Spinal Muscular Atrophies (SMA) include a group of neuromuscular disorders characterized by degeneration of alpha motor neurons in the spinal cord with progressive muscle atrophy, weakness and paralysis.

The phenotypes are grouped on the basis of the classical age of the onset and maximum motor function achieved: very weak infants unable to sit unsupported (type 1), non-ambulant patients able to sit independently (type 2), up to ambulant patients with childhood (type 3) and adult-onset SMA (type 4).

More than 90% of cases of SMA result from deletions or mutations of Survival Motor Neuron 1 (SMN1) gene, usually homozygous absence of exons 7 and 8 of the SMN1 gene, or only of exon 7. The majority of patients inherit the SMN1 deletion from their parents. The SMN locus is part of a genomic inverted duplication region on human chromosome 5, which contains a paralogue gene, SMN2. SMN2, a nearly identical copy of SMN1, does not compensate for the loss of SMN1 due to the predominant skipping of exon 7.

The diagnosis of SMA is based on molecular genetic testing. Genetic testing of SMN1/SMN2 is highly reliable and it is the first-line investigation when the condition is suspected in a typical case, then there is no need for a muscle biopsy.

A standard of SMA genetic testing is a quantitative analysis of both SMN1 and SMN2 using multiplex ligation-dependent probe amplification (MLPA), quantitative polymerase chain reaction (qPCR) or next-generation sequencing (NGS).

The incidence is approximately 10 in 100,000 live births.

A correction of SMN2 exon 7 splicing has proven to confer therapeutic benefits in SMA patients. The approved drug for SMA is an antisense oligonucleotide that corrects SMN2 exon 7 splicing by blocking intronic splicing silencer N1 (ISS-N1) located immediately downstream of exon 7. 

Reference:

E.Mercuri, et al 2017 ; RN Singh, NN Singh 2018

Last modified
6 April 2021
Abbreviation
SMA
OMIM

# 253300 SPINAL MUSCULAR ATROPHY, TYPE I; SMA1

# 253550 SPINAL MUSCULAR ATROPHY, TYPE II; SMA2

# 253400 SPINAL MUSCULAR ATROPHY, TYPE III; SMA3

# 271150 SPINAL MUSCULAR ATROPHY, TYPE IV; SMA4

ORPHA

ORPHA:83330 Proximal spinal muscular atrophy type 1 or Werndig-Hoffman disease

ORPHA:83418 Proximal spinal muscular atrophy type 2 Intermediate spinal muscular atrophy

ORPHA:83419 Proximal spinal muscular atrophy type 3 or Kugelberg-Welander disease

ORPHA:83420 Proximal spinal muscular atrophy type 4 Spinal muscular atrophy, adult form