Variable Manifestation of Dystrophic Curschmann-Steinert Myotonia as a Result of Genomic Imprinting

Overview

Myotonic dystrophy is an autosomal dominant disorder characterized by myotonia, muscular weakness, cataracts, heart blocks or arrythmia with ECG changes and population incidence 1:8000. Heterozygotic mutation of DMPK gene on chromosome 19 is characterized by expansion of trinucleotide CTG repeats and the severity varies with the number of repeats, mildly affected person having from 50 to 80, severely affected patients over 2000 CTG triplets. Direct molecular genetic diagnosis is therefore unproblematic. Nevertheless this affection is underdiagnosed due to very variable clinical manifestation depending on the number of repeats (premutation and full mutation) and sex of parent, from whom is the mutation inherited - effect of genomic imprinting.

Authors refer to the family, which was recommended for genetic care after the perinatal death of two children due to respiratory distress syndrome. The etiology of the infertility was elucidated in familiar occurrence of myotonic dystrophy. In future reproduction of the family early prenatal diagnosis of causal mutation could be offered.

Key words:
myotonic dystrophy, trinucleotide repeats expansion, autosomal dominant inheritance, respiratory distress syndrome, variability of expression, genomic imprinting