Antenatal Diagnosis of Neuromuscular Disorders

Abstract

Despite the wide range of prenatal diagnostic protocols, the monitoring of pregnancies at risk for mendelian disorders is ideally performed on DNA of chorionic villi sampled at around 10 weeks. At present, about 100 neuromuscular diseases can be monitored using a molecular approach. Some of these diagnoses, especially those based on linkage analysis, are time consuming and require extended pedigree studies. For this reason, characterization of the family before the beginning of pregnancy is recommended. The prenatal diagnosis of spinal muscular atrophy (SMA) illustrates some of the problems encountered during these studies, including the occasional need for recovery of DNA traces of a deceased patient from Guthrie cards, frozen biopsy or microscopy glass-slides; genetic heterogeneity; high frequency of de novo gene deletions. Nevertheless, personal experience with 76 SMA prenatal diagnoses supports a high accuracy for foetal predictions. Myotonic dystrophy exemplifies another neuromuscular disorder where the continuum spectrum of clinical severity is related to the instability of a dynamic AGC triplet. The close correlation between size of expansion and clinical outcome can be used to predict age at onset and disease severity during prenatal diagnosis studies as illustrated by personal experience with 61 cases. Future development of the prenatal diagnosis of neuromuscular disorders is mainly dependent on advances in mapping and cloning of the disease genes. Another promising issue is the development of first trimester non-invasive sampling protocols, based on the recovery of foetal cells circulating in the mother or degenerating trophoblast cells shed onto the endocervix by the 6th week of gestation.