R 437
Genotype-phenotype-correlations: New demands to defining the phenotype
B. Lorenz
Precise phenotyping is essential for efficient genotype-phenotype correlation of retinal dystrophies as many genes have a clinically similar phenotype (locus heterogeneity) and mutations in the same gene may lead to different phenotypes (allelic heterogeneity). The aim of phenotyping is to document structural changes with high spatial resolution and to describe the pathophysiological processes with high precision. This is also a prerequisite for upcoming therapeutic trials.
Evaluation of structure: Biomicroscopy including fundus photography and angiographic methods are still of main importance. Newer methods include measuring autofluorescence that visualizes lipofuscin and lipofuscin like substances in their spatial distribution. Optical coherence tomography (OCT) allows in vivo sections through the retina.
Electrodiagnostics: Standards have been developed for EOG, Ganzfeld ERG, pattern ERG, and VEP by the International Society for Clinical Electrophysiology of Vision. In addition, a-wave analysis allows a more precise description of photoreceptor function. Using long stimuli allows to differentiate between pathologies of the on- and off-bipolar cells. Multifocal ERG allows mapping of the electroretinographic activity.
Psychophysics: Static and kinetic perimetry are performed in the light-adapted state and thus measure mainly cone function. Dark adapted two colour threshold perimetry discloses the relation of rod and cone dysfunction in spatial resolution. Dark adaptation curves describe the kinetics of cone and rod adaptation to dark.
Retinal dystrophies are not described sufficiently by a static image of the functional loss. Serial examinations over years are necessary. Also, the same gene defect does not necessarily imply the same clinical course as modifying genes and exogenic factors may influence the phenotype. Limitations of defining the phenotype come from still limited resolution of the methods, patients´compliance especially with respect to longitudinal studies, and high costs when larger numbers of patients need be investigated.
Department of Paediatric Ophthalmology, Strabismology, and Ophthalmo-genetics, Klinikum, University of Regensburg, D 93042 Regensburg