Posterior ocular malformations in children : teratological aspects

Posterior ocular malformations are common causes of visual impairment in Swedish children. The most frequent diagnoses within this group are optic nerve hypoplasia and optic nerve/chorioretinal coloboma. Genetic factors, teratogens like medical/addictive drugs or congenital infections and unknown factors may cause these malformations. The general aims of this work were to study the impact of various teratogens on ocular structures and visual function in children and to evaluate associated somatic disorders in children with posterior ocular malformations. Paper I describes 43 children exposed to anti-epileptic drugs during pregnancy, compared to 47 control children. Children exposed to low amounts of single therapy anti-epileptic drugs (predominately phenytoin or carbamazepine), where the mothers were carefully monitored during pregnancy did not develop severe ocular malformations. Papers II-IV are based on Swedish data from a prospective European multi-centre study on infections with Toxoplasma gondii. Among 40 978 newborn children screened neonatally, three had congenital toxoplasmosis. Two were asymptomatic at birth and would have escaped early detection and therapy without neonatal screening. They were treated for 12 months with anti-parasitic therapy. Seroprevalence in adults, incidence of primary infection during pregnancy with Toxoplasma gondii and prevalence of congenital toxoplasmosis were low in Sweden. In Papers V and VI, 40 visually impaired children with posterior ocular malformations from the whole of Sweden, referred to Tomteboda Resource Centre were assessed on a multi-disciplinary basis. Children with optic nerve hypoplasia more often had severe visual impairment, were diagnosed later and suffered to a greater extent from neonatal and endocrinological insufficiencies than children with coloboma/microphthalmus. Neuroradiologically, an abnormal pituitary region indicated endocrinological insufficiencies. Neonatal hypoglycaemia predicted for neurological, endocrinological and/or cognitive dysfunction. Exposure to Vitamin A, alcohol or anti-depressive drugs was found in five children. Dried blood spot cards, collected for routine metabolic screening, were retrospectively analysed with polymerase chain reaction to detect congenital cytomegalo- or herpes simplex virus infection. Herpes simplex virus type 1 DNA was identified in one child with optic nerve hypoplasia whereas cytomegalovirus DNA was not found in any child. In Paper VII, four children with hepatic disease presenting as neonatal cholestasis and visual impairment due to optic nerve hypoplasia are described. Common aetiological mechanisms are discussed and it is suggested that endocrine insufficiencies and cholestasis occur in variable clinical combinations in infants with optic nerve hypoplasia. In conclusion a multi-disciplinary approach is of great importance in children with posterior ocular malformations in order to accurately describe associated endocrinological insufficiencies, CNS abnormalities, neurological or neuro-psychiatric dysfunction and, with reference to young infants, accompanying cholestasis. Further evaluation is needed of the role of congenital infections and anti-depressive drugs and their association to posterior ocular malformations