As of 20 17, these include Bloom syndrome, familial hyperinsulinism, Fanconi anemia, Gaucher disease, glycogen storage disease type I (von Gierke disease), Joubert syndrome, maple syrup urine disease, mucolipidosis type IV, Niemann-Pick disease, and Usher syndrome. Gaucher disease difers from the other conditions listed in that it is has a wide range in phenotype-from childhood illness to absence of symptoms throughout life. Also, efective treatment is available in the form of enzyme therapy.
Diagnostic procedures used in prenatal diagnosis include amniocentesis, chorionic villus sampling (CVS), and rarely fetal blood sampling. hese enable characterization of an increasingly large number of genetic abnormalities before birth. Karyotype analysis has a diagnostic accuracy of more than 99 percent for aneuploidy and chromosomal abnormalities larger than 5 to 10 megabases. In the setting of a fetal structural abnormality, chromosomal microarray analysis (CMA) is recommended as the first-line genetic test performed, as it may detect clinically significant chromosomal abnormalities in approximately 6 percent of fetuses with normal standard karyotype (Callaway, 2013; de Wit, 2014). An exception would be if the structural abnormality strongly suggests a particular karyotype-such as endocardial cushion defect with trisomy 21 or holoprosencephaly with trisomy 13. In such cases, karyotyping with or without luorescence in-situ hybridization (FISH) may be ofered as the initial test (American College of Obstetricians and Gynecologists, 2016b). Among those without evidence of a fetal structural abnormality and with a normal karyotype, CMA has detected additional chromosomal abnormalities (pathogenic copy number variants) in approximately 1 percent. It is therefore made available whenever a prenatal diagnostic procedure is performed (American College of Obstetricians and Gynecologists, 2016b; Callaway, 2013). Types of CMA platforms and their benefits and limitations are reviewed in Chapter 13 (p. 271).
Ironically, improvements in aneuploidy screening tests, in particular the widespread use of cell-free DNA screening, have resulted in a dramatic drop in the number of prenatal diagnostic procedures. Larion and colleagues (2014) reported a 70-percent decline in CVS procedures and a nearly 50-percent drop in amniocentesis procedures following introduction of cell-free DNA screening in 2012. This urther amplified the decrease in amniocentesis procedures that began following adoption of first-trimester screening (Warso, 2015). In addition, because so many disorders can be diagnosed from amnionic fluid specimens, fetal blood sampling is now rarely, if ever, indicated for genetic diagnoses.