Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counselling in DM1 families

Abstract

Objectives: To analyse the results obtained from prenatal diagnoses in myotonic dystrophy type 1 (DM1) performed in our hospitals during the last 13 years.

Methods: Molecular analyses were conducted on chorionic villi or cultured amniotic fluid samples obtained for prenatal diagnosis of DM1. CTG expansion was analyzed by polymerase chain reaction (PCR) and Southern blot techniques.

Results: From 154 prenatal diagnoses performed in 13 years, 51% were found to be healthy and 49% affected. Considering the 75 carriers of the mutation, in 65.3% of the cases, the mother was the transmitting parent versus 36.5% of fathers. From these female transmissions, 31/49 foetuses had expansion in the neonatal form range, namely, congenital myotonic dystrophy (CMD).

Conclusions: In our series, no significant deviation of the 50% expected frequency of transmission in autosomal dominant disorder was seen. We show that when the disease is transmitted by a male, the mean intergenerational variation is minimal (mean = 56 CTG, SD = 177 CTG). However, this does not occur in the affected mothers, where the mean intergenerational expansion is very high (mean = 948 CTG, SD = 815 CTG) and the difference is statistically significant (t-Student p < 0.0001). Our data have important implications for the genetic counselling of DM1 families.