Facts about Fragile X Syndrome

Fragile X syndrome is a genetic disease caused due to mutation in the Fragile Mental Retardation 1 (FMR1) gene of the X chromosome. This gene is responsible for coding a specific protein (FMRP) required for the development of brain.

FMRP plays an important role in cell communication. The arm of the chromosome with the mutated gene contains repetitive sequences (can be more than 200) of the same codon. In such a condition, there is little or no production of the protein, resulting in the symptoms of fragile X syndrome.

The length of the repeat sequence can be short, medium, or long. Most of the time, the size of the repeat length is short. The long repeat size is described as a full mutation. The more the number of repetition, the severe is the syndrome.

The FMR1 gene becomes faulty only when the number of repeated code words increases over a critical number. When the repeat size is medium, the person may have a working copy of the gene. In such cases, he/she is a premutation carrier. Males and females with 55 to 200 repeats of the CGG segment are said to have an FMR1 gene premutation.

He/she will not develop fragile X syndrome (or may have mild versions of the symptoms such as anxiety and depression). Such men and women may develop a neurological condition after about 75 years of age. These women may experience premature ovarian failure (early menopause).

• According to medical researches, fragile X syndrome is the most common inherited cause of developmental disability. It occurs in approximately 1 in 4,000 males and 1 in 8,000 females. The symptoms of this syndrome are more severe in boys as compared to girls.

• Mutation for this syndrome occurs in the sex-linked chromosome. This syndrome is more common among males than females. The symptoms can be less severe such as mild learning disabilities (due to shyness and social anxiety) or severe cognitive impairment and autism.

• The syndrome is inherited from carrier parents. Since females have two X chromosomes (XX), a baby girl with FMR1 mutation in one X chromosome will be a carrier of this syndrome. She might be mildly affected with fragile X syndrome depending on how many of her cells are expressing the faulty FMR-1 gene copy. 

One copy of the altered gene in each cell can result in fragile X syndrome. In males (they have X and Y chromosomes) too, a mutation in a gene in each cell can cause the disorder.

• In women, the FMR1 gene premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs. So, women with the premutation have an increased risk of having a child with fragile X syndrome. However, the premutation in men does not expand to more than 200 repeats as it is passed to the next generation.

• Men will pass the premutation only to their daughters. Their sons receive a Y chromosome (and not the X), which does not have the FMR1 gene. In simple words, a male with this syndrome will have normal sons (X chromosome is derived from the mother, and not the father) and carrier daughters (as father passes on an X chromosome to all his daughters).

• A daughter may inherit two working copies of the X-linked genes, one from her father and one from her mother. In this case, she will not be affected by the condition, and she will also not be a carrier of the X-linked recessive faulty gene. Similarly, if the son inherits working copy of the X-linked gene from a carrier mother and Y chromosome from his father, he will not be affected.

• Fragile X syndrome is hereditary, and is passed from parents to the offspring. A boy born to a carrier mother and normal father either suffers from this syndrome or is unaffected (only boys with a full mutation will have fragile X syndrome), whereas a girl born to the same parents is either a carrier of the syndrome or will develop the syndrome.

• The symptoms of fragile X syndrome can be mild at birth, they may progress afterward. At times, children with this syndrome may appear normal at infancy, and they may exhibit typical characteristics later. Some of the physical characteristics manifested by individuals having this syndrome are large prominent ears, elongated face with a prominent jaw, highly flexible joints, and enlarged testes.

• The syndrome encompasses a group of mental disorders such as hyperactivity, mental retardation, lack of attention, intellectual disability, repetition of activities, and other emotional, social, and behavioral problems. The symptoms of learning disability may range from mild learning problem to severe intellectual disorders.

A delay in the development of physical skills and coordination difficulties can be noticed.

Other signs and symptoms include aversion to touch, loud noises, bright lights, and strong smells, gaze aversion, anxiety and mood instability (both aggression and depression can be noticed), balance problems, speech delay, speech disturbances, hand flapping and biting, etc.

• The syndrome can be detected through a simple blood test. It is diagnosed by conducting genetic testing. It is a lifelong condition and there is no cure. However, it does not shorten lifespans. Therapy for this syndrome aims at improving the quality of life and managing the symptoms. 

Along with certain medication, the physician may recommend special education, and speech or behavioral therapy in order to manage the symptoms.

DNA testing also helps identify the individuals who are carriers of fragile X syndrome. The individuals having a family history of this syndrome can opt for genetic counseling. They should know the facts about the fragile X syndrome. Doing so will help in assessing the possibilities of having children with this syndrome.

Nowadays, sophisticated techniques are available to determine genetic abnormalities in a developing fetus. With the understanding of the underlying causes, DNA researchers are trying to find out a cure for the syndrome. They are also trying to design strategies which can help prevent the occurrence of the syndrome.

Disclaimer: The information provided in this story is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.