Fragile X Syndrome

What is UNITY Fetal Risk™ Screen for fragile X syndrome ?

UNITY Fetal Risk Screen starts with carrier screening for fragile X syndrome (FXS) to identify premutation carriers who have an increased risk of having a baby with FXS. If you are a premutation carrier, UNITY Fetal Risk Screen will automatically determine the sex of your baby and AGG interruption analysis, as described below. These pieces of information help to predict disease risk and severity. While not diagnostic, UNITY Fetal Risk Screen offers early identification of pregnancies at increased-risk for FXS, which is crucial for informed family planning and early intervention.

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The American College of Obstetricians and Gynecologists recommends fragile X syndrome carrier screening for individuals planning to start a family or those already pregnant that have a personal or family history of unexplained autism, intellectual disability, unexplained ovarian insufficiency, fragile X syndrome or fragile X-related disorders

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What is Fragile X syndrome?

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability. The type and severity of symptoms depend on the age and sex of the individual. Males typically have more severe symptoms than females. Male children with FXS are at risk for moderate to severe intellectual disability, low muscle tone, seizures, scoliosis (curving of the spine), flat feet, and recurrent ear infections. Typically, a child with FXS grows as expected, but often has a larger than average head size. Developmental delay is commonly noticeable in the first couple years of life.

Behaviors associated with FXS include ADHD, hand-flapping movement, poor eye contact, self-injury behaviors, anxiety, and shyness. Autism spectrum disorder is diagnosed in over half of individuals with FXS. Females diagnosed with FXS generally do not have the physical features that are associated with males. About half of affected females will have symptoms of FXS, such as mild/moderate intellectual disability, anxiety, and mild/moderate learning challenges.

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How is Fragile X syndrome inherited? 

Fragile X syndrome (FXS) is an X-linked condition. Typically, males have XY chromosomes and females have XX chromosomes. FXS is caused by a mutation in the FMR1 gene, which is located on the X chromosome. The FMR1 gene contains a segment of DNA sequence (CGG) that is normally repeated up to 55 times. Those with expanded CGG repeat lengths of 55-200 are considered “premutation carriers” for FXS. CGG repeat lengths of 200+ are considered a “full mutation” that causes fragile X syndrome.

If a person is a premutation carrier for FXS, there is a 50% chance for their offspring to inherit a FMR1 gene with a CGG repeat variant - repeat lengths can increase in future generations to cause a full FXS mutation in offspring. This chance for expansion to a full FXS mutation in offspring is dependent on different factors, including the parent’s CGG repeat number and presence of a unique DNA sequence (AGG) interruption in the FMR1 gene. Males with a full FXS mutation are often more severely affected than females with a full FXS mutation. Premutation carriers for FXS may be at increased risk for different health conditions, including premature ovarian failure and ataxia. 

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Who should consider fragile X syndrome screening? 

Carrier screening for fragile X syndrome should be considered if a person has a personal or family history of unexplained autism, intellectual disabilities, ovarian insufficiency, fragile X syndrome and/or fragile X-related disorders If you are found to be a premuation carrier, your provider will discuss additional diagnostic testing that can be done either before or after delivery.

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UNITY Fetal Risk Screen Workflow for fragile X syndrome

Test as early as 9 weeks
Your blood sample can be collected in the doctor’s office, at a local lab, or through our mobile services. Your blood sample is shipped to our CAP/CLIA certified laboratory in northern California.

UNITY Aneuploidy™  Screen + UNITY Fetal RhD™  and Fetal Antigen™  results as early as 10 weeks

Within about one week from lab receipt, your doctor will receive the baby’s risk score for aneuploidies (chromosome conditions) and fetal RhD and fetal antigens (if added). You will receive a text or email indicating your results are available on our portal, or your healthcare provider may call you with the results.

Carrier status + fetal risk assessment results as early as week 11
Within about two weeks from lab receipt, your doctor will receive the results of your maternal carrier status testing. If you were found to be a carrier for any X-linked condition tested, UNITY Fetal Risk Screen will automatically determine the sex of your baby to provide further clarity in their chances of being affected with that condition. You will receive a text or email indicating your results are available on our portal, or your healthcare provider may call you with the results.

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What do fragile X syndrome screening results mean?

Your UNITY Fetal Risk Screen results will tell you if you are a carrier for fragile X syndrome, or other conditions. Then, if you are currently pregnant and a premutation carrier for fragile X syndrome, UNITY Fetal Risk Screen will determine the sex of your baby and number of AGG interruptions to help predict disease risk and severity. If you are a FXS premutation carrier, fetal risk will be reported as either “increased risk” or “high risk” based on the sex of your baby and the number of AGG interruptions you have. Your report will have specific information about your results.  

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UNITY Fetal Risk Screen results are not diagnostic, so there is always the option for additional confirmatory testing to be performed to understand more about fetal FXS risk. There are options both before and after delivery. 

• Before Birth:
  Testing during pregnancy can be performed by obtaining a sample of placenta (chorionic villus sampling or CVS) or fluid around your baby (amniocentesis) which both contain DNA that is representative of your baby.  A CVS is ideally performed between 10 to 13 weeks in pregnancy while an amniocentesis is typically performed between 15 to 24 weeks in pregnancy.  Both procedures are generally safe, but have a small risk for pregnancy complications, including miscarriage.

• After Birth: 
  Testing for your baby can be performed after birth through a blood test as a newborn or with your baby’s pediatrician.

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Frequently asked questions

Is there a cure for fragile X syndrome?

Currently, there is no cure for fragile X syndrome, but there are treatments that help minimize the symptoms of fragile X syndrome. Ongoing research includes clinical trials and discovery of new medications to manage symptoms. 

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What are the treatment options for fragile X syndrome?

Treatment for fragile X focuses on managing symptoms and improving quality of life. Individuals with FXS typically benefit from early intervention, individualized education support, and psychopharmacologic treatment of symptoms in conjunction with different therapies, including speech and language, occupational, and behavioral therapies. 

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As a carrier for fragile X syndrome, am I at increased risk for health concerns?

Around 20% of female FXS premutation carriers experience premature ovarian insufficiency (FXPOI). This can cause menopausal-type symptoms and infertility. Both male and female FXS premutation carriers are at increased risk for ataxia, which impacts balance, fine motor skills and speech, and tremors. Male premutation carriers have a higher chance to experience these symptoms and the risk is dependent on CCG repeat lengths. All premutation carriers for FXS should discuss these risks with their primary care provider to be screened and managed appropriately. 

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Treatment & Resources Callouts

• National Fragile X Foundation
• CDC: Fragile X Syndrome Information