Fragile X syndromeMartin-Bell syndrome; Marker X syndrome
Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited intellectual disability in boys.
Fragile X syndrome is caused by a change in a gene called FMR1. A small part of the gene code is repeated several times in one area of the X chromosome. The more repeats, the more likely the condition will occur.
The FMR1 gene makes a protein needed for your brain to function properly. A defect in the gene makes your body produce too little of the protein, or none at all.
Boys and girls can both be affected, but because boys have only one X chromosome, a single fragile X expansion is likely to affect them more severely. You can have fragile X syndrome even if your parents do not have it.
A family history of fragile X syndrome, developmental problems, or intellectual disability may not be present.
Behavior problems associated with fragile X syndrome include:
- Autism spectrum disorder
- Delay in crawling, walking, or twisting
- Hand flapping or hand biting
- Hyperactive or impulsive behavior
- Speech and language delay
- Tendency to avoid eye contact
Physical signs may include:
- Flat feet
- Flexible joints and low muscle tone
- Large body size
- Large forehead or ears with a prominent jaw
- Long face
- Soft skin
Some of these problems are present at birth, while others may not develop until after puberty.
Family members who have fewer repeats in the FMR1 gene may not have intellectual disability. Women may have premature menopause or difficulty becoming pregnant. Both men and women may have problems with tremors and poor coordination.
Exams and Tests
There are very few outward signs of fragile X syndrome in babies. Some things the health care provider may look for include:
- Large head circumference in babies
- Intellectual disability
- Large testicles after the start of puberty
- Subtle differences in face features
In females, excess shyness may be the only sign of the disorder.
Genetic testing can diagnose this disease.
There is no specific treatment for fragile X syndrome. Instead, training and education have been developed to help affected children function at the highest possible level. Clinical trials are ongoing (www.clinicaltrials.gov) and looking at several possible medicines for treating fragile X syndrome.
National Fragile X Foundation: fragilex.org
How well the person does depends on the amount of intellectual disability.
Complications vary, depending on the type and severity of symptoms. They may include:
- Recurrent ear infections in children
- Seizure disorder
Fragile X syndrome can be a cause of autism or related disorders, although not all children with fragile X syndrome have these conditions.
Genetic counseling may be helpful if you have a family history of this syndrome. All pregnant women and those planning a pregnancy should be offered genetic screening for these conditions.
Gregg AR, Aarabi M; ACMG Professional Practice and Guidelines Committee, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. Seattle, WA: University of Washington, Seattle; 2021;23(10):1793-1806. PMID: 34285390 pubmed.ncbi.nlm.nih.gov/34285390/.
Hunter JE, Berry-Kravis E, Hipp H, Todd PK. FMR1 disorders. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2022. PMID: 20301558 pubmed.ncbi.nlm.nih.gov/20301558/. Updated November 21, 2019.
Kumar V, Abbas AK, Aster JC. Genetic and pediatric diseases. In: Kumar V, Abbas AK, Aster JC, eds. Robbins Basic Pathology. 10th ed. Philadelphia, PA: Elsevier; 2018:chap 7.
Madan-Khetarpal S, Arnold G, Ortiz D. Genetic disorders and dysmorphic conditions. In: Zitelli BJ, McIntire SC, Nowalk AJ, Garrison J, eds. Zitelli and Davis' Atlas of Pediatric Physical Diagnosis. 8th ed. Philadelphia, PA: Elsevier; 2023:chap 1.