A 7-year delayed diagnosis in a case of spinal muscular atrophy

Most cases of spinal muscular atrophy (SMA) can be diagnosed by copy number analysis of survival motor neuron (SMN) 1. However, a small number of cases of SMA can only be diagnosed by sequencing analysis. We present a case of SMA diagnosed 7 years after the onset of symptoms.

She was a 12-year-old girl of Sri Lankan origin. At age 5, she began to fall easily. She had normal intellectual development, and electromyography suggested a neurogenic disorder. Copy number analysis of SMN1 exons 7 and 8 via polymerase chain reaction revealed at least one copy of SMN1. Exome sequence analysis for neuromuscular disorders panel could not detect the pathogenic mutation. She moved to Japan at the age of 12 years. Sequencing analysis later identified a novel mutation in SMN1 at the same locus as previously reported (c.284G>A: p.Gly95Glu). Multiple ligation-dependent probe amplification indicated she had two copies of SMN2. She was diagnosed with SMA type 3b and treated with nusinersen.

In patients with SMA, 2-5 % have a point mutation or a small insertion/deletion in SMN1. Since copy number analysis cannot detect such mutations, sequencing analysis is required. Two copies of SMN2 often result in SMA type 1 or 2, but her mild symptoms of SMA type 3b may be due to a combination of a point mutation and a deletion in SMN1.

Even if genetic testing has been performed at previous institutions, sequencing analysis should be considered if the patient's symptoms are consistent with SMA.