| Spinal muscular atrophies | |
|---|---|
 | |
| Location of neurons affected in spinal muscular atrophies | |
| Specialty | Neurology |
| Symptoms | Loss ofmotor neurons resulting inmuscle wasting |
Spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration oflower motor neurons (neuronal cells situated in theanterior horn of the spinal cord) and subsequentatrophy (wasting) of variousmuscle groups in the body.[1] While some SMAs lead to early infant death, other diseases of this group permit normal adult life with only mild weakness.
Based on the type of muscles affected, spinal muscular atrophies can be divided into:[citation needed]
When taking into accountprevalence, spinal muscular atrophies are traditionally divided into:[citation needed]
A more detailed classification is based on thegene associated with the condition (where identified) and is presented in table below.
| Group | Name Alternative names | OMIM | Gene | Locus | Mode of inheritance | Characteristics |
|---|---|---|---|---|---|---|
| SMA | Spinal muscular atrophy (SMA)
| 253300 253550 253400 271150 | SMN1 | 5q13.2 | 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 primarilybulbar muscles as well assensory nerves mainly in adult men, progressive |
X-linked spinal muscular atrophy type 2 (SMAX2)
| 301830 | UBA1 | Xp11.23 | X-linked recessive | Characterised by bone fractures, affects mainly distal muscles in newborn boys, usually fatal in infancy | |
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, similar toSMA type 1 but withdiaphragmatic paralysis |
Distal spinal muscular atrophy type 2 (DSMA2)
| 605726 | SIGMAR1 | 19p13.3 | Autosomal recessive | Slowly progressive | |
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 5 (DSMA5) | 614881 | DNAJB2 | 2q35 | Autosomal recessive | Young adult onset, slowly progressive | |
Distal spinal muscular atrophy type VA (DSMAVA)
| 600794 | GARS | 7p14.3 | Autosomal dominant | With upper limb predominance; allelic and overlapping withCMT2D, phenotype overlapping withSilver syndrome | |
Distal spinal muscular atrophy type VB (DSMAVB)
| 614751 | REEP1 | 2p11 | Autosomal dominant | With upper limb predominance; allelic and overlapping withHSP-31 | |
Distal spinal muscular atrophy with calf predominance
| 615575 | FBXO38 | 5q32 | Autosomal dominant | Juvenile- or adult-onset, slowly progressive, affects both proximal and distal muscles, initially manifests with calf weakness which progresses to hands | |
Distal spinal muscular atrophy with vocal cord paralysis
| 158580 | SLC5A7 | 2q12.3 | Autosomal dominant | Adult-onset with vocal cord paralysis, very rare | |
Congenital distal spinal muscular atrophy
| 600175 | TRPV4 | 12q24.11 | Autosomal dominant | Affects primarily distal muscles of lower limbs, non-progressive, rare, allelic withSPSMA andCMT2C | |
Scapuloperoneal spinal muscular atrophy (SPSMA)
| 181405 | TRPV4 | 12q24.11 | Autosomal dominant orX-linked dominant | Affects muscles of lower limbs, non-progressive, rare, allelic withcongenital distal spinal muscular atrophy andCMT2C | |
Autosomal dominant distal spinal muscular atrophy
| 158590 | HSPB8 | 12q24.23 | Autosomal dominant | Adult-onset. Allelic withCharcot–Marie–Tooth disease type 2L (CMT2L) | |
Autosomal dominant juvenile distal spinal muscular atrophy
| 182960 | ? | 7q34–q36 | Autosomal dominant | Juvenile-onset | |
| Juvenile segmental spinal muscular atrophy (JSSMA) | 183020 | ? | 18q21.3 | ? | Juvenile-onset, progressive with stabilisation after 2–4 years, affects primarily hands, very rare | |
| Finkel type proximal spinal muscular atrophy (SMAFK) | 182980 | VAPB | 20q13.32 | Autosomal dominant | Late-onset, affects proximal muscles in adults | |
| James type infantile spinal muscular atrophy (SMAJI) | 619042 | GARS1 | 7p14.3 | Autosomal dominant | Infantile-onset hypotonia, slowly progressive, resulting in delayed motor milestones and loss of previous motor skills. Children never walk. Milder disorders caused byGARS1 mutations areCMT2D andHMN5A. | |
| Jokela type spinal muscular atrophy (SMAJ) | 615048 | CHCHD10 | 22q11.2–q13.2 | Autosomal dominant | Late-onset, slowly progressive, affects both proximal and distal muscles in adults | |
| Spinal muscular atrophy with lower extremity predominance 1 (SMALED1) | 158600 | DYNC1H1 | 14q32 | Autosomal dominant | Affects proximal muscles in infants | |
| Spinal muscular atrophy with lower extremity predominance 2A (SMALED2A) | 615290 | BICD2 | 9q22.31 | Autosomal dominant | Early-onset, primarily affecting lower limbs, slowly progressive, non-life-limiting, very rare | |
| Spinal muscular atrophy with lower extremity predominance 2B (SMALED2B) | 618291 | BICD2 | 9q22.31 | Autosomal dominant | Presents with hypotonia, contractures and respiratory involvement at birth, frequently fatal in early childhood, very rare | |
| Spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) | 159950 | ASAH1 | 8p22 | Autosomal recessive | ||
| Spinal muscular atrophy with congenital bone fractures 1 (SMABF1) | 616866 | TRIP4 | 15q22.31 | Autosomal recessive | Prenatal onset, characterised by severe muscle wasting, respiratory and feeding failure, and bone fractures at birth as inarthrogryposis multiplex congenita, usually fatal in infancy | |
| Spinal muscular atrophy with congenital bone fractures 2 (SMABF2) | 616867 | ASCC1 | 10q22.1 | Autosomal recessive | Prenatal onset, characterised by severe muscle wasting, respiratory and feeding failure, and bone fractures at birth as inarthrogryposis multiplex congenita, usually fatal in infancy[2][3][4] | |
| PCH | Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH)
| 607596 | VRK1 | 14q32 | Autosomal dominant | → seePontocerebellar hypoplasia |
| MMA | Juvenile asymmetric segmental spinal muscular atrophy (JASSMA)
| 602440 | ? | ? | ? | → seeMonomelic amyotrophy |
| PMA | Progressive spinal muscular atrophy
| ? | ? | ? | ? | → seeProgressive muscular atrophy |
In all forms of SMA (with an exception ofX-linked spinal muscular atrophy type 1), onlymotor neurons, located at theanterior horn of spinal cord, are affected;sensory neurons, which are located at theposterior horn of spinal cord, are not affected. By contrast, hereditary disorders that cause both weakness due to motor denervation along withsensory impairment due to sensory denervation are known ashereditary motor and sensory neuropathies (HMSN).[citation needed]