Myotonic Dystrophy Type 2, DM2 - ZNF9 (CNBP)

Klinische Symptomatik

Myotonic Dystrophy Type 2 (DM2) is a multisystem disorder with an onset often in young adulthood. It is characterized by a proximal, rather than distal, muscular dystrophy, a delayed muscular relaxation (myotonia) and muscle pain; facial muscles are spared. Non neuromuscular features are cataract, hypognadism and cardial involvement (mainly arrhythmia and conduction defects). In contrast to DM1 the clinical manifestations in DM2 are milder without mental impairment and a congenital form.

Genetik

Myotonic Dystrophy Type 2 is an autosomal dominant condition. It is caused by an expansion of a CCTG tetranucleotide repeat in exon 1 of ZNF9 (CNBP, chromosome 3q21.3).

 

	Tetranucleotide repeats
Normal allele	up to 26
Pathological allele	75 - 11000

 

The wildtype gene shows a complex repeat motive (TG)n(TCTG)n(CCTG)n, which varies from 104 to 176bp in length. Patients carry a (CCTG)n expansion of 75 to 11.000 (mean 5000) CCTG-repeats. The clinical course of the disease is not dependable on the size of the expansion. Similar to DM1 there is an anticipation seen in DM2. There may be an earlier onset and more severe symptoms in off-spring, especially by inheritance through the paternal germline.

Häufigkeit

approx. 1 : 20 000 in Germany

 

Diagnostik