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Br J Ophthalmol. 2007 July; 91(7): 983–984.
PMCID: PMC1955645

Exudative retinopathy in a girl with alström syndrome due to a novel mutation

Coats disease is an uncommon telangiectatic retinal exudation that is most often seen in males. Similar changes are an uncommon but well known complication of retinitis pigmentosa, occurring in up to 3.6% of the affected individuals.1 This association has not been reported with Alström syndrome. Alström syndrome is a rare autosomal recessive disorder caused by mutations in a novel gene of unknown function, ALMS1,2 widely expressed in centrosomes and the base of cilia.3,4 We report an Asian girl with bilateral congenital cone‐rod dystrophy due to Alström Syndrome who developed subretinal exudation resembling Coats disease.

Case report

A twelve year old girl of ethnic Pakistani origin presented with marked deterioration of vision in her right eye over the previous year. She had attended our institution with cone‐rod retinal dystrophy (ERG demonstrated absent photopic response & markedly reduced rod response), infantile‐onset obesity, cardiomyopathy, sensorineural deafness, diabetes mellitus with hyperinsulinaemia, hepatosplenomegaly and recurrent urinary tract infections for several years. There was no history of polydactyly. On this basis, a clinical diagnosis of Alström syndrome was made.

On examination, there was no demonstrable vision in the right eye and only bare perception of light in the left. Slit‐lamp examination revealed quiet anterior chambers without evidence of rubeosis in either eye. A right exotropia on penlight examination with manifest horizontal pendular nystagmus was noted. Fundal examination (fig 11)) of the right eye revealed severe submacular lipid exudation with an inferior exudative retinal detachment involving the macula. The left eye had a waxy disc, some midperipheral subretinal flecks, a characteristic macular sheen and no visible subretinal exudation. Fundus fluorescein angiogram showed massive capillary dropout and mid‐peripheral neovascularisation in the right eye. The left eye only showed hyperfluorescence from subretinal flecks. There was no angiographic evidence of retinal ischemia in this eye. Based on this, a clinical diagnosis of exudative retinopathy in the right eye was made. Management was difficult in view of the poor visual acuity in the right eye with such a dramatic exudative retinal detachment. After discussing treatment options with the parents, they opted for retinal cryotherapy to prevent the development of a painful, rubeotic eye.

figure bj88781.f1
Figure 1 Fundus photograph of the right eye showing exudative retinal detachment involving the macula.

The patient was the second child of first cousin parents. She had a cousin and two siblings similarly affected. They had a similar phenotype with cardiac failure in infancy, early deafness, retinal dystrophy and diabetes mellitus. Molecular analysis confirmed linkage to the Alström locus on chromosome 2p13. Mutation analysis identified a 1444 nucleotide deletion (IVS8 + 895 del 1444) encompassing the whole of exon 9 of the ALMS1 gene. This is a novel mutation for Alström syndrome, identified in this single family and has recently been reported by our institution.5

Comment

Alström syndrome is a rare autosomal recessive disorder caused by mutations in the novel gene ALMS12 which has been shown to be widely expressed and localised to centrosomes and the base of cilia.3,4

A review of ocular features in Alström Syndrome reported poor visual acuity in the order of 20/200 or worse by 10 years.6 Unlike other retinal dystrophies, this condition can result in vision as poor as perception of light by the end of the second decade. However exudative retinopathy has not been documented in any of the above 22 cases in this series.

Nonetheless, exudative retinopathy has been demonstrated uncommonly in longstanding retinitis pigmentosa. Mutations in the crumbs homologue 1 (CRB1) gene are strongly associated with the development of Coats‐like exudative vasculopathy in these patients.7 This entity differs from classic Coats disease in terms of relatively higher incidence of bilateral involvement in exudative retinopathy, equal gender incidence, mode of inheritance and location of retinal pathology.1 We are reporting a unique mutation associated with a novel phenotype in our patient in the Alström locus. As this is a single case, we cannot be certain that the retinal exudation is definitely caused by this mutation.

Our patient however had unilateral exudative retinopathy. This may be due to an asymmetry of the retinal dystrophy between the eyes. The natural history of this retinopathy is unknown and the beneficial results of treatment varying from photocoagulation,8 cryotherapy9 and pars plana vitrectomy10 are difficult to quantify.

It is possible that in time, the other eye may become affected, probably as the retinal dystrophic changes progress.

References

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8. Koshibu A, Uyama A, Matoba H. et al Two cases of retinitis pigmentosa associated with retinal vasculopathy. Jpn J Clin Ophthalmol 1979. 331523–1532.1532
9. Yuguchi M, Majima A. A case of retinitis pigmentosa associated with Coats syndrome. Ophthalmol Pediatr Genetics 1984. 4177–182.182
10. Lee S Y, Yoon Y H. Pars Plana Vitrectomy for exudative retinal detachment in Coats type retinitis Pigmentosa. Retina 2004. 24450–452.452 [PubMed]

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