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Disease Profile

Fragile X syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Neonatal

ICD-10

Q99.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Marker X syndrome; Martin-Bell syndrome; FRAXA syndrome;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Endocrine Diseases;

Summary

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] Other signs and symptoms may include symptoms of autism spectrum disorders, seizures, and characteristic physical features.[2] Fragile X syndrome is caused by a change (mutation) in the FMR1 gene and is inherited in an X-linked dominant manner.[1][2] There is no cure yet and treatment is based on the symptoms present in the person. Early physical and education therapy is recommended.[3]

Symptoms

Fragile X syndrome is characterized by developmental problems including intellectual disability and delayed speech and language development. Males are usually more severely affected than females. Additional features may include anxiety; attention deficit disorder (ADD); features of autism spectrum disorders that affect communication and social interaction; and seizures. Most males and some females with fragile X syndrome have characteristic physical features that become more apparent with age. These features may 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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Chronic otitis media
Chronic infections of the middle ear
0000389
Folate-dependent fragile site at Xq28
0003564
Intellectual disability, moderate
IQ between 34 and 49
0002342
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Macroorchidism
Large testis
0000053
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Pes planus
Flat feet
Flat foot

[ more ]

0001763
30%-79% of people have these symptoms
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Frontal bossing
0002007
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Large forehead
Increased size of forehead
0002003
Long face
Elongation of face
Increased height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth of face

[ more ]

0000276
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Muscular hypotonia
Low or weak muscle tone
0001252
Narrow face
Decreased breadth of face
Decreased width of face

[ more ]

0000275
Protruding ear
Prominent ear
Prominent ears

[ more ]

0000411
Sinusitis
Sinus inflammation
0000246
5%-29% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Ascending tubular aorta aneurysm
Bulging of wall of large artery located above heart
0004970
Autism
0000717
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Mitral valve prolapse
0001634
Seizure
0001250
Self-injurious behavior
Self-injurious behaviour
0100716
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Percent of people who have these symptoms is not available through HPO
Abnormal head movements
0002457
Coarse facial features
Coarse facial appearance
0000280
Congenital macroorchidism
0008640
Hyperactivity
More active than typical
0000752
Incomplete penetrance
0003829
Macroorchidism, postpubertal
0002050
Macrotia
Large ears
0000400
Pectus excavatum
Funnel chest
0000767
Periventricular heterotopia
0007165
Poor eye contact
0000817
Scoliosis
0002650
X-linked dominant inheritance
0001423

Cause

Mutations (changes) in the FMR1 gene cause fragile X syndrome (FXS). The FMR1 gene contains a section of DNA called a CGG triplet repeat, which normally repeats from 5 to around 40 times. In most cases of FXS, this section of DNA is repeated more than 200 times, which "turns off" the FMR1 gene and disrupts the function of the nervous system. In a small portion of cases, other types of changes in the FMR1 gene cause FXS. These changes may involve a deletion of all or part of the gene, or a change in the building blocks (amino acids) used to make the gene's protein.[4]

People with 55 to 200 repeats of the CGG segment are said to have an FMR1 premutation. Most people with a premutation are intellectually normal. In some cases, people with a premutation have lower levels of the gene's protein and may have some mild symptoms of FXS. About 20% of women with a premutation have premature ovarian failure, and some people with a premutation have an increased risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS).[4]

Diagnosis

Yes, genetic testing is available for fragile X syndromeCarrier 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.[6]

The Genetic Testing Registry (GTR) provides information about the labs that offer genetic testing for fragile X syndrome. The intended audience for the GTR is health care providers and researchers. People with questions about genetic testing should speak with a health care provider or genetics professional.

Testing Resources

  • The American College of Medical Genetics (ACMG) Laboratory Quality Assurance (Lab QA) Committee has the mission of maintaining high technical standards for the performance and interpretation of genetic tests. In part, this is accomplished by the publication of the document "ACMG Standards and Guidelines for Clinical Genetics Laboratories." These standards and guidelines are designed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. To view the Technical Standards and Guidelines for Fragile X syndrome, visit the link above.
  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no specific treatment available for fragile X syndrome. Management of this condition is generally supportive and may include:

    • recognizing the need for special education and avoiding excessive stimulation, which may help with behavioral problems
    • early educational intervention and special education that is tailored to specific learning difficulties; small class size, individual attention and avoidance of sudden change is often needed
    • medications for behavioral issues that affect social interaction
    • routine medical management of strabismus, ear infections, reflux, seizures, mitral valve prolapse, and/or high blood pressure.[3]

    Management Guidelines

    • American Academy of Pediatrics Guidelines: Health Supervision for Children with Fragile X Pediatrics 2011; 127: 994-1006.
    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Organizations Providing General Support

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • The Centers for Disease Control and Prevention (CDC) provides information on fragile X associated disorders and research. Click on the link above to visit the CDC's Fragile X Syndrome home page.
          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Fragile X syndrome. This website is maintained by the National Library of Medicine.
          • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
          • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Fragile X syndrome. Click on the link to view a sample search on this topic.

              References

              1. Fragile X syndrome. MedlinePlus. 2016; https://www.nlm.nih.gov/medlineplus/ency/article/001668.htm.
              2. Fragile X syndrome. Genetics Home Reference. April 2012; https://www.ghr.nlm.nih.gov/condition/fragile-x-syndrome.
              3. Saul RA & Tarleton JC. FMR1-Related Disorders. GeneReviews. April 26, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1384/.
              4. Fragile X syndrome. Genetics Home Reference. April 2012; https://ghr.nlm.nih.gov/condition/fragile-x-syndrome.
              5. Carriers. The National Fragile X Foundation. https://www.fragilex.org/html/carriers.htm. Accessed 3/6/2016.
              6. Robert A Saul, Jack C Tarleton. FMR1-Related Disorders. GeneReviews. October 28, 2010; https://www.ncbi.nlm.nih.gov/books/NBK1384/. Accessed 6/16/2011.
              7. Treatments. Fragile X Research Foundation of Canada. 2009; https://www.fragilexcanada.ca/index.php?home&lng=en.

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