Table 1.
Electrophysiological features and therapies of congenital myasthenic syndromes.
| Section | Phenotype | Gene | OMIM | # a | Inheritance | Low-Frequency RNS | High-Frequency RNS | Treatment | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ChEIs | Ephedrine | Salbutamol (albuterol) | Amifampridine | Quinidine | Fluoxetine | Acetazolamide | |||||||||
| 4.1 | Endplate AChR deficiency | CHRNA1 | - b | AR | decrement | effective | effective | effective | effective | ||||||
| 4.1 | Endplate AChR deficiency | CHRNB1 | CMS2C | - b | AR | decrement | effective | effective | effective | effective | |||||
| 4.1 | Endplate AChR deficiency | CHRND | CMS3C | - b | AR | decrement | effective | effective | effective | effective | |||||
| 4.1 | Endplate AChR deficiency | CHRNE | CMS4C | - b | AR | decrement | effective | effective | effective | effective | |||||
| 4.1 | Endplate AChR deficiency | RAPSN | CMS11 | [38] | AR | decrement | effective | effective | effective | effective | |||||
| 4.2 | Escobar syndrome | CHRNG | 101 | AR | decrement | ||||||||||
| 4.2 | FADS | CHRNA1 | (4) | AR | decrement | ||||||||||
| 4.2 | FADS | CHRND | (6) | AR | decrement | ||||||||||
| 4.2 | FADS | MUSK | (6) | AR | decrement | ||||||||||
| 4.2 | FADS | RAPSN | (8) | AR | decrement | ||||||||||
| 4.2 | FADS | DOK7 | (2) | AR | decrement | ||||||||||
| 4.2 | FADS | SLC18A3 | (1) | AR | decrement | ||||||||||
| 4.3 | SCCMS | CHRNA1 | CMS1A | (14) | AD | decrement, repetitive CMAP | mostly ineffective | effective in some reports | effective in some reports | effective | effective | ||||
| 4.3 | SCCMS | CHRNB1 | CMS2A | (5) | AD | decrement, repetitive CMAP | mostly ineffective | effective in some reports | effective in some reports | effective | effective | ||||
| 4.3 | SCCMS | CHRND | CMS3A | (4) | AD | decrement, repetitive CMAP | mostly ineffective | effective in some reports | effective in some reports | effective | effective | ||||
| 4.3 | SCCMS | CHRNE | CMS4A | (11) | AD/AR | decrement, repetitive CMAP | mostly ineffective | effective in some reports | effective in some reports | effective | effective | ||||
| 4.3 | FCCMS | CHRNA1 | CMS1B | (3) c | AR | decrement | effective | presumably effective, but no report | effective in a report | effective | |||||
| 4.3 | FCCMS | CHRNB1 | CMS2B | (1) c | AR | decrement | effective | presumably effective, but no report | effective in a report | effective | |||||
| 4.3 | FCCMS | CHRND | CMS3B | (1) c | AR | decrement | effective | presumably effective, but no report | effective in a report | effective | |||||
| 4.3 | FCCMS | CHRNE | CMS4B | (6) c | AR | decrement | effective | presumably effective, but no report | effective in a report | effective | |||||
| 4.4 | Endplate AChE deficiency | COLQ | CMS5 | [30] | AR | decrement, repetitive CMAP | contraindication, but effective in some reported patients | effective in some reports | effective in some reports | effective in a report | |||||
| 4.4 | Synaptic CMS | LAMB2 | 1 | AR | decrement | contraindication | effective | ||||||||
| 4.4 | Synaptic CMS | COL13A1 | CMS19 | 41 | AR | decrement | ineffective | effective | effective | ||||||
| 4.5 | Sodium channel CMS | SCN4A | CMS16 | 6 | AR | no decrement | decrement | Effective, ineffective, or marked adverse effects | Slightly effective | effective or ineffective | |||||
| 4.6 | CMS caused by defective AChR clustering | AGRN | CMS8 | [13] | AR | decrement | Ineffective or mildly effective | effective | effective | ineffective or slightly effective | |||||
| 4.6 | CMS caused by defective AChR clustering | MUSK | CMS9 | [15] | AR | decrement | Ineffective or worsened | effective | effective | ||||||
| 4.6 | CMS caused by defective AChR clustering | LRP4 | CMS17 | 1 | AR | decrement | worsened | ||||||||
