Despite being the most common inherited cause of intellectual disability, fragile X syndrome is a condition that most patients I meet with have never heard of before. Fragile X syndrome is far from rare. About 1 in 6,000 babies is born with the condition. Most do not show symptoms though, for a year or two. Around this age, toddlers often start to fall behind their peers in their development. On average, boys with fragile X syndrome sit unsupported at 10 months and walk and speak their first clear words around 20 months, several months later than is typical.
Other health problems are common as well. Over 80% of boys with fragile X syndrome have an attention deficit and around 70% have anxiety. In addition to being a common cause of intellectual disability, fragile X syndrome is also the most common single-gene cause of autism. Over 40% of boys with fragile X syndrome have autism. Because of this, current medical guidelines suggest that anyone with a diagnosis of autism should have genetic testing for fragile X.
While an inherited condition, fragile X syndrome is tricky because most babies at risk have no family history of the condition. A woman can unknowingly carry a genetic change that increases risk for fragile X syndrome in her children even if she has no signs of the condition herself.
Because of this, genetic testing for fragile X syndrome is not just offered to children with intellectual disabilities and autism. Screening is also routinely offered to all women who are pregnant or planning a pregnancy. For most, the results of this testing provide reassurance that the chance for fragile X syndrome is low. For others, knowing of the increased risk helps with planning and reproductive decision-making.
There is currently no specific treatment for fragile X syndrome apart from supportive care such as special education and medications to treat individual symptoms. Changes may be on the horizon though.
A study published earlier this year in Clinical Genetics reported on seven people with fragile X syndrome who were treated with the drug metformin. Metformin is an oral medication typically used to control blood sugar levels in people with diabetes or obesity. In these seven cases, metformin not only improved blood sugar control, but also some symptoms of fragile X syndrome. The study found improvement in levels of irritability, social unresponsiveness, hyperactivity, and social avoidance. Improved language skills were also reported by the treated individuals’ family members.
An additional study from Nature Medicine last month found mice with fragile X syndrome to have improved social skills and less seizures after treatment with metformin. Similar findings have been reported previously in other animal models of fragile X syndrome.
Clinical trials in humans are needed before using metformin to treat patients with fragile X syndrome. However, it is encouraging that metformin already has a proven track record of being a safe drug that is tolerated well. If these trials are able to successfully show improvement in the core symptoms of fragile X syndrome, metformin may become a new, targeted treatment for this not-so-rare disease.
July is fragile X syndrome awareness month. To learn more about fragile X syndrome, visit the National Fragile X Foundation. For genetic testing for you or a family member, contact a Certified Genetic Counselor in your area.