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