What is SMA?

Information for physicians

Spinal Muscular Atrophy (SMA) - the most common inherited lethal disorder of infants.

Spinal muscular atrophy (SMA) is a degenerative neuromuscular disease with an incidence of 1:10.000 (Orphanet). This rare condition is the most common inherited lethal disorder of infants (Arnold D et al). The autosomal recessive mutation usually affects the survival motor neuron (SMN) 1 gene on chromosome 5q13 (Melkie J et al). In only 5% of affected persons rare mutations are responsible and in further 2% a de novo mutation are present. Furthermore, there are also non-5q SMA cases (Lefebvre S et al).

Figure 1: Autosomal recessive inheritance of SMA

Parents who are carriers for the faulty SMN1 gene do not have clinical symptoms.
Green: faulty SMN1 gene, Grey: normal SMN1 gene

Frequencies of SMA carriers are about 1 in 37 to 1 in 125 depending on ethnic background (Hendrickson B et al). In case of both parents carrying one faulty SMN1 gene, 25% of their offspring will be healthy, 50% will be carriers and 25% of infants will be affected by SMA (Figure 1).

Consequences of faulty SMN1 genes

Faulty survival motor neuron (SMN) 1 genes leads to a lack of functional SMN proteins. These proteins are essential for normal motor neuron function. The outcome of missing SMN proteins is a deterioration of motor neurons in the spinal cord and brain resulting in a dysfunction of voluntary muscle movements and inevitably in progressive muscular weakness. In most cases, motor skills will not be obtained or motor skills already acquired are often lost.