AAN: Pediatric-onset MS – environmental and genetic risk factors

Between 2 – 5% of multiple sclerosis cases emerge before the age of 18. Research into MS in children and adolescents – referred to as pediatric-onset MS – is not only important for managing the disease in youth, but can also provide insights into some of the earliest triggers and drivers of MS, with implications for understanding and treating MS across all groups. Since MS is believed to spring from a combination of specific genetic and environmental factors, invited speakers at the pediatric-onset MS seminar session presented new data exploring these factors in children and adolescents.

Credits: American Academy of Neurology

Credits: American Academy of Neurology

To open, Dr. Lisa Barcellos (University of California, Berkeley, USA) presented data from the first genome-wide association study (GWAS) conducted in pediatric-onset MS. GWAS is a powerful technique incorporating sophisticated genetic and statistical methods that can identify specific genetic variants (different forms, or alleles, of the same gene) and link them to specific disease outcomes. Dr. Barcellos’ team gathered whole genome profiles from 732 youth living with MS and 27,197 healthy controls. When they did a subgroup analysis of the Causasian participants, they found that many, although not all, of the same gene variants associated with MS in adults were also linked to an increased risk of MS in youth. In fact, some gene variants had an even stronger linkage with MS in pediatric-onset cases than in adults. Further research is underway to map out genetic risk factors among racially-diverse populations, and to determine if there is a casual relationship between some of these gene variations and MS risk in youth.

Dr. Tanuja Chitnis (Brigham and Women’s Hospital, USA) presented research that examined whether puberty and obesity can influence the risk of developing pediatric-onset MS as well as the age of MS onset. Her team conducted a case-control study of 254 children and adolescents with MS and 420 healthy controls. Obesity was quantified using body mass index (BMI), and sexual maturity was determined using measurements of various sex hormones and development of primary and secondary sexual characteristics. They found that boys with a higher BMI had an overall greater risk of developing MS; this relationship was also found in girls after the onset of puberty. In boys in particular, earlier age of sexual maturity was associated with an earlier age of onset of MS symptoms. The information gained from this study can help identify children who are at higher risk of pediatric-onset MS and shape strategies designed to manage certain risk factors like childhood obesity.

One question that I often hear from pregnant women is, “what kinds of environmental exposures during pregnancy can increase the risk of MS in my child?” Dr. Jennifer Graves (University of California San Francisco) presented data from a case control study of children with either MS or clinically isolated syndrome (CIS) to determine if maternal exposure to certain environmental factors before, during or soon after pregnancy can modify MS risk in children. Using questionnaires from 275 mothers of children with MS/CIS and 437 mothers of children without MS, Dr. Graves found several pregnancy-related factors that were linked to a higher risk of pediatric-onset MS. Among these were maternal illness during pregnancy, which was associated with a 2.3-fold increase in the odds of the child developing pediatric-onset MS. One surprising finding was that overall exposure to plant-related pesticides conferred a higher risk of MS to the child; methods of exposure included the use of household plant pesticides, or having a father who worked in a gardening- or farming-related job. Dr. Graves indicated that these findings are still preliminary and will need to be verified in more thorough follow-up studies.

Another common question is whether diet has any effect on MS risk in children in adolescents. Dr. Julia Pakpoor (University of Oxford) explored this question in 260 kids with MS and 393 controls, and with the use of self-reported questionnaires measured dietary intakes of various nutrients, including fats, proteins, carbohydrates, sugars, fruits & vegetables, iron, fiber, etc. Dr. Pakpoor found that overall, only low iron intake appeared to be significantly associated with an increased risk of MS, suggesting that dietary iron intake may have a potential protective influence on the risk of developing pediatric-onset MS.

One nutrient in particular – vitamin D – was the focus of the next study, presented again by Dr. Barcellos. Using a genetic technique called Mendelian Randomization, Dr. Barcellos and her colleagues set out to determine if higher vitamin D levels in the blood confer a protective effect against the risk of MS in children, as has been previously shown in adults (read the MS Update about this study). In her analysis of 394 MS cases and 10,875 controls, she found that higher blood vitamin D levels were associated with a reduced risk of MS in youth. These findings underscore the importance of maintaining sufficient blood levels of vitamin D in children as in adults, and will inform the development of specific guidelines for achieving minimum target levels of vitamin D to reduce the risk of MS in the population.

Finally, MS Society-funded researcher Dr. Helen Tremlett (University of British Columbia) presented data from a pilot study examining the association between the diversity of bacteria living in the gut (known as the gut microbiome) and the presence of certain immune system markers in the blood in children. By studying a sample of 15 children living with MS and 9 healthy controls at a single clinic, Dr. Tremlett found that a greater bacterial diversity of the gut microbiome was associated with greater levels of pro-inflammatory Th-17 immune cells in children living with MS, but not in healthy controls. These findings will be expanded and studied in greater detail in Dr. Tremlett’s MS Scientific Research Foundation-funded study of the gut microbiome in collaboration with the Canadian Pediatric Demyelinating Disease Study led by Dr. Brenda Banwell (Children’s Hospital of Philadelphia).

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