Classification
Based on the type of muscles affected, spinal muscular atrophies can be divided into:
- Proximal spinal muscular atrophies, i.e., conditions that affect primarily proximal muscles;
- Distal spinal muscular atrophies (which significantly overlap with distal hereditary motor neuropathies) where they affect primarily distal muscles.
When taking into account prevalence, spinal muscular atrophies are traditionally divided into::
- Autosomal recessive proximal spinal muscular atrophy, responsible for 90-95% of cases and usually called simply spinal muscular atrophy (SMA) – a disorder associated with a genetic mutation on the SMN1 gene on chromosome 5q (locus 5q13), affecting people of any age but in its most severe form being the most common genetic cause of infant death;
- Localised spinal muscular atrophies – much more rare conditions, in some instances described in but a few patients in the world, which are associated with mutations of genes other than SMN1 and for this reason sometimes termed simply non-5q spinal muscular atrophies.
A more detailed classification is based on the gene associated with the condition (where identified) and is presented in table below.
| Group | Name |
OMIM | Gene | Locus | Inheritance | Characteristics |
|---|---|---|---|---|---|---|
| SMA | Spinal muscular atrophy (SMA)
|
(multiple) | SMN1 | 5q13 | Autosomal recessive | Affects primarily proximal muscles in people of all ages, progressive, relatively common |
| XLSMA | X-linked spinal muscular atrophy type 1 (SMAX1)
|
313200 | NR3C4 | Xq12 | X-linked recessive | Affects primarily bulbar muscles as well as sensory nerves mainly in adult men, progressive |
| X-linked spinal muscular atrophy type 2 (SMAX2)
|
301830 | UBE1 | Xp11.23 | X-linked recessive | Affects distal muscles mainly in newborn boys | |
| X-linked spinal muscular atrophy type 3 (SMAX3)
|
300489 | ATP7A | Xq21.1 | X-linked recessive | Affects distal muscles of all extremities mainly in boys, slowly progressive | |
| DSMA | Distal spinal muscular atrophy type 1 (DSMA1)
|
604320 | IGHMBP2 | 11q13.3 | Autosomal recessive | Affects mainly infant boys, progressive with diaphragmatic paralysis |
| Distal spinal muscular atrophy type 2 (DSMA2)
|
605726 | ? | 9p21.1–p12 | Autosomal recessive | Slowly progressive, described only in one family | |
| Distal spinal muscular atrophy type 3 (DSMA3)
|
607088 | ? | 11q13.3 | Autosomal recessive | Slowly progressive | |
| Distal spinal muscular atrophy type 4 (DSMA4) | 611067 | PLEKHG5 | 1p36.31 | Autosomal recessive | Slowly progressive, described only in one family | |
| Distal spinal muscular atrophy type 5A (DSMA5A)
|
600794 | GARS | 7p14.3 | Autosomal dominant | With upper limb predominance; allelic and overlapping with CMT2D, phenotype overlapping with Silver syndrome | |
| Distal spinal muscular atrophy type 5B (DSMA5B)
|
614751 | REEP1 | 2p11 | Autosomal dominant | With upper limb predominance; allelic and overlapping with HSP-31 | |
| Distal spinal muscular atrophy with vocal cord paralysis
|
158580 | ? | 2q14.2 | Autosomal dominant | Adult-onset with vocal cord paralysis, very rare | |
| ADSMA | Autosomal dominant distal spinal muscular atrophy
|
158590 | HSPB8 | 12q24.23 | Autosomal dominant | |
| Autosomal dominant proximal spinal muscular atrophy | 182980 | VAPB | 20q13.32 | Autosomal dominant | Affects proximal muscles in adults | |
| Congenital distal spinal muscular atrophy | 600175 | TRPV4 | 12q24.11 | Autosomal dominant | Affects primarily distal muscles of lower limbs, non-progressive, rare, allellic with SPSMA and CMT2C | |
| Scapuloperoneal spinal muscular atrophy (SPSMA)
|
181405 | TRPV4 | 12q24.11 | Autosomal dominant or X-linked dominant |
Affects muscles of lower limbs, non-progressive, rare, allelic with congenital distal spinal muscular atrophy and CMT2C | |
| Segmental spinal muscular atrophy | 183020 | (multiple) | 18q21.3 | ? | Affects primarily hands, non-progressive, rare | |
| Spinal muscular atrophy with lower extremity predominance (SMA-LED) | 158600 | DYNC1H1 | 14q32 | Autosomal dominant | Affects proximal muscles in infants, rare | |
| Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) | 159950 | ASAH1 | 8p22 | Autosomal recessive | ||
| Spinal muscular atrophy with congenital bone fractures (SMA-CBF) | 271225 | ? | ? | Autosomal recessive (?) | Characterised by congenital bone fractures on top of typical muscle weakness; described only in a handful of infants | |
| Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH)
|
607596 | VRK1 | 14q32 | Autosomal dominant | → see Pontocerebellar hypoplasia | |
| Juvenile asymmetric segmental spinal muscular atrophy (JASSMA)
|
602440 | ? | ? | ? | → see Monomelic amyotrophy |
In all forms of SMA (with an exception of X-linked spinal muscular atrophy type 1), only motor neurons, located at the anterior horn of spinal cord, are affected; sensory neurons, which are located at the posterior horn of spinal cord, are not affected. By contrast, hereditary disorders that cause both weakness due to motor denervation along with sensory impairment due to sensory denervation are known as hereditary motor and sensory neuropathies (HMSN).
Read more about this topic: Spinal Muscular Atrophies