Fragile X Syndrome (FXS) is the most common inherited, single gene cause of intellectual disability and autism worldwide. FXS can cause intellectual disabilities, attention deficit and hyperactivity, autism, autistic features, speech delay .It is a genetically-defined inherited condition that can be diagnosed by a DNA blood test. It is estimated that 5 per cent of people with a diagnosis of an Autism Spectrum disorder also have Fragile X syndrome. Fragile X syndrome occurs in both genders, males are generally affected with greater severity. Life expectancy is not affected in people with FXS because there is usually no life-threatening health concerns associated with the condition.
Fragile X-associated disorders are a family of genetic conditions that can affect individuals in a variety of ways. The conditions are all caused by changes in the gene known as FMR1. Fragile X Syndrome (FXS) is caused by a full mutation of the FMR1 gene. Fragile X-associated tremor/ataxia syndrome (FXTAS) and Fragile X-associated primary ovarian insufficiency (FXPOI) are caused by a permutation of the FMR1 gene.
Fragile X–associated tremor/ataxia syndrome is an “adult onset” neurodegenerative disorder, usually affecting males over 50 years of age. Females comprise only a small part of the FXTAS population, and their symptoms tend to be less severe. FXTAS affects the neurologic system and progresses at varying rates in different individuals. All individuals with FXTAS are permutation carriers of the FMR1 gene. Researchers believe that having the permutation leads to the overproduction of FMR1 mRNA .They believe that the high levels of mRNA are what cause the signs and symptoms of FXTAS Fragile X-associated primary ovarian insufficiency, one of three known Fragile X-associated disorders caused by changes in the FMR1 gene, is a condition in which the ovaries are not functioning at full capacity in an FMR1 permutation carrier. FXPOI occurs in about 20-25% of adult female FMR1 permutation carriers. It has also been reported in teenagers who are carriers.
There have been a number of studies aimed at determining the prevalence of FXS in males and females. Prevalence of FXS in males is approximately 1 in 3,600 to 4,000 and in females is approximately 1 in 4,000 to 6,000. It is estimated that 5 per cent of people with a diagnosis of an Autism Spectrum disorder also have Fragile X syndrome. It is estimated that in India we have approximately 4 lakh children with FXS, most of whom are undiagnosed and untreated.
Fragile X syndrome is caused by the expansion of the FMR1 gene on the X chromosome, known as a gene mutation. In some people, this gene may contain between 50 and 200 repeats. This is called a Fragile X permutation. A person with this permutation is called a ‘carrier’. Fragile X is caused when this gene lengthens to over 200 repeats interfering with the normal production of this protein and therefore normal brain development.
The Fragile X gene may be passed down through each generation. Daughters born to male carriers will inherit their fathers affected X chromosome and they will also be carriers. Sons born to male carriers will not inherit their fathers X chromosome and therefore will not be affected by Fragile X. Because females have two X chromosomes, children of either sex born to female carriers have a 50% chance of inheriting the affected gene. If they inherit the affected gene they will either be a carrier or have full mutation Fragile X. The Fragile X mutation often increases when passed from mother to child and down through the generations of a family. This means that children born with Fragile X frequently appear in families with no previous history of intellectual disability.
Signs and Symptoms
The way that Fragile X syndrome affects people will vary. Girls and women are usually less affected than boys and men. A person may be fully affected by Fragile X but not show all of these signs.
Fragile X Syndrome
Behavioural characteristics – They include ADD, ADHD, autism and autistic behaviours, social anxiety, hand-biting and/or flapping, poor eye contact, sensory disorders, and increased risk for aggression.
Intellectual disabilities – FXS include a range from moderate learning disabilities to more severe intellectual disabilities. The majority of males with Fragile X syndrome demonstrate significant intellectual disability.
Physical features – Include large ears, long face, soft skin, and large testicles (called “macroorchidism”) in post-pubertal males. Connective tissue problems may include ear infections, flat feet, high arched palate, double-jointed fingers, and hyper-flexible joints. No one individual will have all the features of FXS, and some features, such as a long face and macroorchidism, are more common after puberty.
Disposition-They are also very social and friendly, have excellent imitation skills, have a strong visual memory/long term memory, like to help others, are nice, thoughtful people and have a wonderful sense of humour.
Behavioural characteristics – It’s seen in males and also can be seen in females, though females often have milder intellectual disability and a milder presentation of the syndrome’s behavioural and physical features.
Intellectual disabilities- About one-third of females with FXS have a significant intellectual disability. Others may have moderate or mild learning disabilities, emotional/mental health issues, general anxiety, and/or social anxiety.