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Diseases

Genetic and Rare Diseases Information Center (GARD)

Other Names for this Disease
  • Fra(X) syndrome
  • FRAXA syndrome
  • FXS
  • Marker X syndrome
  • Martin-Bell syndrome
More Names
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Overview



What is fragile X syndrome?

What are the symptoms of Fragile X syndrome?

What causes fragile X syndrome?

How is fragile X syndrome inherited?

Is genetic testing available for fragile X syndrome?

¿Qué significa ser portador de la premutación del síndrome X frágil?

¿Cuáles son las señales y síntomas que se presentan en una persona con la premutación para el síndrome X frágil?


What is fragile X syndrome?

Fragile X syndrome is a genetic condition involving changes in part of the X chromosome.[1] This condition causes a range of developmental problems including learning disabilities and cognitive impairment.[2] It is the most common form of inherited intellectual disability in males and a significant cause of intellectual disability in females.[1]  Fragile X syndrome is caused by a change in the FMR1 gene.[1][2] Fragile X syndrome is inherited in an X-linked dominant pattern.[2]
Last updated: 6/23/2011

What are the symptoms of Fragile X syndrome?

Fragile X syndrome is characterized by developmental problems, including delayed development of speech and language, and mild to moderate intellectual disability. Usually, males are more severely affected than females. Additional features may include anxiety and hyperactive behavior such as fidgeting or impulsive actions, attention deficit disorder (ADD), features of autism spectrum disorders that affect communication and social interaction, and seizures. Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty.[2]
Last updated: 6/5/2013

What causes fragile X syndrome?

Mutations (changes) in the FMR1 gene cause fragile X syndrome. This gene carries instructions to make a protein called the fragile X mental retardation 1 protein. In most cases of fragile X syndrome, a specific DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times. The abnormally expanded CGG segment turns off (silences) the FMR1 gene, which in turn disrupts nervous system functions and leads to the signs and symptoms of fragile X syndrome. In a small percentage of cases, other types of mutations cause fragile X syndrome. These mutations delete part or all of the FMR1 gene, or change one of the building blocks (amino acids) used to make the gene's protein. As a result, no protein is produced, or the protein's function is impaired because its size or shape is altered.[3]

Males and females with 55 to 200 repeats of the CGG segment are said to have an FMR1 gene premutation. Most people with a premutation are intellectually normal. In some cases, however, individuals with a premutation have lower than normal amounts of the fragile X mental retardation 1 protein. As a result, they may have mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience emotional problems such as anxiety or depression. Some children with a premutation may have learning disabilities or autistic-like behavior. About 20 percent of women with a premutation have premature ovarian failure, in which menstrual periods stop by age 40. Men, and some women, with a premutation have an increased risk of developing a disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder is characterized by progressive problems with movement (ataxia), tremor, memory loss, loss of sensation in the lower extremities (peripheral neuropathy), and mental and behavioral changes.[3]
Last updated: 6/15/2011

How is fragile X syndrome inherited?

Fragile X syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes (the Y chromosome is the other sex chromosome). The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. In women, the FMR1 gene premutation (approximately 55 to 200 repeats) on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs that contribute to offspring. This means that women with a premutation (or a full mutation) have an increased risk of having a male or female child with fragile X syndrome. The magnitude of this risk is related to the number of CGG repeats identified.[4] By contrast, the premutation in men does not expand to more than 200 repeats as it is passed to the next generation, and the vast majority of males with a full mutation have fragile X syndrome.[3][4] Men pass the premutation on to all of their daughters and none of their sons.[4] Their sons receive a Y chromosome, which does not include the FMR1 gene.[3] However, there is a risk for fragile X syndrome in a male premutation carrier's grandchildren through his daughters.[4] This is why fragile X syndrome is typically passed on through the mother to her son.
Last updated: 6/15/2011

Is genetic testing available for fragile X syndrome?

