Indications for Prenatal Genetic Testing

· Maternal age:

· Individual centres should determine their own policies

· Traditionally has been offered to women >= 35 y.

· Maternal age should not be considered on its own, but rather in conjunction with other methods (ex. MSS)

· Biochemical markers (maternal serum screening)

· Computer-generated risks including biochemical markers, maternal age, gestational age, weight, and diabetes can be calculated

· If the risk exceeds the chosen cutoff value, amniocentesis can be offered

· Cutoff is commonly chosen to be the age-related risk of a 35 y. mother (1 in 385 at term, 1 in 270 in the mid-second trimester)

· Different programs may choose different cutoffs

· Pregnancy history

· Previous abortus, stillbirth, or livebirth with a chromosomal abnormality

· Parent with a (potentially transmissible) chromosomal abnormality

· UPD testing for Robertsonian translocations or supernumerary markers involving appropriate chromosomes

· Relative with an offspring with a chromosomal abnormality other than offspring with Down syndrome

· For trisomy type Down syndrome, those with 2 or more affected relatives should be considered for prenatal testing

· Parent with an X-linked disorder

· Carriers and affected individuals

· Biochemical or molecular testing for the disorder, or fetal sexing where no specific test is available

· Family history of fragile X syndrome

· Molecular testing is available

· Family history of chromosomal breakage syndromes

· FA, Bloom, AT, XP, Roberts

· Exposure of father to therapeutic radiation in the past

· ICSI pregnancy

· Sex chromosome abnormalities in ~1%

· Family history of microdeletion / microduplication syndrome

· Genetic counseling recommended and prenatal testing offered to all at-risk individuals

· Abnormal U/S

· Major fetal anomalies – testing is indicated

· Multiple congenital anomalies

· Neural tube defects

· Cystic hygroma

· Limb abnormalities

· Omphalocele

· Duodenal stenosis / atresia

· Significant ventriculomegaly

· Significant facial abnormalities

· IUGR

· Variation in amniotic fluid volume

· FISH for 22q11.2 is indicated for any cardiac abnormality, particularly conotruncal defects

· Minor fetal anomalies (“soft signs”) – no specific recommendations; more studies are necessary

· Down:

· Increased nuchal thickening

· Renal pyelectasis

· Shortened femurs

· Echogenic bowel

· Echogenic foci of the left ventricle

· Increased fetal iliac angle

· Hypoplasia of the middle phalanx of the fifth digit

· Trisomy 18:

· Choroid plexus cysts

· Family history of neural tube defect (NTD)

· First investigation should be MSAFP + U/S

· Amniocentesis should be considered in mother with increased risk with unreliable U/S examination

· Elevated MSAFP

· Amniocentesis should be considered in mother with increased risk with unreliable U/S examination

· Parents are carriers of a genetic disease

· Tay-Sachs

· Hemoglobinopathies

· Cystic fibrosis

References:

· Canadian Guidelines for Prenatal Diagnosis: Genetic Indications for Prenatal Diagnosis. J Society of Obtetricians and Gynecologists of Canada (2001):105.