Abstract
Myotonic dystrophy has been shown to be caused by an expansion of a CTG repeat in the 3' untranslated region of the myotonin-protein kinase gene (DMPK). Congenital myotonic dystrophy (CDM) is the most severe phenotype and is characterized by marked hypotonia, and facial weakness at birth. Respiratory distress is also common. Individuals with CDM tend to have larger numbers of CTG repeats than individuals with the other forms of DM, with sizes ranging from 700 to >2000 repeats; however, there is considerable overlap and not all individuals with large repeats have CDM. Most cases of CDM are maternally inherited and the likelihood of having a second child affected with CDM has been estimated to be 90-100% if the expanded allele is passed on. We report a baby, born after a sibling with CDM, who does not have symptoms of congenital myotonic dystrophy despite having 1000 CTG repeats.
At delivery the proband was extremely floppy and required intubation due to respiratory distress. He remained ventilator-dependant and died 40 days later. The pregnancy had been complicated by polyhydraminos. Southern blot analysis showed that he had a smear of DMPK CTG repeats ranging in size between 1700 and 2300. The mother had grip myotonia and a typical myotonic facies. Molecular analysis revealed a repeat size of 600. Her then 6 year old daughter who had signs consistent with childhood, onset DM was found to have 1300 CTG repeats. Prenatal diagnosis was offered for a subsequent pregnancy. Analysis of CVS revealed an expansion of 1000 repeats in the fetus. Sizing was repeated on aminocytes with the same result. As an expansion of this size is within the range found in CDM and as the mother had had a previous affected child, the likelihood that this fetus would have CDM was considered high. The mother decided to continue with the pregnancy and was induced at 39 weeks gestation after a normal pregnancy. The baby had no evidence of CDM. The neonatal reflexes were normal and there was no respiratory distress. Analysis of DNA from cord blood confirmed the results obtained for both CVS and ammocytes.
This case illustrates that a fetus with a large CTG expansion in the CDM range, will not necessarily present with CDM despite having had a sibling with CDM.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carson, N., Whelan, D. & Zeesman, S. Absence of congemla1 myotomc dystrophy (CDM) in a baby wth 1000 DMPK CTG repeats born afler a slblmg with CDM. Genet Med 2, 62 (2000). https://doi.org/10.1097/00125817-200001000-00051
Issue Date:
DOI: https://doi.org/10.1097/00125817-200001000-00051