Fragile X syndrome (FXS) is a hereditary disorder of the X chromosome. FXS is the most common cause of inherited mental retardation and the most common known cause of autism. FXS affects 1 in 4000 males and 1 in 6000 females.

FXS is caused by mutations of the FMR1 gene. These mutations interfere with the normal development of certain parts of the brain and body by affecting the production of a normal body substance called “fragile X mental retardation protein” (FMRP). In the absence of FMRP, neural connections in the brain cannot be made properly and affected children do not fully develop some higher cognitive functions.

A risk factor is something that increases your chance of getting a disease or condition.

The main risk factor for FXS is having a parent with an FMR1 mutation. These mutations vary in degree. Most people who inherit a minor mutation, which is sometimes called a premutation, do not develop the symptoms and signs of FXS, though a few premutated children may show signs resembling autism, and others (primarily males) may develop a set of neurological symptoms called “fragile X tremor ataxia syndrome” in later adult life.

However, children of mothers with FMR1 premutations are at risk of inheriting a fully mutated FMR1 gene severe enough to cause symptomatic FXS. If a woman is an asymptomatic carrier of an FMRI mutation or premutation, each child of hers has a 50% chance of inheriting that gene. Of the children that inherit that gene, boys are much more likely to develop symptoms than girls, although the severity of the disorder may be quite variable between different individuals.

In general, each subsequent generation tends to have worse mutations and a higher risk of FXS than the previous one.

The number and severity of symptoms varies widely. Symptoms tend to be less frequent and milder in females. Symptoms can include:

• Mental impairment ranging from learning disabilities to mental retardation
• Behavioral difficulties, including:
  • Attention deficit hyperactivity disorder (ADHD)
  • Anxiety
  • Unstable moods and emotional outbursts
  • Aggressive behavior
  • Extreme shyness (particularly in girls)
• Autistic behaviors
• Physical problems and abnormalities, including:
  • Long face with protruding jaw
  • Large, protruding ears
  • Flat feet
  • Hyperextended joints
  • High-pitched voice and enlarged testes in males after puberty
  • Mitral valve prolapse
  • Seizures

The doctor will ask about symptoms and medical history, and perform a physical exam. FXS may be suspected if a child has:

• Physical, cognitive, or emotional symptoms of FXS
• Unexplained developmental delays or mental retardation

The diagnosis can be confirmed by a DNA blood test or increasingly by direct analysis of FMRP in hair or blood.

There is no cure for FXS. Treatment is aimed at controlling symptoms. Treatment may include:

Medications used to treat symptoms of FXS include:

• Stimulants (such as Ritalin) and other medications to treat hyperactive behavior
• Psychotherapeutic drugs (such as Prozac) to help control:
  • Anxiety
  • Aggression
  • Emotional outbursts
• Anticonvulsants (such as carbamazepine) to control seizures

Scientists are currently trying to understand how FMRP works in the body so that specific treatments may someday prove possible. Unfortunately even the possibility of such treatment remains far in the future.

Specific educational strategies depend on the degree of developmental delays and/or mental retardation. Educational strategies include setting a stable educational environment for the patient that includes:

• School work that only requires a short attention span
• Minimal distractions
• Predictable activities and classroom routine
• Close communication between parent and school
• Emphasis on functional life skills