Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals

A genetic basis for clustering of multiple sclerosis (MS) cases, based on s tudies of MS families, has been Proposed for decades. Few reports provide d etailed neurological as well as neuroradiological findings on these patient s. We report total T2-weighted intracranial lesion volumes on members of th ree familial MS cohorts: a mother and father with conjugal MS with one affe cted son and a neurologically normal son and daughter, one pair of monozygo tic twin sisters with MS, and a female sibling pair with MS. We hypothesize d that asymptomatic siblings in a family with two affected parents and anot her affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS ore more likely to express similar T2-w eighted lesion volumes than non-twin sibling pairs. We found clinically sil ent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total Tw lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and signif icantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parent s with MS, possibly reflecting a genetic predisposition to subsequent devel opment of MS.