Yes, genetic testing is available for fragile X syndrome. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the diagnosis of an FMR1-related disorder (including fragile X syndrome) has been confirmed in a family member.[5] GeneTests lists the names of laboratories that are performing genetic testing for fragile X syndrome. To view the contact information for the clinical laboratories conducting testing, click here. To access the contact information for the research laboratories performing genetic testing, click here. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, those interested in learning more may need to work with a health care provider or a genetics professional.
Last updated: 6/15/2011

¿Qué significa ser portador de la premutación del síndrome X frágil?

Las personas que tienen de 55 a 200 repeticiones del trinucleótido CGG son portadores de una premutaciόn en el gen FMR1. Mujeres con la premutaciόn tienen un riesgo elevado sobre la población general de desarrollar el síndrome de temblor y ataxia asociado a síndrome del cromosoma X frágil (FXTAS, por sus siglas en inglés) y menopausia prematura o precoz. Todos los hijos de estas mujeres tienen un riesgo elevado de tener el síndrome X frágil, FXTAS, y, si son hembras de desarrollar menopausia prematura. Varones con la premutaciόn también tienen un riesgo elevado de presentar con FXTAS. Hombres con FXTAS solamente transmiten la premutaciόn a sus hijas, como el gen esta localizado en el cromosoma X. [6]
Last updated: 9/10/2013

¿Cuáles son las señales y síntomas que se presentan en una persona con la premutación para el síndrome X frágil?

La mayoría de personas con premutaciones son intelectualmente normales, pero en algunos casos las personas pueden presentar niveles bajos de la proteína FMRP y presentar una forma leve des síndrome X frágil. Los signos y síntomas pueden incluir: orejas prominentes, problemas emocionales (ansiedad o depresión), algún nivel de icapacidad o desorden del comportamiento o aprendizaje y comportamiento parecido al autismo. [7] Un 20% de las mujeres con premutación desarrollan falla en los ovarios y menopausia prematura. [8] Hombres, como mujeres, con una premutaciόn tienen un riesgo más alto que la población en general de desarrollar el síndrome de temblor y ataxia asociado al síndrome del cromosoma X frágil (FXTAS, por sus siglas en inglés). Este trastorno es caracterizado por ataxia, temblor, pérdida de memoria, neuropatía periférica, alteraciones mentales y del comportamiento. [6]
Last updated: 3/21/2014

References
  1. Haldeman-Englert C. Fragile X syndrome. MedlinePlus. 2007; http://www.nlm.nih.gov/medlineplus/ency/article/001668.htm. Accessed 4/20/2009.
  2. Fragile X syndrome. Genetics Home Reference (GHR). April 2012; http://www.ghr.nlm.nih.gov/condition/fragile-x-syndrome. Accessed 6/5/2013.
  3. Fragile X syndrome. Genetics Home Reference. May 2007; http://ghr.nlm.nih.gov/condition/fragile-x-syndrome. Accessed 6/15/2011.
  4. What Does it Mean to be a Carrier?. The National Fragile X Foundation. September 30, 2008; http://www.fragilex.org/html/carriers.htm. Accessed 6/15/2011.
  5. Robert A Saul, Jack C Tarleton. FMR1-Related Disorders. GeneReviews. October 28, 2010; http://www.ncbi.nlm.nih.gov/books/NBK1384/. Accessed 6/16/2011.
  6. Saul RA, Tarleton JC. GeneReviews. April 26, 2012; http://www.ncbi.nlm.nih.gov/books/NBK1384/. Accessed 9/10/2013.
  7. Fragile X Syndrome. Genetics Home Reference. May 2007; http://ghr.nlm.nih.gov/condition/fragile-x-syndrome. Accessed 2/8/2010.
  8. Fragile X Syndrome. March of Dimes. April 2010; http://www.marchofdimes.com/Baby/birthdefects_fragilex.html. Accessed 2/8/2010.