Rare Disease Report

Fragile X Syndrome: Rare Disease Quick Facts

OCTOBER 12, 2014

Fragile X syndrome (aka Martin–Bell syndrome, or Escalante's syndrome) is a genetic condition that results in a range of physical, social, and intellectual disabilities. It is also the most common genetic cause of autism – seen in 5% of autistic children.

Fragile X syndrome is associated with the expansion of the CGG dinucleotide repeat affecting the Fragile X mental retardation I (FMR1) gene on the X chromosome. This mutation leads to improper expression of the fragile X mental retardation protein (FXRP) . 

Since the disease is a X linked genetic condition, it is predominantly seen in males and they tend to have more severe symptoms (females will have a second intact X gene to compensate for any mutations on one gene).


intellectual disability
  • Average IQ in males 40. Higher in females and may approach normal (100)
Behavioral / neurological
  • Speech impaired
  • Hand flapping
  • Shyness
  • Limited eye contact
  • Memory problems
  • Attention deficit hyperactivity disorder
  • Hypersensitivity to visual, auditory, tactile, and olfactory stimuli.
  • Speech impaired
  • Other ‘autistic-like’ behaviors


  • Large, protruding ears (one or both)
  • Long face
  • High-arched palate
  • Hyperextensible finger joints
  • Hyperextensible ('Double-jointed') thumbs
  • Flat feet
  • Soft skin
  • Postpubescent macroorchidism
  • Hypotonia


Prenatal testing for FMR1 mutations can be performed.
If Fragile X syndrome is suspected (unexplained delayed development in infants/toddlers) the family can be referred to a genetics counselor to perform a genetic test fo fragile X syndrome.


There is currently no specific orphan drug approved for fragile X syndrome and many of the treatments in place are similar to those used for autistic children. These include special educational care, possible dietary restritions, behavioral therapies, etc.

Medications for anxiety, aggressive behavior, mood disorders, ADHD, perseverative behaviors etc have been tested in limited number of studies. Clinicians should refer to  Fragile X Clinical & Research Consortium for guidance on what may be the best treatment options for these symptoms.

Drugs in Development

There are currently 11 drugs with orphan designation for treatment of fragile X syndrome or behavioral abnormalities associated with fragile X syndrome. To date, the FDA has approved none. Further, there have recently been some clinical studies with disappointing results that have led companies such as Novartis, Seaside Therapeutics, and Roche to no longer pursue those drugs for possible approval.
There are currently four phase 2 studies recruiting patients with fragile X syndrome.
NNZ-2566 (Neuren Pharmaceuticals)
Metadoxine (Alcobra Pharma)
Acamprosate (Confluence Pharmaceuticals)
Ganaxolone (Marinus Pharmaceuticals) (not orphan designatiated).

Advocacy and Research Nonprofit Organizations

National Fragile X Foundation http://www.fragilex.org/
FRAXA Research Foundation http://www.fraxa.org/

 Cartoon of a 'typical' boy with fragile X syndrome courtesy wikimedia commons.


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