Paternal transmission of congenital myotonic dystrophy.

Abstract

We report a rare case of paternally transmitted congenital myotonic dystrophy (DM). The proband is a 23 year old, mentally retarded male who suffers severe muscular weakness. He presented with respiratory and feeding difficulties at birth. His two sibs suffer from childhood onset DM. Their late father had the adult type of DM, with onset around 30 years. Only six other cases of paternal transmission of congenital DM have been reported recently. We review the sex related effects on transmission of congenital DM. Decreased fertility of males with adult onset DM and contraction of the repeat upon male transmission contribute to the almost absent occurrence of paternal transmission of congenital DM. Also the fathers of the reported congenitally affected children showed, on average, shorter CTG repeat lengths and hence less severe clinical symptoms than the mothers of children with congenital DM.We conclude that paternal transmission of congenital DM is rare and preferentially occurs with onset of DM past 30 years in the father.

Congenital Myotonic Dystrophy: Canadian Population-Based Surveillance Study

“…1 This seems a high number given that most affected parents, almost exclusively mothers, of children will themselves have expansions between 500-1500 repeats, which is usually associated with a moderate clinical phenotype. 11 Rare cases of paternal transmission causing CDM have been reported, 12,13 and 1 of the children in this study had an affected father. Given that the majority of cases are index cases, the use of the repeat size in either the mother or the CDM child cannot routinely be used for prognostication.…”

The myotonic dystrophies: diagnosis and management

“…Large CTG expansions are possibly toxic or negatively select against sperm compared with oocytes with larger expansions. To confuse the issue further, anticipation may be seen in patients with DM1 who inherit a smaller expanded CTG repeat from their father and expansions in these individuals tend to be greater than from mothers with a similar repeat size 11 12. The severity of anticipation is therefore dependent on the size of the repeat and the sex of the parent the expanded repeat is inherited from 13…”

Molecular Genetics and Genetic Testing in Myotonic Dystrophy Type 1

“…The largest expansions, associated with congenital form of disease, are almost exclusively maternally transmitted [40, 45], though a few cases of paternally transmitted congenital form have been reported [54, 55]. Mothers of congenital offspring have an expanded allele size significantly greater than mothers of noncongenital offspring (mean size ~600 repeats versus ~250 repeats, resp.)…”