X-linked Juvenile Retinoschisis Author: Doctor Bernard PUECH1 Creation Date: March 2003 Update: May 2004 Scientific Editor: Professor Jean-Jacques de Laey 1Exploration Fonctionnelle De La Vision, Hôpital Roger Salengro, 59037 Lille, France. [email protected] Abstract Keywords Diagnostic criteria/definition Synonyms Historical overview Excluded diseases Differential diagnosis Prevalence Clinical description Evolution Treatment Etiology Diagnostic methods Genetics Genetic counseling Prenatal diagnosis References Abstract X-linked retinoschisis is a congenital ocular disease secondary to an abnormal cleavage of the innermost layer of the retina. The frequency has been estimated at 1/28 000 in the North of France and 1/17 000 in Finland. This ocular disorder is characterized by a bilateral cystic macular lesion at the level of the posterior pole of the retina and, in more than one third of the cases, by a bullous elevation of the peripheral retina. This peripheral elevation or schisis can be associated with veils and preretinal vitreous condensations. The lesions are present at birth or appear during the first years of life. They have little tendency to progress. Whereas the peripheral lesions will eventually flatten and even disappear with time, the central lesion progresses towards atrophy. Vision slowly decreases with age, resulting in poor central vision after the fifth decade. No treatment is needed in the simple form. However, surgery should be considered in the presence of major complications, such as severe vitreoretinal traction resulting in haemorrhages, retinal tears or rhegmatogenous retinal detachment. This condition is inherited as a recessive X-linked trait. The gene has been localized (Xp22.2-p22.1) and numerous mutations have been identified. The physiopathology remains to be elucidated. Keywords Cataract; congenital peripheral schisis; discoïdine; foveolar cysts; hypermetropia; nystagmus; retinoschisin; rhegmatogenous retinal detachment; schisis; stellar shaped macula; strabismus; vitreoretinal veils; X-linked macular disease Diagnostic criteria/definition peripheral retinal and vitreous lesions. The X-linked retinoschisis is a bilateral retinal retinal lesions are probably already present at disease with a recessive X-linked mode of birth or appear during the first months of life. The inheritance, characterized by a maculopathy maculopathy consists of bilateral star-shaped which is present in all cases and is associated in microcystic macular changes. The retinal somewhat less than 50% of the cases with periphery is only involved in about 40% of cases, Puech B. X-linked Juvenile Retinoschisis. Orphanet Encyclopedia. May 2004. http://www.orpha.net/data/patho/GB/uk-XLRS.pdf 1 and then presents an inferotemporal schisis, examination revealing poor vision, strabismus or vitreous veils and condensations and, more tractional retinal complications. Distant visual rarely, vitreoretinal membranes. acuity may vary between 2 and 7/10, near vision being usually better. Hypermetropia, strabismus Synonyms and nystagmus have been classically described • X-linked congenital retinoschisis but are not necessarily present. • Hereditary juvenile retinoschisis The central retinal lesion consists of fine radial • X-linked juvenile retinoschisis folds of the inner limiting membrane covering the • Cystic retinal disease in children macula and centered on the foveola. This • X-linked vitreoretinal degeneration configuration is stellar or “wheel-like”. It is • XLRS particularly obvious with the scanner laser • RS ophthalmoscope (SLO). In the center of this stellar lesion, at the foveola, the striations are Historical overview prolonged by small round and reddish In 1898, Haas was the first to describe the microcysts. In 98% of younger patients, this ophthalmoscopic appearance of what he called central lesion is present in a more or less cysts in "wheel spokes". The familial nature of obvious fashion. the disease was recognized by Pagenstecher in A peripheral retinoschisis is observed in 1913 and several authors described the somewhat less than half of the cases. It projects condition under different names. In 1935, into the vitreous as a semitransparent bullous Wilczek introduced the term retinoschisis detachment, most often localized in the (schisis -> cleavage). inferotemporal quadrant. This detachment is sometimes limited to one or more Excluded diseases semitranslucent vitreous veils, which contain Dominant or autosomal recessive foveolar retinal vessels. The peripheral retinoschisis may retinoschisis be variable in size. In the most severe forms, it Goldman-Favre syndrome may reach and involve the macula, it may also Peripheral vitreoretinal degeneration look like a vitreoretinal traction fold between the Senile peripheral