SMA Can Be X-Linked

MDA grantee Lisa Baumbach-Reardon at the University of Miami’s Miller School of Medicine, with colleagues in the United States, Spain and Germany, can now say with assurance that there is an X-linked form of spinal muscular atrophy (SMA) that resembles the most severe (type 1) chromosome 5 form. X-linked diseases generally affect only males, but females can be carriers.

In the January issue of Genetics in Medicine, the investigators describe eight families (one previously analyzed and the other seven new to this study) with an X-linked disease affecting only male infants and involving severe loss of muscle tone, as well as multiple contractures (frozen joints) and/or bone fractures, and death within the first two years of life in 75 percent of cases.

The investigators note that an X-linked disease resembling severe infantile SMA was first described in 1938, but the disorder has been presumed rare. Now, they say, their new findings, coupled with the approximately 4 percent of SMA patients who don’t appear to have SMN1 mutations, may mean that X-linked SMA isn’t as rare as has been presumed.

They’ve determined that X-linked SMA, like its chromosome 5 counterpart, is primarily a disease involving loss of lower motor neurons. Finding another SMA gene, they say, “will provide major insights ... into the etiology [origin] and developmental timing of motor neuron loss,” with implications for all types of SMA.