More MS news articles for February 2001

Ask the Experts on . . .
Could Multiple Sclerosis Be an Inherited Disease?

http://neurology.medscape.com/Medscape/neurology/AskExperts/2001/01/NEUR-ae73.html

Question

I have a 28-year-old patient with relapsing-remitting multiple sclerosis for the past 3 years. Her mother is 42 years old and has had MS since age 20. This family includes 9 siblings: 5 sisters and 4 brothers. Two of the patient's sisters also have MS. One of them has optic neuritis, and MRI showed multiple brain lesions compatible with MS. The other sister has experienced 2 relapses with separate neurologic deficits, and her brain and cervical cord MRI showed multiple brain and cervical cord lesions compatible with MS. The parents are not relatives.

1. Does this family with MS present a true hereditary mode of transmission?

2. Do you recommend any specific gene study?

Thanks for your advice.

A.K. Daif, MD
Saudi Arabia

Response

from Rohit Bakshi, MD, 01/30/01

Multiple sclerosis (MS) is characterized by chronic inflammation, demyelination, and tissue loss in the central nervous system. Epidemiologic studies indicate that both genetic and environmental factors contribute to the etiology. Monozygotic (identical) twins have a 25% to 50% concordance rate for MS, whereas the rate is only 2% to 20% in dizygotic (fraternal) twins or other siblings. Because most monozygotic twins are discordant and, based on migrational, temporal, cluster, and epidemic studies, environmental factors are also important in the development of MS.

Approximately 15% to 20% of MS patients have a positive family history, and the presence of MS in a first-degree relative raises the risk of MS by 10- to 40-fold. People in the United States have a 0.1% chance of getting MS, whereas children of a patient with MS have a 1% to 4% chance of developing the disease. An MS patient has a 15% chance of having at least 1 affected relative. The highest risk is conferred to siblings, followed by parents, and then children. In agreement with this, most of the affected patients in the family that you describe are siblings. The 3 most important risk factors that increase a sibling's chances of developing MS are (1) female gender, (2) a parent with MS, and (3) MS onset in the index case in the second decade of life or earlier.

In the family that you describe, the presence of so many affected members is unusual and urges a careful exclusion of other causes (eg, familial spastic paraparesis, HTLV-1, hereditary arteriopathy, mitochondrial disease, etc.). If you have made a definitive diagnosis of MS in so many family members, it would support a hereditary mode of transmission in the presence of appropriate environmental factors. MS seems to be a complex trait in which susceptibility is determined by several genes. Much investigation has focused on the identification of the genetic markers of susceptibility to MS. The most consistent findings have been the association with the major histocompatibility complex (MHC) (also called human leukocyte antigen -- HLA) class II alleles, DR15, DQ6, Dw2, DR4, and DR2. Possible linkages with 6p21, 5p14, and 17q22 are also being studied. I do not recommend any specific blood test that would lead to definitive conclusions in this family, especially regarding therapeutic decisions. However, the family is of high interest for genetic MS research studies if these are available in your area of the world.

Suggested Reading

Compston A. The genetic epidemiology of multiple sclerosis. Philos Trans R Soc Lond B Biol Sci. 1999;354:1623-1634.

Compston A. The genetics of multiple sclerosis. J Neurovirol 2000;6(suppl 2):S5-S9

Ebers GC, Bulman DE, Sadovnick AD, et al. A population-based study of multiple sclerosis in twins. N Engl J Med. 1986;315:1638-1642 .

Ebers GC, Koopman WJ, Hader W, et al. The natural history of multiple sclerosis: a geographically based study: 8: familial multiple sclerosis. Brain. 2000;123(pt 3):641-649.

Fukazawa T, Sasaki H, Kikuchi S, Hamada T, Tashiro K. Genetics of multiple sclerosis. Biomed Pharmacother. 2000;54:103-106.

Kalman B, Lublin FD. The genetics of multiple sclerosis. A review. Biomed Pharmacother. 1999;53:358-370.

Rasmussen HB, Clausen J. Genetic risk factors in multiple sclerosis and approaches to their identification. J Neurovirol. 2000;6(suppl 2):S23-S27.

Sadovnick AD, Armstrong H, Rice GP, et al. A population-based study of multiple sclerosis in twins: update. Ann Neurol. 1993;33:281-285.

Sadovnick AD, Yee IM, Ebers GC, Risch NJ. Effect of age at onset and parental disease status on sibling risks for MS. Neurology. 1998;50:719-723.

Sadovnick AD, Dircks A, Ebers GC. Genetic counseling in multiple sclerosis: risks to sibs and children of affected individuals. Clin Genet. 1999;56:118-122.

Willer CJ, Ebers GC. Susceptibility to multiple sclerosis: interplay between genes and environment. Curr Opin Neurol. 2000;13:241-247.