retinoschisis retinal periphery up to the optic disc. In female carriers, clinical signs signs have been Differential diagnosis described, such as loss of foveal reflex, hardly The macular lesion can be mistaken for visible folds of the internal limiting membrane or sequelae of cystoid macular oedema (CMO), irregular macular pigmentation, and were which can occur bilaterally in case of autosomal considered as "Lyonisation" phenomena. dominant CMO or as a complication of retinitis However the foveal reflex disappears in the adult pigmentosa or allied diseases. An around the age of 35 years, which corresponds electronegative ERG can be found in congenital to the mean age of mothers of affected children hemeralopia. The peripheral lesions may be at diagnosis. Macular pigment irregularities can reminiscent of those seen in Goldman-Favre be observed in otherwise normal individuals over disease. There are some similarities between the age of 40 and the subtle macular folds have the peripheral fundus lesions of X-linked only been exceptionally noticed in female retinoschisis and those of retinopathy of carriers. According to Kaplan (1991), female prematurity (ROP). Autosomal dominant as well carriers frequently present with discrete as autosomal recessive macular retinoschisis peripheral retinal lesions similar to those seen in have been described and should be considered affected adult males. in the differential diagnosis of X-linked The visual field shows a relative central scotoma retinoschisis with isolated macular lesions. and sometimes major peripheral constriction when the peripheral schisis is important. Prevalence The color vision is only mildly affected. The prevalence has been estimated at 1/28 000 The electroretinogram is always affected and is in the North of France (Puech 1991) and at electronegative. The photopic a-wave is larger 1/17 000 in Finland (de la Chapelle et al, 1994 ). than normal, especially in the beginning, and the b1-wave is small and negative; the scotopic b2- Clinical description wave is also negative and markedly modified or The diagnosis is seldom made in newborn even absent. It is noteworthy that Arden babies, except when the disease is very described in 1988 a rather complicated disabling resulting in nystagmus and strabismus. electrophysiological technique, which could If other family members are affected, the diagnose female carriers. The electro-oculogram diagnosis can be made at an early age by the (EOG) is normal in 50% of cases and is systematic examination of newborns. The markedly affected only at older age. The visual diagnosis is most commonly made in early evoked potentials (VEP) are normal if the visual childhood, at the occasion of a school acuity is better than 2/10. Puech B. X-linked Juvenile Retinoschisis. Orphanet Encyclopedia. May 2004. http://www.orpha.net/data/patho/GB/uk-XLRS.pdf 2 Fluorescein angiography does not generally Etiology show changes in children, except discrete Histologically, it has been demonstrated that the fluorescence at the level of the foveola. In lesions of juvenile retinoschisis are secondary to advanced forms, in adults, perimacular annular an abnormal cleavage of the retina at the level of window defects are sometimes seen. its innermost layer, the nerve fiber layer (Yanoff 1968, Manschot 1972). This led to the Evolution hypothesis that the lesions resulting from After the age of 40 years, the macular schisis cleavage are malformative in nature and becomes less obvious and is replaced by a congenital, especially as they could be detected macular atrophy with pepper and salt in the newborn (Sauer 1997). In the light of this appearance and a prognosis similar to that of hypothesis, the disease would not progress atrophic age-related macular degeneration. The further after birth, but tissues would be damaged peripheral schisis initially also progresses quite by the initial malformations and degenerate. slowly. Classically, worsening occurs up to the Epidemiological studies on the fertility of female age of 20 years, and is characterized by the carriers and the sex ratio (see “Genetics” ) seem extension of the surface of the schisis. Later, also to support this hypothesis. There could be a spontaneous reapplication may occur; the pleiotropic action of the gene defective in schisis fades whereas gradually expanding holes retinoschisis, XLRS1, affecting embryonic are formed in its wall. The periphery takes the implantation and survival (Huopaniemi 1999). aspect of an atypical atrophic degeneration with Immunohistochemistry however is not in favor of sometimes spotted areas with brownish or a pure malformation disorder, as it detects the miccalike reflexes. Sheathed and occluded gene product, the secreted retinoschisin, in the retinal vessels