and age-related cataracts. This new knowledge contributes to a better understanding of biologic pathways and may eventually contribute to improved management of this cause of vision loss. Congenital cataracts due to other causes, such as infection (rubella, syphilis, toxoplasmosis), trauma, and drugs, will not be discussed.