| 4.6 | CMS caused by defective AChR clustering | DOK7 | CMS10 | [34] | AR | decrement | Combination of ineffective and worsening | effective | effective | effective in some reports | effective in some reports | ||||
| 4.7 | CMS caused by defective structural molecules | PLEC | 22 | AR | decrement | effective or ineffective | effective in some reports | effective or ineffective | |||||||
| 4.8 | CMS caused by defective recycling of ACh | CHAT | CMS6 | [19] | AR | no decrement | decrement in some patients | effective | effective | ||||||
| 4.8 | CMS caused by defective recycling of ACh | SLC18A3 | CMS21 | 7 | AR | decrement at rest or only after isometric muscle contraction | decrement in some patients | effective | effective | effective | |||||
| 4.8 | CMS caused by defective recycling of ACh | SLC5A7 | CMS20 | 12 | AR | decrement at rest or only after isometric muscle contraction | decrement in some patients | effective | effective | ineffective | |||||
| 4.8 | CMS caused by defective recycling of ACh | PREPL | CMS22 | 18 | AR | decrement | decrement in some patients | effective | |||||||
| 4.9 | LEMS-like CMS | SYT2 | CMS7ACMS7B | 2 | AD/AR | decrement | increment | effective | effective | effective | |||||
| 4.9 | LEMS-like CMS | SNAP25 | CMS18 | 2 | AD | decrement | ineffective | effective | |||||||
| 4.9 | LEMS-like CMS | UNC13A | 1 | AR | decrement | increment | minimally effective | minimally effective | |||||||
| 4.9 | LEMS-like CMS | VAMP1 | CMS25 | 9 | AR | decrement | increment | effective | |||||||
| 4.9 | LEMS-like CMS | RPH3A | 1 | AR | no decrement | increment | effective | ||||||||
| 4.9 | LEMS-like CMS | LAMA5 | 1 | AR | decrement | increment | effective | effective | |||||||
| 4.10 | Glycosylation-deficient CMS | GFPT1 | CMS12 | [17] | AR | decrement | effective | effective | |||||||
| 4.10 | Glycosylation-deficient CMS | DPAGT1 | CMS13 | [5] | AR | decrement | effective | effective | effective | ||||||
| 4.10 | Glycosylation-deficient CMS | ALG2 | CMS14 | 9 | AR | decrement | effective or ineffective | effective | effective | ||||||
| 4.10 | Glycosylation-deficient CMS | ALG14 | CMS15 | 12 | AR | decrement | effective | ||||||||
| 4.10 | Glycosylation-deficient CMS | GMPPB | [9] | AR | decrement | effective | effective | ||||||||
| 4.11 | CMS caused by defective nerve terminal formation | MYO9A | CMS24 | 3 | AR | decrement | effective | effective | |||||||
| 4.11 | CMS caused by defective nerve terminal formation | SLC25A1 | CMS23 | 19 | AR | decrement | ineffective in most patients | ineffective in most patients | |||||||
| 4.12 | CMS caused by defective nuclear membrane protein | TOR1AIP1 | 5 | AR | decrement | effective | no additional effect | ||||||||
| 4.13 | CMS caused by defective chromatin remodeling protein | CHD8 | 2 | AR | decrement | ineffective | ineffective | markedly effective | |||||||
| 4.14 | CMS in PURA syndrome | PURA | 3 | AD | decrement, repetitive CMAP | effective in a patient, but not in another patient | effective in a patient | ||||||||
a The number of original reports is shown in square brackets, and the number of pathogenic variants in round brackets. Otherwise, the number of patients is shown. b Differentiation of endplate AChR deficiency and FCCMS requires detailed electrophysiological studies using either intracellular recordings or patch-clamp recordings of biopsied patient’s neuromuscular junction, or patch-clamp recordings of mutant AChRs expressed in culture cells, but most variants are not characterized as such. Thus, the numbers of patients, original articles, pathogenic variants of endplate AChR deficiency were not counted. c For FCCMS, the number of pathogenic variants with electrophysiological analyses was counted.