In Focus

Seminar on Fragile X Syndrome

On September 29, 2023, at the Special Hospital for Cerebral Palsy and Developmental Neurology, a seminar on Early Recognition, Treatment, and Monitoring of Children with Fragile X syndrome was organized as part of the continuing education program. This seminar, labeled A–1–873/23, was accredited as a national course of the highest category, awarding 12 points to the lecturers and 6 points to the attendees. Led by professor Dragana Protić, DMSc, experts from our Hospital, who are also members of the team responsible for monitoring children with Fragile X syndrome, along with a guest lecturer, presented the latest advancements in the field researching Fragile X disorders.

Mutations in the FMR1 gene, located on the X chromosome, include an increased number of CGG triplets in this gene, which are classified as either incomplete mutations (premutations) or full mutations. An incomplete mutation of this gene is characterized by the presence of 55 – 200 CGG triplets within the FMR1 gene. The presence of more than 200 CGG triplets in the FMR1 gene is referred to as a full mutation. It is important to emphasize that the normal number of CGG repeats is always less than 45, and the range of 45 – 54 CGG triplets, known as the gray zone, has not yet been clinically clarified. The full mutation of the FMR1 gene (more than 200 CGG triplets) is clinically manifested as Fragile X syndrome. Fragile X syndrome is the most common cause of intellectual delays and autism resulting from a single gene mutation, and it occurs more frequently in boys.

Incomplete mutations of this gene are linked to two disorders: Fragile X Tremor Ataxia Syndrome (FXTAS), a neurodegenerative disease with similarities to Parkinsonism, which it is more common in men over the age of 50, and Fragile X Associated Primary Ovarian Insufficiency (FXPOI), characterized by premature ovarian insufficiency and premature menopause which occurs in the early 40s. Thanks to the rapid progression science has made in this field, we now know that, in addition to these two diseases which are strongly associated with the existence of an incomplete mutation of gene FMR1, there is a wide spectrum of clinical manifestations that could indicate the presence of a mutation in the FMR1 gene. During the 70s and 80s, the only available laboratory tests which were used for diagnosing Fragile X syndrome where chromosomal (cytogenetic) tests. The application of these tests was useful, but very often imprecise. During the 90s, after the FMR1 had been discovered, whose mutations lead to Fragile X associated disorders, more precise genetic tests were developed. Today, the application of modern genetic diagnostic tests is considered standard practice in identifying mutations in the FMR1 gene. The use of modern tests can detect more than 99% persons, of both sexes, with this mutation.

Finally, the intensive evolvement of this medical and scientific field has enabled the rapid development of drugs aimed at discovering targeted therapies that would resolve the key changes, at the cellular level, occurring in Fragile X syndrome. The majority of clinical studies are focused on researching drugs for Fragile X syndrome. Although no drug has yet been registered for Fragile X syndrome, many drugs are in development, and some have shown excellent effects in Fragile X syndrome. Targeted therapy is anticipated, and it is believed that the discovery of targeted pharmacological therapy for Fragile X syndrome will also be significant for the development of drugs for other neurodevelopmental disorders. The therapy, which is applied today, is based on non–pharmacological measures (speech therapy, physical therapy, behavioral therapy, occupational therapy, etc.) and medications aimed at managing symptoms (symptomatic therapy). The goal of the seminar is to present non–pharmacological and pharmacological treatment options that are effective in treating Fragile X–associated conditions. Additionally, we emphasized the importance of proper monitoring of children with Fragile X syndrome.