Fragile X syndrome

Answer 1

Definition

Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females.

Alternative Names

Martin-Bell syndrome; Marker X syndrome

Causes, incidence, and risk factors

Fragile X syndrome is caused by a change in the FMR1 gene. A small section of the gene code (three letters only -- CGG) is repeated on a fragile area of the X chromosome. The more repeats, the more likely there is to be a problem.

Normally, the FMR1 gene makes a protein needed for your brain to grow properly. A defect in this 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 is likely to affect them more severely. You can have Fragile X syndrome even if your parents do not have it.

Fragile X syndrome can be a cause of autism or related disorders, although not all children with fragile X syndrome have these conditions.

SymptomsBehavior problems associated with fragile X syndrome include:

• Delay in crawling, walking, or twisting
• Hand clapping or hand biting
• Hyperactive or impulsive behavior
• Mental retardation
• Speech and language delay
• Tendency to avoid eye contact

Physical signs may include:

• Flat feet
• Flexible joins 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 mental retardation, but may have other problems. Women with less severe changes may have premature menopause or difficulty becoming pregnant. Both men and women may have problems with tremors and poor coordination.

Signs and tests

The person will have a family history of Fragile X syndrome (especially a male relative).

There are very few outward signs of Fragile X syndrome in babies. Some signs may include:

• Large head circumference in babies
• Mental retardation
• Oversized testes (macro-orchidism) in males who have reached puberty
• Subtle differences in facial characteristics

In females, excess shyness may be the only sign of the problem.

A genetic test called polymerase chain reaction (PCR) is used to diagnose this disease. This test looks for a mutation (called a triplet repeat) in the FMR1 gene.

In the past, a specific type of chromosome analysis was done. Such testing may still be available.

Treatment

There is no specific treatment for Fragile X syndrome. Instead, training and education help affected children function at as high a level as possible. Because the condition is not rare, educational approaches have been developed and tested.

Support Groups

National Fragile X Foundation -- www.nfxf.org

Expectations (prognosis)

The outcome depends on the extent of intellectual impairment that is present as well as emotional and social skills.

Complications

Complications vary depending on the type and severity of symptoms.

• Recurrent infections in children
• Seizure disorder

Calling your health care provider

Call your health care provider if you suspect Fragile X syndrome in a child with mental retardation. Genetic counseling is recommended to help families understand the condition, and to understand the complex nature of DNA testing in Fragile X.

Prevention

Genetic counseling may help both existing and prospective parents with a family history of Fragile X syndrome, or a family history of other symptoms such as tremor. Genetic testing can help determine the level of risk in these families.

Accurate diagnosis is important, because other family members can inherit Fragile X syndrome or other problems related to an increased number of repeats in FMR1.

ReferencesWise PH. Developmental disabilities and chronic illness. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds.Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 38.

Answer 2

Definition

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 (mental retardation) in boys.

Alternative Names

Martin-Bell syndrome; Marker X syndrome

Causes, incidence, and risk factors

Fragile X syndrome is caused by a change in a gene called FMR1. A small part of the gene code is repeated on a fragile area of the X chromosome. The more repeats, the more likely there is to be a problem

The FMR1 gene makes a protein needed for your brain to grow 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 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.

SymptomsBehavior problems associated with fragile X syndrome include:

• Delay in crawling, walking, or twisting
• Hand clapping or hand biting
• Hyperactive or impulsive behavior
• Mental retardation
• 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 mental retardation, but may have other problems. Women with less severe changes may have premature menopause or difficulty becoming pregnant. Both men and women may have problems with tremors and poor coordination.

Signs and tests

There are very few outward signs of Fragile X syndrome in babies. Some signs may include:

• Large head circumference in babies
• Mental retardation
• 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.

Treatment

There is no specific treatment for Fragile X syndrome. Instead, training and education have been developed to help affected children function at as high a level as possible.

Support Groups

National Fragile X Foundation -- www.fragilex.org

Expectations (prognosis)

How well the patient does depends on the amount of intellectual disability (mental retardation).

Complications

Complications vary depending on the type and severity of symptoms.

• Recurrent 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.

Prevention

Genetic counseling may be helpful if you have a family history of this syndrome and are planning to become pregnant.

References

Shapiro BK, Batshaw ML. Intellectual disability. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 33.

Reviewed By

Review Date: 09/06/2011

A.D.A.M. Editorial Team: David Zieve, MD, MHA, and David R. Eltz. Previously reviewed by Chad Haldeman-Englert, MD, Wake Forest School of Medicine, Department of Pediatrics, Section on Medical Genetics, Winston-Salem, NC. Review provided by VeriMed Healthcare Network (8/4/2011).