Table 1 Different subtypes of familial ALS and their genotype–phenotype correlations
From: Genotype-phenotype correlations of amyotrophic lateral sclerosis
ALS type | Gene | Inheritance | ALS features | FTD | Other features/disorders |
|---|---|---|---|---|---|
(chromosome) | |||||
ALS 1 | SOD1 | AD; AR; | AAO: adult > juvenile; Onset: LL > UL > bulbar; | Rare | PMA, PBP, BFA, cerebellar ataxia, autonomic dysfunction |
(21q22.1) | De novo | Progression: rapid > slow; UMN + LMN > LMN dominant | |||
ALS 2 | ALSIN | AR | AAO: juvenile; Onset: LL, UL; | None | PLS, IAHSP |
(2q33.2) | Progression: slow; UMN dominant > UMN + LMN | ||||
ALS 3 | UN | AD | N/A | N/A | N/A |
(18q21) | |||||
ALS 4 | SETX | AD | AAO: juvenile > adult; Onset: LL > UL; | None | AOA2, cerebellar ataxia, motor neuropathy |
(9q34) | Progression: slow; UMN + LMN > LMN dominant | ||||
ALS 5 | SPG11 | AR | AAO: juvenile > adult; Onset: bulbar, limb; | Rare | HSP, autonomic dysfunction, mental retardation |
(15q21.1) | Progression: slow; UMN dominant > UMN + LMN | ||||
ALS 6 | FUS | AD; AR; | AAO: adult > juvenile; Onset: UL, bulbar > LL; | Rare | PMA, Parkinsonism, essential tremor, mental retardation |
(16q11.2) | De novo | Progression: rapid > slow; UMN + LMN > LMN dominant | |||
ALS 7 | UN | AD | N/A | N/A | N/A |
(20p13) | |||||
ALS 8 | VAPB | AD | AAO: adult > juvenile; Onset: limb; | None | SMA, motor neuropathy, autonomic dysfunction |
(20q13.3) | Progression: slow; LMN dominant | ||||
ALS 9 | ANG | AD | AAO: adult > juvenile; Onset: limb, bulbar; | Yes | PBP, PD |
(14q11.2) | |||||
Progression: N/A; UMN + LMN | |||||
ALS 10 | TARDBP | AD; AR | AAO: adult; Onset: limb, bulbar; | Yes | PSP, FTD with Parkinsonism, PD, chorea |
(1p36.22) | Progression: variable; UMN + LMN | ||||
ALS 11 | FIG4 | AD | AAO: adult; Onset: bulbar > limb; | None | CMT4J, HSP, PLS, Yunis–Varon syndrome, epilepsy with polymicrogyria |
(6q21) | Progression: variable; UMN + LMN > UMN dominant | ||||
ALS 12 | OPTN | AD; AR | AAO: adult; Onset: bulbar, limb; | Yes | POAG, Parkinsonism, aphasia |
(10p13) | Progression: slow; UMN + LMN | ||||
ALS 13 | ATXN2 | AD | AAO: adult > juvenile; Onset: UL, LL; | None | SCA2, Parkinsonism |
(12q24) | Progression: variable; UMN + LMN | ||||
ALS 14 | VCP | AD | AAO: adult > juvenile; Onset: limb > bulbar; | Yes | IBMPFD |
(9p13) | Progression: variable; UMN + LMN | ||||
ALS 15 | UBQLN2 | XD | AAO: adult > juvenile; Onset: limb, bulbar; | Yes | PLS |
(Xp11.21) | Progression: variable; UMN + LMN > UMN dominant | ||||
ALS 16 | SIGMAR1 | AD | AAO: juvenile; Onset: LL > UL; | Rare | motor neuropathy |
(9p13.3) | Progression: N/A; UMN + LMN | ||||
ALS 17 | CHMP2B | AD | AAO: adult; Onset: bulbar, limb; | Yes | PMA; Parkinsonism |
(3p12.1) | Progression: N/A; UMN + LMN > LMN dominant | ||||
ALS 18 | PFN1 | AD | AAO: adult; Onset: limb; | None | N/A |
(17p13.2) | Progression: N/A; UMN + LMN | ||||
ALS 19 | ERBB4 | AD | AAO: adult; Onset: UL, bulbar; | None | N/A |
(2q33.3-q34) | Progression: slow; UMN + LMN | ||||
ALS 20 | hnRNPA1 | AD | AAO: adult; Onset: N/A; | Yes | multisystem proteinopathy |
(12q13.1) | Progression: N/A; UMN + LMN > LMN dominant | ||||
ALS 21 | MATR3 | AD | AAO: adult; Onset: bulbar, limb; | Yes | distal myopathy |
(5q31.3) | Progression: slow; UMN + LMN > LMN dominant | ||||
ALS-FTD | C9ORF72 | AD | AAO: adult; Onset: bulbar, limb; | Yes | Parkinsonism, cerebellar ataxia |
(9p21.2) | Progression: rapid > slow; UMN + LMN |