Environmental risk factors in congenital malformations of the eye

Abstract

Developmental eye defects such as coloboma are a significant cause of visual morbidity in children, and are more common in India than elsewhere. The possible role of environmental factors in the aetiology of these conditions was investigated by studying birth order, symptoms of vitamin A deficiency (night blindness), drug use and maternal illness in pregnancy, rubella antibodies and exposure to agricultural chemicals. Through hospital records and community-based rehabilitation programmes in Andhra Pradesh, children with colobomata were recruited from schools for the blind. Eighty-three mothers of affected children were interviewed. The results showed that 43% of parents were consanguineous, that 19% had a positive family history and that the frequency of coloboma was highest in second-born children. Eleven (16%) mothers had a history of night blindness while pregnant with the affected child; seven (8%) took medication during the 1st trimester, abortifacients in two cases; three reported fever in the 1st trimester; and 11 (13%) reported exposure to agricultural chemicals.

An essential role for frizzled 5 in mammalian ocular development

“…Among the siblings of affected individuals, the incidence of coloboma is ~100-fold higher than in the general population (Morrison et al, 2002), and it is also more common among progeny of consanguineous unions (Hornby et al, 2003). Additionally, vitamin A deficiency during gestation has been implicated as an environmental risk factor for coloboma (Seeliger et al, 1999;Hornby et al, 2002), consistent with the effect of vitamin A deficiency in rats and with the phenotypes of mice with targeted disruptions in genes involved in retinoic acid signaling.…”

Ocular coloboma: a reassessment in the age of molecular neuroscience

“…43 44 Most recently, a study showed that 16% of pregnant women from South India who gave birth to a child affected with coloboma, had suffered night-blindness that reverted after birth. 44 Evidence in support of a role for VAD is that 50% of pregnant women in parts of South India were found to have mild-to-moderate VAD. 44 However, due to the high frequency of consanguineous marriage in India, it has also been hypothesised that perhaps there is a genetic predisposition to the effects of VAD, leading to a higher prevalence of coloboma.…”

“…44 Evidence in support of a role for VAD is that 50% of pregnant women in parts of South India were found to have mild-to-moderate VAD. 44 However, due to the high frequency of consanguineous marriage in India, it has also been hypothesised that perhaps there is a genetic predisposition to the effects of VAD, leading to a higher prevalence of coloboma. 45 In more westernised countries, however, it seems unlikely that dietary VAD would occur.…”

A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in nine individuals from an inbred Muslim kindred

“…1,2 Both genetic and environmental factors, such as fetal alcohol syndrome and vitamin A excess or deficiency, contribute to congenital eye defects. [3][4][5][6][7] All types of Mendelian inheritance have been reported for A/M. The majority of genes known to be involved in the pathogenesis of A/M are transcription factors or homeobox genes.…”