ABSTRACT

X-linked juvenile retinoschisis (XLRS) is a disease considered characteristic for males. In this study we report a consanguineous family in which 3 daughters were diagnosed with XLRS. Typical signs of XLRS were detected in 2 girls, aged 4 and 15. Fundoscopic examination of the father and the oldest daughter (age 17) revealed bilateral atrophic macula and retinal thinning. Although rare and considered characteristic for males, XLRS can be seen in females in Middle-East countries that have a high rate of consanguineous marriage. It can be overlooked by ophthalmologists and these patients may be misdiagnosed.

Introduction

Although X-linked retinoschisis (XLRS) is reported as rare in the literature, XLRS is the most common cause of juvenile macular degeneration.^1,2 Diagnosis can be established through a fundus examination and optical coherence tomography (OCT), but electroretinography (ERG) is required for a definitive diagnosis.^1,3,4

In this study we present the findings of a family with consanguineous marriage from the Central Anatolia region of Turkey in which the father and 3 daughters were affected by XLRS. The family consisted of the father and 3 daughters with XLRS, and the mother and another daughter who had normal ocular examination findings. The diagnosis of this rare disease is quite difficult even in the typical male patients and we want to emphasize the rare possibility of XLRS in female patients, especially in countries with high frequency of consanguineous marriage.

Discussion

XLRS has been reported in a limited number of studies in female children, particularly of consanguineous parents.^1,5,6 In our study, we report a family with consanguineous marriage from Turkey in which the father and oldest daughter (age 17) had macular atrophy and 2 other daughters (age 4 and 15) had active foveal retinoschisis with no peripheral retinoschisis, which had been misdiagnosed as idiopathic macular edema. Although foveal retinoschisis is detected in almost all patients, schisis and cystic changes disappear in some patients in adulthood, and a nonspecific macular appearance develops. This nonspecific appearance might hinder accurate diagnosis.⁷ Researchers in the literature generally reported atrophy in individuals over the age of 30 years; however, we detected macular atrophy in the father, aged 42, and the 17-year-old daughter, and both showed retinal thinning in the foveal area on OCT.

The appearance of foveomacular retinoschisis may be confused with CME. However, FFA of patients with retinoschisis is often normal, or a slightly hyperfluorescent circular zone is observed in the edges of the macular area.⁸ The first member of the family was a 15-year-old daughter referred to our clinic with the diagnosis of CME. We detected no leakage suggesting CME on FFA of this patient, and we were unable to perform FFA in the 4-year-old daughter with retinoschisis. Goldmann-Favre syndrome, which is characterized by foveal schisis, is also important in the differential diagnosis. Autosomal recessive transmission, severe nyctalopia, pigmentary retinopathy, and attenuation of a- and b-waves in ERG are important for differentiation from XLRS.²

Study Limitations

One of the limitations of our case was that we could not draw a family tree due to missing data about the ocular condition of the families of the mother and father. Another limitation was that we did not conduct molecular gene analysis, which could have contributed to the literature. Such a workup would certainly have yielded very precious information regarding the possibility of meaningful genotype-phenotype correlations in X-linked juvenile retinoschisis.

In conclusion, XLRS, which manifests with low vision in the first decade of life, is detected at a high frequency in countries with high prevalence of consanguineous marriage, and the importance of genetic counseling is growing in these countries. Taking this rare condition into consideration will prevent incorrect treatment for CME in these patients. These patients may be treated for misdiagnoses such as amblyopia, strabismus, hyperopia, and astigmatism. The correct diagnosis can prevent the application of inappropriate treatments, and informing the patients about the risk factors for development of retinal detachment and taking precautions may prevent the occurrence of complications like retinal detachment. In addition, early diagnosis of individuals with XLRS will become more important because RS1 (retinoschisis 1) gene therapy outcomes in animal models are promising.

Çalışmanın Kısıtlılıkları

Çalışmamızın kısıtlılıklarından biri anne ve babanın ailelerinde görülen göz hastalıkları ile ilgili verilerin tam olarak elde edilememesi nedeniyle aile ağacının çizilememiş olmasıdır. Bir diğer kısıtlılık ise literatüre katkı sağlayabilecek moleküler gen analizi yapmamamızdı. Böyle bir analiz kesinlikle, X’e bağlı juvenil retinoskizis için genotip-fenotip korelasyonlarının olasılıkları hakkında çok değerli bilgiler sağlayabilirdi.

Sonuç olarak, yaşamın ilk on yılında az görme ile kendini gösteren XLRS, akraba evliliği prevalansı yüksek olan ülkelerde sıklıkla tespit edilmekte ve bu ülkelerde genetik danışmanlığın önemi artmaktadır. Nadir görülen bu hastalığın akılda bulundurulması, bu hastaların KMÖ tanısı konularak yanlış tedavi edilmesini önleyecektir. Bu hastalar ayrıca ambliyopi, şaşılık, hipermetropi ve astigmatizma gibi yanlış tanılar ile de tedavi edilebilmektedir. Doğru tanı hatalı tedavileri önleyebilir ve hastaların retina dekolmanı gelişimi için risk faktörleri hakkında bilgilendirilmesini ve önlem alınmasını sağlayarak retina dekolmanı gibi komplikasyonların ortaya çıkması engellenebilir. Ayrıca hayvan modellerinde RS1 (retinoskizis 1) gen tedavisi sonuçları umut verici olduğundan XLRS hastalarının erken tanısı daha önemli hale gelecektir.