The first part of this study concerns the still little known clinical picture of choroideremia, while the second part deals with the rare affection known as gyrate atrophy of the choroid and retina. Both parts first present a review of the changes described by other authors and a discussion of the mode of inheritance of these hereditary eye diseases, followed by a report on a personal investigation of cases found in the Netherlands and a comparison of our findings with those of other authors. The nine pedigrees (including a large one combining four others) included 52 patients and 96 carriers; 45 patients and 61 carriers were examined by us. The first fundus changes seen in six patients, the youngest of whom was 1 1/2 years old, were fine granular pigment accumulations at the equator and periphery. They were localized deep in the retina at the level of the pigment epithelium. Not a trace of choroidal atrophy was seen in this initial stage. Subsequent stages showed fundus changes which are readily confused with those of other fundus affections such as gyrate atrophy of the choroid and retina on the one hand, and atypical tapetoretinal degeneration with choroidal sclerosis on the other. The 45 patients included 28 myopes, 12 emmetropes and four hypermetropes; in one, refraction was not determined. Emmetropia was mainly seen in the incipient cases. In 11 of the 13 patients in whom refraction was followed up, progression of the myopia was seen during the period of observation. Dark adaptation, visual fields, ERG and EOG were found normal in the initial stage. Unmistakable pathological changes occurred in these values in subsequent stages. The carriers showed widely varied fundus pictures, ranging from mildly abnormal pigmentation to features closely resembling the changes which characterize the choroideremia patient. Three carriers from three different pedigrees showed both the subjective and objective features normally found in patients. In addition to night blindness, these women showed fundus changes resembling those seen in patients in an advanced stage, and pathological changes in dark adaptation, visual fields, ERG and EOG. On the other hand, one carrier (daughter of a patient) showed no fundus changes at all. An exceptional fundus picture with the aspects of a tapetum-like reflex as described by Mann, was observed in one woman. It is not known whether she is a carrier or not. In three pedigrees the choroideremia occurred in association with another X-chromosomal eye affection (protanopia in two pedigrees, and deuteranopia in one). In all three pedigrees, crossing-over could be assumed as highly probable. To explain, on the one hand the complete clinical picture of a patient seen in three carriers, and on the other hand the complete absence of changes in one carrier, alterations in the expressivity of the pathological gene or possibly of the allele are suggested. In view of the fact that no trace of choroidal atrophy was seen in the initial stage, it seems probable that the primary seat of the affection lies in the pigment epithelium (tapetum nigrum). Consequently we accept Waardenburg's suggestion to change the designation choroideremia into progressive tapetochoroidal degeneration. The five pedigrees included 13 patients, 11 of whom were examined. The chief complaints were found to result from myopia and night blindness occurring early in life. Objectively, the initial stage of the affection was characterized by the presence of sharply defined, garland-shaped, peripherally localized areas of choroidal and retinal atrophy; in the later stages these spread in the direction of the posterior pole, and often connect with an annular peripapillary atrophic field. Myopia was found in 11 cases; it showed progression in a relatively large percentage of these cases. The choroidal and retinal atrophy showed a more central localization in one hypermetropic patient. Our findings also confirmed the high rate of complicated cataract in gyrate atrophy; this type of cataract was found in six of our 13 patients. The autosomal recessive inheritance of gyrate atrophy was confirmed by our findings. The consanguinity found in three of the five families is another argument in favour of this. Association of gyrate atrophy with complicated heterochromia (Fuchs) was observed in one female patient. Alder's anomaly was not demonstrable in the six patients examined for this purpose. Special attention has been given to the concomitance of tapetoretinal degeneration and gyrate atrophy of the choroid and retina, which a few authors have described, but which we were unable to confirm.
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