Fragile XE syndrome

Alternate names

FRAXE syndrome; Fragile site, folic acid type

Definition

Fragile XE syndrome (FRAXE) is a genetic condition associated with mild to borderline intellectual disabilities with physical features differing from person to person.

Cause

• FRAXE is a genetic disorder caused by mutations in the AFF2 gene.
• This gene provides instructions for making a protein whose function is not well understood.
• Nearly all cases of FRAXE are caused by a specific type of mutation, called a trinucleotide repeat.
• A trinucleotide repeat is an abnormal expansion of three repeats of our DNA building blocks (nucleotides).
• The repeating nucleotides in FRAXE are CCG.
• Normally, the involved segment of three nucleotides is repeated approximately 4 to 40 times.
• However, in people with FRAXE, the CCG segment is repeated more than 200 times, which makes this region of the gene unstable or fragile.
• As a result, the AFF2 gene is turned off (silenced), and no AFF2 protein is produced.
• It is unclear how a shortage of this protein leads to intellectual disability in people with FRAXE.
• Some people with FRAXE have a deletion of genetic material in the AFF2 gene.
• People with 50 to 200 CCG repeats are said to have an AFF2 gene premutation.
• Current research suggests that people with a premutation do not have associated cognitive problems.

Inheritance

FRAXE is inherited in an X-linked manner.

Signs and symptoms

• It is a genetic condition associated with mild to borderline intellectual disabilities with physical features differing from person to person.
• The characteristic features are learning difficulties, often a consequence of communication problems (speech delay, poor writing skills), hyperactivity, and a shortened attention span.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Aggressive behavior(Aggression)
• Agitation
• Autistic behavior
• Clumsiness
• Delayed speech and language development(Deficiency of speech development)
• Epicanthus(Eye folds)
• Hoarse voice(Hoarseness)
• [[Hyperactivity](More active than typical)
• Impulsivity(Impulsive)
• Intellectual disability(Mental deficiency)
• Intrauterine growth retardation(Prenatal growth deficiency)
• Obsessive-compulsive behavior(Obsessive compulsive behavior)
• Prominent ear helix
• Prominent nasal bridge(Elevated nasal bridge)
• Recurrent hand flapping
• Short stature(Decreased body height)
• Specific learning disability
• Thick vermilion border(Full lips)

5%-29% of people have these symptoms

• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Macrocephaly(Increased size of skull)
• Stereotypical body rocking

Diagnosis

The diagnosis of FRAXE is made based on signs and symptoms and genetic testing to confirm either a trinucleotide repeat expansion or a deletion within the AFF2 gene.

Treatment

• Although there is no specific treatment for FRAXE, there may be ways to manage the symptoms.
• A team of doctors or specialists is often needed to figure out the treatment options for each person.

NIH genetic and rare disease info

• NIH info on Fragile XE syndrome

Fragile XE syndrome is a rare disease.

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