Men with Multiple Sclerosis Pass Disease to Offspring More Often than Women

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According to a new study, men transmit multiple sclerosis (MS) to their children 2.2 times more often than women in families where the father or mother and a child have multiple sclerosis.

This study involved an investigation of 444 children of an MS-affected father or mother from 3,598 individuals in 206 families to compare the transmission of MS between affected men and women. The findings by researchers from Mayo Clinic, the University of California at San Francisco, the University of California at Berkeley and Kaiser Permanente will be published in the July 25 issue of the journal Neurology.

“Fathers with MS tend to have more children who develop MS than do mothers with the disease,” says Brian Weinshenker, M.D., Mayo Clinic neurologist and study investigator. “When we looked at a large population of MS patients, when there was a parent and a child who had MS in a family, the child with MS got the disease twice as often from the father rather than the mother.”

MS affects approximately 1 in 1,000 people, and it is twice as common in women as in men. In 85 percent of cases, no cause is known. For 15 percent of MS patients, a family member within a generation also is affected by the disease. For familial cases, no single gene has been identified that strongly predisposes a person to MS.

“Rather, a combination of genes and unknown environmental factors work together to cause multiple sclerosis,” says Orhun Kantarci, M.D., Mayo Clinic neurologist and lead author of the paper.

The researchers theorize that men may have a greater “genetic load” of MS genes, which may explain their findings.

“The hypothesis of the study is that men are more resistant to MS, so they need stronger or a larger number of genes in order to develop MS, and then pass these genes to their children,” says Dr. Kantarci.

He also explains that the overtransmission of MS by men in the study is not easily explained by hormonal differences between men and women or by genes on the sex chromosomes.

The findings shouldn’t change how men with MS are counseled about the risk to their offspring, say the researchers. The risk of having MS if a person has an affected parent is increased by about 20-fold compared to not having an affected parent; the additional risk by virtue of having an affected father is not sufficient to change patient counseling practices, says Dr. Kantarci.

“The overtransmission by men is primarily of interest to scientists studying the mechanisms of genetic transmission of MS susceptibility,” said Dr. Kantarci, “and may indicate that nontraditional, or so-called epigenetic factors, play some role in the transmission of MS.”

The investigators also indicate that their findings should be confirmed in another study by other researchers to be widely accepted.

No intervention prevents men from passing on MS, say the researchers, who indicate the necessity for MS researchers to identify the reason for this overtransmission by men, including finding genes predisposing to the “parent-of-origin” effect observed in this study.

Mayo Clinic

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