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Genetic Factors Influence Multiple Sclerosis Susceptibility

Genetic Factors Influence Multiple Sclerosis Susceptibility, Progression

A DGReview of :"Multiple sclerosis in sibling pairs: an analysis of 250 families"
Journal of Neurology, Neurosurgery, & Psychiatry (JNNP Online)

By Harvey McConnell

Genetic factors appear to determine susceptibility to multiple sclerosis and the way in which the disease progresses.

This emerges from a study of 262 pairs of siblings with multiple sclerosis (MS) from 250 affected families on the MS register carried out by Dr Alastair Compston and colleagues at the Neurology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, England.

The familial tendency of multiple sclerosis is well recognised with relative risks of 100-190 for identical twins; 7-13 for half and full siblings; and 5.5 for the offspring of single affected, and 60 for conjugal parents, Dr Compston and colleagues point out. Co-affected siblings can be used as a resource for identifying susceptibility genes and have formed the basis for genome screens in various diseases through linkage analysis including insulin dependent diabetes, asthma, and inflammatory bowel disease.

Using a cohort of 262 pairs of co-affected siblings from 250 families with multiple sclerosis, intersibling concordance analysis was used by the researchers to explore underlying genetic mechanisms in disease pathogenesis by assessing parameters of disease course, clinical presentation, age and year of onset, and measures of disability and handicap.

Dr Compston and colleagues found that only a third of sibling pairs (81/262), were concordant for presenting symptoms or the rate of relapse.

However, once the disease was established, the way in which the disease progressed was identical in 50 percent of the siblings. At the same time, objective measures of the extent and severity of disease, in terms of eventual handicap and disability, showed that these were also very alike.

The researchers conclude that their data and that from a recent French study when "taken together show that, within a sibship, the presentation is more likely to be different than the same. However, once established, concordance is more likely to be seen for the ultimate course, culminating in similar disability and handicap scores.

"As the disease process becomes established, measures of disease outcome are more likely than not to equilibrate within a sibship. Perhaps this is the expression of the hidden rounds of inflammation, demyelination, and axonal loss, which although initiated in different regions of the neuraxis, subsequently display similar tempos of progression and coalesce with the same outcome in any two siblings."

J Neurol Neurosurg Psychiatry 2001;71:757-761. "Multiple sclerosis in sibling pairs: an analysis of 250 families"

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