| Source | Year/month | Design | N | Key genotype findings | Key phenotype/outcome/treatment findings | URL/DOI |
|---|---|---:|---:|---|---|---|
| Theuriet et al., *Brain* | 2024-05 | French nationwide retrospective adult cohort | 235 | Pathogenic variants in 19 genes; most common genotypes: **CHRNE-low expressor 23.8%**, **DOK7 18.7%**, **RAPSN 14%**. Clinical clusters: ocular (CHRNE-LE, CHRND, FCCMS), distal (SCCMS), limb-girdle (RAPSN, COLQ, DOK7, GMPPB, GFPT1), variable phenotype (MUSK, AGRN). (pqac-00000000, pqac-00000009) | Mean follow-up **34 years**; diagnosis made in adulthood in **139/235** despite childhood onset in most. ICU admission >20% in RAPSN **54.8%**, MUSK **50%**, DOK7 **38.6%**, AGRN **25.0%**. At last visit, ventilation required in **55% of SCCMS** and **36.3% of DOK7** patients; wheelchair use in **36.3% DOK7**, **25% GMPPB**, **20% GFPT1**; **6 deaths**. Authors concluded therapy had a “striking” positive impact and prognosis was favorable for most patients. (pqac-00000000, pqac-00000009) | https://doi.org/10.1093/brain/awae124 |
| Polavarapu et al., *Brain* (Indian cohort) | 2024-09 (advance online 2023-09-18) | Large single-country genetically characterized cohort | 156 patients / 141 families | Variants in **17 CMS-associated genes** in **132/141 families (93.6%)**; distribution: postsynaptic **62.4%**, glycosylation **21.3%**, synaptic basal lamina **4.3%**, presynaptic **2.8%**, other NMJ genes (DES, TEFM) **2.8%**. Most common genes: **CHRNE 39.4%**, **DOK7 14.4%**, **DPAGT1 9.8%**, **GFPT1 7.6%**, **MUSK 6.1%**, **GMPPB 5.3%**, **COLQ 4.5%**; 22 recurrent variants, including suspected founder alleles. (pqac-00000008) | Age at onset ranged from congenital to fourth decade; mean onset **6.6 years**; mean diagnosis age **19 years**; mean diagnostic delay **12.5 years**. Study emphasized major geographic variability in CMS genotype frequencies and the increasing contribution of glycosylation genes in India. (pqac-00000008) | https://doi.org/10.1093/brain/awad315 |
| Smeets et al., *Pediatric Neurology* (Belgium) | 2024-09 | National retrospective pediatric/adult cohort | 37 | Pathogenic variants in **CHRNE, RAPSN, DOK7, PREPL, CHRNB1, CHRNG, COLQ, MUSK, CHRND, GFPT1, GMPPB**; **CHRNE** most common. Most CMS variants recessive; dominant inheritance noted for slow-channel syndromes and presynaptic **SNAP25/SYT2**-related disease. (pqac-00000001, pqac-00000012) | Estimated Belgian prevalence **3.19 per 1,000,000**. Most had onset at birth/infancy/childhood, but **7 adult-onset** cases were identified (CHRNE, DOK7, MUSK, CHRND, GMPPB). RNS performed in 23 patients; **18/23** showed pathologic decrement. Authors noted treatment responses were usually predictable from genotype and stressed molecular diagnosis to tailor therapy. (pqac-00000001, pqac-00000012) | https://doi.org/10.1016/j.pediatrneurol.2024.06.002 |
| Ohno et al., *International Journal of Molecular Sciences* | 2023-02 | Comprehensive review | 35 genes / 442 cited articles | Defined CMS as caused by germline pathogenic variants in **35 genes**: AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MUSK, MYO9A, PLEC, PREPL, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TOR1AIP1, UNC13A, VAMP1; classified into **14 groups**. (pqac-00000002, pqac-00000003, pqac-00000016) | Stated that RNS-elicited CMAP measurement is required for diagnosis and that clinical/electrophysiologic features alone cannot identify the defective molecule; genetic testing is always required. Most CMS present before age 2, though onset can occur later. Cholinesterase inhibitors help many groups but are **contraindicated in some**; **ephedrine, salbutamol/albuterol, amifampridine** are effective in many but not all subtypes. Review also highlights episodic apnea in **CHAT-, COLQ-, SCN4A-CMS** and elevated CK in **GMPPB-, GFPT1-, SCCMS**. (pqac-00000002, pqac-00000003, pqac-00000016, pqac-00000018) | https://doi.org/10.3390/ijms24043730 |
