You are referred a 6 year old boy due to concerns about a potential learning disability. Physically, he appears normal other than for a slightly elongated face. During conversation you find him difficult to follow. He speaks in bursts with disruptions in the flow giving a cluttered quality to his speech. Which of the following trinucleotide repeats sequence disorders would you suspect?
Exam Question Oct 2014
The description is consistent with Fragile X syndrome.
Exam Question Oct 2014
The description is consistent with Fragile X syndrome.
Fragile X Syndrome
Fragile X is a genetic syndrome characterised by mental retardation, an elongated face, large protruding ears, and large testicles (in men).
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They tend to be shy, avoid eye contact, and have difficulties reading facial expressions. They often display stereotypic movements such as hand flapping.
Fragile X is the most common inherited cause of learning disability.
The speech of affected individuals of often abnormal. Of note are abnormalities of fluency (flow). Such speech is often referred to as cluttered.
It is an X-linked dominant disorder caused by the amplification of a CGG repeat in the 5 untranslated region of the fragile X mental retardation 1 gene (FMR1). These CGG repeats disrupt synthesis of the fragile X protein (FMRP) known to be essential for brain function and growth. The gene is located at Xq27. As with other trinucleotide repeat disorders (Huntington's, myotonic dystrophy, Friedreich's ataxia, and spinocerebellar ataxia) the greater number of repeats the more severe the condition.
The fragile X phenotype typically involves a variety of psychiatric symptoms, including features of autism, attention deficit/hyperactivity disorder, anxiety, and aggression.
Females as well as males are affected. This is through the process of X-inactivation, where one X in each female cell inactivates itself. Males are more severely affected because they have only one X chromosome.
It has a prevalence estimate of 1/3600-4000.
