Electrophysiology in visually impaired children

Abstract

Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates its value in establishing diagnoses and predicting the course of a disease, with consequences for the rehabilitation process. The electrophysiological results also contribute to the understanding of pathophysiological mechanisms and sometimes lead to new hypotheses. Chapter 2 describes the results of a retrospective study of 340 electro-ophthalmological investigations in children, performed without sedation or anaesthesia. The children had a mean age of 7 ± 5 years; only 4% of the examinations failed because of lack of compliance. The most frequently established disorders were tapetoretinal dystrophy, congenital stationary night blindness, and cone dystrophy. In 26 children (9%) a previously established diagnosis was changed; in 20 of them leading to a change of prognosis. These diagnostic changes profoundly influenced the rehabilitation process. Chapter 3 reports on a 15-year-old girl with a multi-system disorder. The electro-ophthalmological findings combined with the systemic features led to the diagnosis of thiamine responsive megaloblastic anemia syndrome (TRMA). Because of this diagnosis the girl was treated with thiamine, which resulted in normalization of her blood cell count and hemoglobin concentration without further need for blood transfusions. Chapter 4 describes the ocular and electrophysiological findings in 24 patients with Rubinstein-Taybi syndrome. 78% of the 24 investigated patients proved to have a retinal dysfunction; this high frequency had not been described before. Four patients had normal ERGs and VEPs, indicating phenotypic, and possibly also genetic, heterogeneity. In Chapter 5 reports on the clinical and ophthalmological characteristics of two siblings with ectrodactyly, ectodermal dysplasia, and macular dystrophy (EEM syndrome). Fundus appearance and ERGs pointed to a congenital retinal abnormality, possibly associated with Bruch's membrane pathology, rather than a progressive condition. EEM is caused by mutations in CDH3, encoding P-cadherin; mutations in this gene are also responsible for hypotrichosis with juvenile macular dystrophy (HJMD). The results suggested that EEM and HJMD may represent phenotypic heterogeneity of the same syndrome. In Chapter 6 three non-albinotic patients are described with misrouting and foveal hypoplasia. Misrouting is considered to be the hallmark of albinism, and foveal hypoplasia an important ocular feature of the condition. However, the findings in this study indicated that pigmentation is not the only decisive factor in determining misrouting and foveal hypoplasia. Misrouting in these patients may have been caused by defective genes involved in chiasm development. Furthermore, we propose the hypothesis of misrouting exerting a retrograde influence on foveal development. In Chapter 7 the characteristics of autosomal recessive congenital stationary night blindness (arCSNB) are described. Mutation analysis in five of the seven patients showed mutations in GRM6. The patients with mutations showed unusual ERG results when measured with 15 Hz scotopic flicker stimulation; these measurements may therefore be used in the diagnosis of arCSNB. The electrophysiological results indicated the existence of alternative pathways for rod signalling under scotopic conditions.