Ophthalmic Manifestations of the Alström Syndrome

Isabelle Russell-Eggitt; M.D, FRCS, FRCOph

Great Ormond Street Hospital for Children, London, UK

A diagnosis of Alström syndrome (AS) is made on the basis of phenotype and only recently has it been possible to confirm the diagnosis by detection of mutations in the ALMS1 gene. Therefore only individuals with typical features are recognised as the index case within a family. In some families there is more than one affected individual and there often is a variation in expression of some features which may be due to modifier genes. In large pedigrees the diagnosis is made earlier and is made in individuals who have not as yet developed all the typical features. This is how the infantile cardiomyopathy was recognised to be a feature of AS. In a sibling pair I have one child who had infantile cardiomyopathy and the other did not develop cardiac problems until the second decade. I have not seen this variability of expression or the retinal dystrophy either within or between sibships. In my personal experience all cases had severe vision handicap from birth. Dr Jan Marshall informs me that parents have reported vision problems as late as 2 year of age in mutation confirmed AS. In the majority of cases the retina is abnormal from birth. The photoreceptors are abnormal in structure and function with some residual function of rod receptors and the lack of development of foveal region. There is no treatment and vision progressively deteriorates to lack of light perception in the second decade. In the majority of cases there is useful vision early in life which is extremely helpful in early learning. Comfort and functional vision is optimised if dark glasses are with refractive correction are prescribed to utilise functioning rod receptors. There is no treatment for the retinal dystrophy as yet and AS is a multisystem disorder so treatment of a single organ will not alleviate all symptoms. Stage one human trials will soon be started in a retinal dystrophy of adult onset that is an isolated ocular disorder. As the ALMS1 gene has been identified in the distant future this gene therapy research may benefit AS patients.