| O’Connor et al., *International Journal of Molecular Sciences* | 2023-05 | Review on mitochondrial involvement in CMS/NMJ disease | Review | Highlighted **SLC25A1** and **TEFM** as mitochondria-associated genes reported in suspected CMS; proposed a “**mitochondrial CMS**” subcategory. Noted that mitochondrial defects may impair NMJ transmission at both pre- and postsynapse. (pqac-00000014) | Reported that mitochondrial disease and CMS can overlap clinically and that electrophysiological studies found NMJ abnormalities in **>25%** of a cohort with genetically confirmed primary mitochondrial disease. Emphasized treatment importance because drugs that help one CMS subtype may worsen another; mentioned AChE inhibitors, **3,4-DAP**, and **β2-agonists** (salbutamol, ephedrine) as subtype-dependent options. (pqac-00000014) | https://doi.org/10.3390/ijms24108505 |
| Pugliese et al., *Journal of Neuromuscular Diseases* | 2023-09 | Focused review of presynaptic CMS and animal models | Review | Presynaptic CMS comprise roughly **5–10%** of all CMS; **CHAT** is the commonest presynaptic gene, accounting for **4–5% of all CMS**. Mechanisms include impaired ACh synthesis/recycling, vesicle packaging, release, and presynaptic endplate development/maintenance. (pqac-00000006, pqac-00000015) | Presynaptic CMS usually present prenatally/neonatally with severe phenotypes including arthrogryposis, developmental delay, and apneic crises, but milder proximal-weakness phenotypes also occur. Diagnosis integrates history/exam, **RNS decrement**, **SFEMG jitter/blocking**, and confirmatory sequencing. Review summarizes in vivo models in zebrafish, mouse, *C. elegans*, and *Drosophila* for mechanism and therapy studies. (pqac-00000006, pqac-00000015) | https://doi.org/10.3233/JND-221646 |
| Hesami et al., *Orphanet Journal of Rare Diseases* (COLQ cohort) | 2024-03 | Retrospective genetically confirmed subtype cohort | 26 | **COLQ-CMS** due to 14 variants, including **8 novel variants**; variant classes included **6 missense, 3 frameshift, 3 nonsense, 1 synonymous, 1 CNV**. COLQ encodes the collagen-like tail of acetylcholinesterase and causes synaptic CMS with endplate AChE deficiency. (pqac-00000013) | Mean follow-up **9 years**. Symptom onset from birth to 15 years; delayed motor milestones in **~52%**; sluggish pupils in **~30%**. Low-frequency RNS showed significant decrement in all tested patients; **double CMAP** present in **~75%**. **No benefit from esterase inhibitors**; **ephedrine and salbutamol** were objectively effective in all cases. (pqac-00000013) | https://doi.org/10.1186/s13023-024-03116-x |
| Ziaadini et al., *BMC Neurology* (DOK7 series) | 2024-06 | Case series with literature review | 7 | Genetically confirmed **DOK7-CMS**; most common variant in this series was **c.1124_1127dupTGCC** (3 patients). DOK7 is a common postsynaptic CMS gene associated with limb-girdle presentations and variable age at onset. (pqac-00000017) | Mean onset **12.5 years** (birth to 33 years). Common manifestations: limb-girdle weakness **6/7**, fluctuating symptoms **5/7**, ptosis **4/7**, bifacial weakness **3/7**, reduced extraocular movement **3/7**, bulbar symptoms **2/7**, dyspnea **2/7**. **3-Hz RNS decrement** in **5/6** tested. Authors reported **salbutamol was the most effective** treatment and recommended it as first-line for DOK7 patients. (pqac-00000017) | https://doi.org/10.1186/s12883-024-03713-0 |


*Table: This table compiles the most relevant 2023–2024 CMS cohorts and reviews, emphasizing sample size, geography, genotype distribution, and clinically actionable phenotype/treatment findings. It is useful for quickly comparing broad CMS overviews with subtype-specific cohorts such as COLQ- and DOK7-related disease.*