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June 2009

Preconception Carrier Screening and Testing for Genetic Disorders

Mari-Paule Thiet, M.D.
Perinatologist and Chief of Obstetrics
Director, UCSF Prenatal Diagnosis Center

Sherri Pena, M.S.
Genetic Counselor and Pactice Manager
UCSF Prenatal Diagnostic Center

Katherine Rauen, M.D., Ph.D.
Medical Geneticist
UCSF Prenatal Diagnostic Center

While most women give birth to healthy babies, about 3 percent of newborns have a major birth defect. Preconception screening and testing with a simple blood test can help a couple decide whether or not to have children and allow them to consider all of their reproductive options. It also greatly minimizes the potential risks, some of them life-threatening, to a mother and fetus.

As a result of carrier screening programs, the incidence of inherited conditions, such as Tay-Sachs disease (TSD), has decreased by more than 90 percent.

Since many individuals who are carriers of genetic disorders don't have symptoms, primary care physicians can play an important role in determining if carrier screening and testing are appropriate. The American College of Obstetrics and Gynecology (ACOG) recommends the following screening guidelines.

Screening for Fragile X Syndrome

Fragile X syndrome is the most common inherited form of mental retardation, affecting about 1 in 3,600 males and 1 in 6,000 females. Mental retardation ranges in severity, although most patients have a moderate degree of retardation. One in 250 women is a carrier of fragile X syndrome, regardless of ethnicity, and many children with the disorder are not diagnosed until 3 or 4 years of age, after many of their parents have had another child.

Fragile X syndrome is caused by expansion of the repeated trinucleotide segment of DNA that leads to altered transcription of the fragile X mental retardation 1 (FMR1) gene.

ACOG recommends the following for individuals considering pregnancy:

  • Patients with a family history of mental retardation or fragile X syndrome should consider genetic counseling and be offered genetic testing to assess the risk of having an affected child.

  • If a woman has ovarian failure or elevated follicle-stimulating hormone level before the age of 40 without a known cause, fragile X carrier screening should be considered to determine if she has a premutation.

Additional testing guidelines are recommended for women at risk who are already pregnant and for children who may show signs of fragile X syndrome.

Regardless of family history, any woman who asks for fragile X syndrome testing should be offered the service.

Cystic Fibrosis Screening

ACOG and the American College of Medical Genetics (ACMG) recommends that cystic fibrosis screening is offered to all couples, who are planning pregnancy or seeking prenatal care, in which both partners are of Caucasian, European or Ashkenazi Jewish ethnicity.

Cystic fibrosis is more common in Caucasians, including Ashkenazi Jews, than in other populations and screening detects a higher percentage of carriers in this population than in others. However, it is reasonable to offer cystic fibrosis screening to all couples, regardless of race or ethnicity.

Other recommendations for preconception screening for cystic fibrosis include:

  • For patients with a family history of cystic fibrosis, medical records should be obtained to identify the gene mutation — cystic fibrosis transmembrane conductance regulator (CFTR) — in the affected family members. If the mutation has not been identified, screening with an expanded panel of mutations or in some cases complete analysis of the CFTR gene by sequencing may be performed. Patients may benefit from genetic counseling.

  • Patients with partners with cystic fibrosis or congenital bilateral absence of the vas deferens may benefit from screening with an expanded panel of mutations or in some cases a complete analysis of the CFTR gene by sequencing.

  • When both partners are cystic fibrosis carriers, genetic counseling is recommended to review prenatal testing and options.

  • Screening may identify individuals, who have not been diagnosed with cystic fibrosis but who have two cystic fibrosis mutations. These individuals may have a milder form of the condition and should be referred to a cystic fibrosis specialist for further evaluation and genetic counseling.

Patients of Eastern European Jewish Descent

Carrier screening for specific genetic conditions often is determined by an individual's ancestry. Certain autosomal recessive disorders — many that are lethal in childhood and associated with significant morbidity — are more prevalent in people of Eastern European Jewish (Ashkenazi) descent. ACOG recommends that this population is offered carrier screening for certain disorders before conception or during early pregnancy so that a couple has an opportunity to consider prenatal diagnostic testing.

First, the family history of individuals considering pregnancy should be recorded to determine if either member of the couple is of Eastern European Jewish ancestry or has a relative with one or more of the following genetic conditions — Tay-Sachs disease (TSD), Canavan disease, cystic fibrosis, familial dysautonomia, mucolipidosis IV, Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome and Gaucher's disease.

This population should then be screened for the following:

  • Canavan disease
  • Cystic fibrosis
  • Familial dysautonomia
  • Tay-Sachs disease (TSD)

Patients also may inquire about screening for other disorders, such as:

  • Bloom syndrome
  • Fanconi anemia group C
  • Gaucher's disease
  • Mucolipidosis IV
  • Niemann-Pick disease type A

UCSF Prenatal Diagnosis Center

The UCSF Prenatal Diagnosis Center offers comprehensive genetic counseling, screening and diagnostic testing for genetic conditions such as Canavan disease, cystic fibrosis, Down syndrome, fragile X syndrome, sickle cell anemia, Tay Sachs disease and thalassemia.

Patients have access to the most advanced technology, including:

  • Carrier testing
  • Chorionic villus sampling (CVS)
  • Nuchal translucency (NT) screening

Patients can participate in research on new, less invasive methods for screening and diagnosis.

For help in referring patients, call the Prenatal Diagnostic Center at (415) 476-4080 and ask to speak with a genetic counsellor.

For more information, contact the Physician Referral Service at UCSF Medical Center,:

Phone(800) 444-2559
Email referral.center@ucsfmedctr.org

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