Genetic Analysis Of Congenital Cataracts.

ABSTRACT

Congenital cataracts constitute a major cause of blindness in infancy. It is caused by the loss of transparency of the lens, hampering normal vision. Affected infants become visually handicapped necessitating effective management. Cataracts result when normal lens formation during embryogenesis and its subsequent development are affected. Based on the location and morphology of the opacities, different phenotypic forms of cataracts are identified which are under the control of different genes and follow autosomal dominant, autosomal recessive and X-linked inheritance. Crystallins (a, b and g) which constitute 90% of the water soluble proteins are responsible for the maintenance of the refractive property of the lens. Hence structural variations in these proteins have been associated with cataracts. Intrinsic membrane proteins which are water insoluble and expressed in the terminal differentiation of the lens epithelium are also implicated in cataract formation. Cataracts are found to be associated with maternal infections during pregnancy (rubella infection), several clinical syndromes, metabolic disorders, chromosomal disorders, (triploidy, trisomies, monosomy, deletions, duplications and translocations), and gene disorders. Autosomal dominant forms are found to be more common among the gene disorders and exhibit intrafamilial, interfamilial and interocular variations. More than a dozen genes have been mapped for cataracts showing the locus and allelic heterogeneity and two of them are associated with mutations in the crystallin genes. One of them with over expression of gE gene on chromosome 2 causes Coppock like cataract while a chain termination mutation in the crystallin BB2 locus on chromosome 22 causes Cerulean cataract. Experiments on animals suggest crystallins as strong candidates for the study of cataracts in man. Other candidate loci include intrinsic membrane proteins (MIP), developmental genes (PAX6) and connexin gap junction proteins (CX46). Surgical extraction of cataracts though is considered as the best treatment for cataracts, the prognosis is poor when it comes to infantile forms. Hence risk predictions and counseling based on the mode of inheritance and other factors seems to be the best approach in the management of cataracts. Recently prenatal detection of cataracts through ultrasonography has been reported which can be made a part of the routine anatomical study specially when family history for severe genetic disorder assoicated with cataracts exist.