Written by Bahar Madani
Learn how the Fragile X Syndrome causes intellectual disabilities including learning disabilities and cognitive impairment. This article provides an overview on what regions of the brain become affected, and how mutations in the FMR1 gene are passed down.
The Fragile X Syndrome has two alternative names: Martin Bell- Syndrome and the Escalante Syndrome. These two names were chosen in In 1943 when James Purdon Martin and Julia Bell first described fragile X syndrome as a form of sex-linked mental retardation that is inherited from the X-chromosome of a mother carrying the trait or an affected father (X-linked). They reported a family case study in which intellectual disability appeared to be inherited and linked to the X chromosome. The syndrome was initially named Martin-Bell syndrome after its discoverers, but the name was changed to Fragile X syndrome.
Fragile X syndrome causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females. Affected individuals usually have delayed development of speech and language by age 2.
Researchers at the Stanford University School of Medicine have identified several large-scale neural systems in the brain that appear to be impaired by fragile X syndrome, the most common form of inherited intellectual disability.
The neural systems the researchers identified include the language, visuospatial, and salience networks. The salience network is thought to be involved in evaluating emotional stimuli and generating appropriate responses. Individuals with fragile X syndrome experience difficulties communicating, switching between tasks, and regulating their stress levels. The neural network exhibiting the greatest impairment was the salience network, the researchers say.
As can be seen in this composite image from the study, there are brain regions, depicted in green, in which gray-matter volume increased more in children with fragile X than in children in a control group during the two-year period between imaging sessions.
Fragile X results from a change or mutation in the Fragile X Mental Retardation 1 (FMR1) gene, which is found on the X chromosome. The gene normally makes a protein called Fragile X Mental Retardation Protein, or FMRP. In women, the FMR1 gene premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs. This means that women with the premutation have an increased risk of having a child with fragile X syndrome, whereas, the premutation in men does not expand to more than 200 repeats as it is passed to the next generation. Men pass the premutation only to their daughters. Their sons receive a Y chromosome, which does not include the FMR1 gene.
Nearly all cases of fragile X syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times.
The features of one who is affected by the fragile x syndrome may be hard to recognize in babies and young children but sometimes become more apparent with age. Below are examples of some of the features that may appear. Not everyone with Fragile X has all these signs.
long face
large prominent ears,
flat feet
hyperextensible joints, especially fingers
low muscle tone
soft skin
large forehead
Life expectancy for people with fragile X syndrome is generally normal. Many affected people participate in an active lifestyle and have good health. Some people are more prone to a number of medical problems, such as ear infections and/or seizures.
There is no single treatment for Fragile X syndrome, but there are treatments that help minimize the symptoms of the condition. Individuals with Fragile X who receive appropriate education, therapy services, and medications have the best chance of using all of their individual capabilities and skills. But at present, there is no cure.
Sources:
Claudia Bagni,1,2,3 Flora Tassone,4,5 Giovanni Neri,6 and Randi Hagerman5,7. “Fragile X Syndrome: Causes, Diagnosis, Mechanisms, and Therapeutics.” The Journal of Clinical Investigation, 3 Dec. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3533539
“Diagnosis of Fragile X Syndrome.” Further Information Neurological Disorder, www.findresources.co.uk/the-syndromes/fragile-x/diagnosis.
“Fragile X Syndrome – Symptoms and Signs.” Fraxa Research Foundation, www.fraxa.org/fragile-x-syndrome/symptoms.
“Are There Treatments for Fragile X Syndrome?” Fraxa Research Foundation, www.fraxa.org/fragile-x-syndrome/treatment.
“What Are the Treatments for Fragile X Syndrome?” Eunice Kennedy Shriver National Institute of Child Health and Human Development, www.nichd.nih.gov/health/topics/fragilex/conditioninfo/treatments#:~:text=There%20is%20no%20single%20treatment,their%20individual%20capabilities%20and%20skills.
“Fragile X Syndrome.” National Organization of Rare Disorders, rarediseases.org/rare-diseases/fragile-x-syndrome.
“About Fragile X Syndrome.” National Human Genome Research Institute, www.genome.gov/Genetic-Disorders/Fragile-X-Syndrome.