Fragile X Syndrome Workup

Updated: Aug 15, 2022
  • Author: Jennifer A Jewell, MD, MS; Chief Editor: Maria Descartes, MD  more...
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Imaging Studies

Radiography of the spine is recommended in patients with fragile X syndrome to evaluate for scoliosis.

Echocardiography is recommended to exclude mitral valve prolapse.


Other Tests

Cytogenetic testing for fragile X syndrome is not as sensitive as molecular testing, with a false-negative result rate of approximately 20%. Thus, DNA testing for fragile X syndrome is recommended. Karyotyping may reveal other chromosomal anomalies, and both a standard karyotype and DNA testing are suggested when a possible diagnosis of fragile X syndrome is considered.

The criterion standard diagnostic test involves molecular genetic techniques that detect the FMR1 gene. The exact number of CGG triplet repeats can be determined. Southern blot and polymerase chain reaction (PCR) are the 2 methods of genetic analysis that are currently available. Southern blot analysis provides a more accurate estimation of the number of CGG triplet repeats if a full mutation is present (with a large CGG expansion). It can also be used to evaluate the degree of methylation at the CGG repeat site.

PCR is faster, requires a minimal sample, and is less expensive than Southern blot analysis. Additionally, PCR more accurately estimates the number of CGG triplet repeats if a premutation is present (with small-to-moderate increases in CGG repeats). More recent success with fluorescent methylation-specific PCR and GeneScan analysis may further expand diagnostic options.

A comprehensive developmental evaluation by a speech and language therapist, physical therapist, and occupational therapist is recommended to assess weaknesses and to identify areas in which improvement is needed most. As the patient matures, repeat evaluation may be necessary.

Ophthalmology examinations are required.

Routine auditory examinations are advised; otolaryngology referral for chronic otitis media and evaluation for pressure equalization (PE) tube placement are recommended.