Fragile X Syndrome - Description

Page Contents

• Other Names
• ICD-9
• Description
• Genetics
• Prognosis
• Prevalence
• Impact
• Pearls And Alerts
• Helpful Articles

Other Names

Martin Bell syndrome

ICD-9

759.83, Fragile X syndrome

See Fragile X ICD9 ( 45 KB) for associated condition codes.

Description

Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene of the X chromosome, is the most common form of inherited mental retardation. The FXS phenotype is usually more apparent in males than in females. The following phenotypic descriptions are from FMR-1-related disorders (GeneReviews).

The classic phenotype of FXS in males includes:

• mental retardation, with an average IQ of 50 and a range of 25-90, with most under 70 [Alanay: 2007];
• behavioral features similar to those seen in autism
• macrocephaly
• characteristic facies including long narrow face with prominent chin, tall forehead, flat nasal bridge, and large pinnae (these features may be subtle)
• flexible finger joints and flat feet
• postpubertal macroorchidism
  

Females with fragile X generally have milder manifestations, although they may have:

• some similar physical features, particularly large or prominent ears, flexible finger joints, and flat feet
• learning problems in the majority
• short attention span
• moodiness, shyness, anxiety
• mental retardation in 30%

The phenotypes of FXS are not always clinically distinct and the classic facial appearance, even in males with the full mutation, is subtle, especially in early childhood. Testing for the FMR1 gene mutation is recommended in boys and girls with developmental delay/mental retardation and/or autistic features, especially if they also have any phenotypic features or relatives with FXS or undiagnosed mental retardation (see Fragile X testing (GeneTests)). Also see the practice parameter for evaluation of the child with global developmental delay, published in 2003 – [Shevell: 2003].

Genetics

• FXS is due to a mutation on the X chromosome which, in the full-blown syndrome, inactivates the FMR-1 gene, stopping production of the FMR-1 protein (FMRP).
• The mutation involves an expansion of a CGG sequence repeat in an untranslated region of the FMR-1 gene.
• FMR-1 related disorders include adult onset fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related premature ovarian failure in premutation carriers. These disorders may result from elevated mRNA levels in premutation carriers. [Hagerman: 2004]
• Prenatal testing – amniocentesis and chorionic villus sampling (CVS) – is available for mothers who already have a child with FXS and are confirmed premutation carriers. Determining the methylation pattern of the gene may be impossible in cells obtained by CVS, making the distinction between large premutations and smaller full mutations difficult and limiting the potential for clinical correlation. Follow-up amniocentesis is recommended after CVS.

See the Genetics of fragile X syndrome Issue page for more information.

Prognosis

Life expectancy is normal. Clinical features vary widely in children with FXS and adult functioning will depend on IQ and the presence or absence of autistic behaviors.

Prevalence

The prevalence of FXS is between 1 in 4,000 to 1 in 5,000 males in Caucasian populations, and may be as high as 1 in 2,500 males in African-derived populations. Prevalence in females is unknown, but is estimated to be between 1 in 8,000 and 1 in 9,000. [Crawford: 2001] Female carriers are thought to be very common; with a range from 1 in 100 to 1 in 250. See FMR-1-related disorders (GeneReviews).

Impact

The fragile X syndrome is the most common form of inherited mental retardation, accounting for approximately 40% of cases with X-linked mental retardation. A screening study in a U.S. public special education population suggests that approximately 1 in 400 males receiving special education services are affected by the fragile X syndrome. [Crawford: 2001]

Pearls And Alerts

Helpful Articles

PubMed search for articles on Fragile X Syndrome in the last 3 years.

Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, Kronk R, Delahunty C, Hessl D, Visootsak J, Picker J, Gane L, Tranfaglia M.
Advances in the treatment of fragile X syndrome.
Pediatrics. 2009;123(1):378-90. PubMed abstract

Fragile X Syndrome Module Authors

The authors listed above are responsible for the overall Fragile X Syndrome Module. Authors contributing to individual pages in the module are listed on those pages.

Page Bibliography

Alanay Y, Unal F, Turanli G, Alikaşifoğlu M, Alehan D, Akyol U, Belgin E, Sener C, Aktaş D, Boduroğlu K, Utine E, Volkan-Salanci B, Ozusta S, Genç A, Başar F, Sevinç S, Tunçbilek E.
A multidisciplinary approach to the management of individuals with fragile X syndrome.
J Intellect Disabil Res. 2007;51(Pt 2):151-61. PubMed abstract

Crawford, DC.
FMR1 and the Fragile X Syndrome.
CDC: National Office of Public Health Genomics; HuGENet: Fact Sheets; (2001) http://www.cdc.gov/genomics/hugenet/factsheets/FS_FragileX.htm. Accessed on 1/3/2009.

Hagerman PJ, Hagerman RJ.
The fragile-X premutation: a maturing perspective.
Am J Hum Genet. 2004;74(5):805-16. PubMed abstract / Full Text

Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, Majnemer A, Noetzel M, Sheth RD.
Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society.
Neurology. 2003;60(3):367-80. PubMed abstract / Full Text