http://www.docguide.com/news/content.nsf/news/8525697700573E1885256B100043BF9C
11/27/2001
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
Copyright (c) 1995-2001 Doctor's
Guide Publishing Limited
Journal of Neurology, Neurosurgery,
& Psychiatry (JNNP Online)
By Harvey McConnell