Last update: 12/12/2007

Background to disease

OMIM #602668 (gene OMIM #116995)

Myotonic Dystrophy 2 (DM2) is also known as proximal myotonic myopathy (PROMM). Clinically the phenotype is very similar to DM1 (see description on separate page) except there is no brain involvement, only degenerative changes; myotonia, myalgia. There is no congenital or juvenile form of DM2 and only 2% of muscle fibres are dystrophic on histological examination. However, occasionally DM2 is associated with sudden death due to cardiomyopathy.

As with DM1 it is inherited in an autosomal dominant fashion.

The disease is due to an expanded CCTG repeat within a partially interrupted, polymorphic (TG)_n(TCTG)_k(CCTG)_l element, known as CL3N58. The element is within intron 1 of the znf9 gene at 3q21, which codes for an RNA-binding protein expressed in skeletal and cardiac muscle. As with DM1 the element is transcribed into RNA but not into protein. Expanded, pathogenic allele sizes range from 75 to approximately 11,000 CCTG repeats. Due to the phenotypic overlap between DM1 and DM2 but lack of genotypic overlap, it has been determined that RNA toxicity plays a role in both disorders. Over-expression of CUG, CCUG, CUG-BP or depletion of muscleblind proteins results in splicing alterations resulting in the downstream characteristics of both types of DM.

Laboratory Analysis

Analysis for this disease is now carried out by the Northern Genetics Laboratories under a reciprocal arrangement (GENLYNC). Please contact them directly regarding information regarding turnaround time and sensitivity. Local samples should still be sent via the Yorkshire Regional Genetic Laboratory where they will be forwarded as whole blood as appropriate. DNA from these samples can be stored in the Yorkshire Regional Genetic Laboratory if it is anticipated that future tests may be required (please indicate clearly on referral card if required).