A new gene has been identified that leads to a form of CMD that shares similarities with collagen VI CMD subtype (Ullrich/Bethlem).
What is the gene?
The gene is called integrin alpha 9. It maps to the following genetic location, 3p23-21.
How does an integrin alpha 9 mutation affect people?
- Finger, wrist and toe hyperlaxity: this means extremely flexible fingers and wrists that are commonly referred to as “double jointed”
- Ankle, knee and shoulder contractures: stiffness in these joints with decreased flexibility
- Hyotonia, muscle weakness at birth with contractures
- Generalized slowly progressive muscle weakness over time
- Intelligence is normal
- CPK (creatine phosphokinase) levels are normal to mildly elevated (17-959 U/l)
- Lung capacity is diminished on average by 50%, but seemingly stable over long periods of time. Most people do not develop respiratory failure in spite of diminished lung capacity.
- All cases described were able to walk many through adulthood. Some people with integrin alpha 9 mutations lost this ability and became wheelchair dependent.
- Scoliosis, no rigid spine
Some of these features are similar to findings in the collagen VI CMD subtype. Distinguishing features from the collagen VI subtype include the absence of:
- a high arched palate
- torticollis (stiff neck)
- skin textural changes
- prominent calcaneus (heel bone)
This form of CMD was first described by Dr. Tetreault and Dr. Brais in a medical article entitled “A new form of CMD with joint hyperlaxity maps to 3p23-21”, published in Brain, 2006. This form of CMD is described in the French Canadian population. Given the results of genetic linkage analysis, there is a likely founder mutation in the French Canadian population which accounts for the frequency of this disease within a regional area of the Province of Quebec, Canada. In all cases, collagen VI genes were tested and no genetic mutation was found.
Tetreault M, Duquette A, Brais B, et al. A new form of congenital muscular dystrophy with joint hyperlaxity maps to 3p23-21. Brain Aug 2006; 129(Pt8):2077-84.