Congenital myasthenic syndromes

Congenital myasthenic syndromes are a group of conditions that are characterized by weak muscles that tire easily (myasthenia). In people with these conditions, myasthenia typically begins shortly after birth or during early childhood. The most commonly affected muscles are the muscles in the head and neck (bulbar muscles) that control chewing and swallowing, speech, and facial expressions; the muscles that move the eyes and eyelids; and the muscles in the arms and legs. However, any of the muscles used for movement (skeletal muscles) can be affected.

In individuals with congenital myasthenic syndromes, episodes of severe weakness or breathing problems may be triggered by fevers, infection, or tiring physical activity. The severity of the myasthenia varies greatly, from minor muscle weakness to severe weakness that may require wheelchair assistance.

Babies with congenital myasthenic syndromes may have feeding difficulties. Some affected babies may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis). In severe instances, a lack of movement before birth can lead to joint deformities (contractures) that cause joint stiffness (arthrogryposis) and impair movement.

Children with congenital myasthenic syndromes may have speech problems (dysarthria) or swallowing difficulties (dysphagia). The development of motor skills, such as crawling or walking, may be delayed in these children.

The prevalence of congenital myasthenic syndromes is estimated to be 2 in 1 million individuals worldwide. In people under 18 years of age, the prevalence is estimated to be 10 in 1 million individuals.

Variants (also called mutations) in more than 35 genes can cause congenital myasthenic syndromes. Variants in the CHRNE gene are responsible for about half of all cases. Variants in the COLQ and DOK7 genes are responsible for 20 to 30 percent of all cases. Variants in other genes are each responsible for a small percentage of cases.

All of the genes that are associated with congenital myasthenic syndromes provide instructions for producing proteins that are involved in the normal function of the neuromuscular junction. The neuromuscular junction is the area between nerve cells and muscle cells where signals are passed on to trigger muscle movement.

The gene variants that cause congenital myasthenic syndromes lead to changes in these proteins and disrupt the signaling between nerve cells and muscle cells. Disrupted signaling between these cells impairs the ability to move skeletal muscles. This leads to myasthenia, which affects facial muscle movements, delays the development of motor skills, and causes the other signs and symptoms of congenital myasthenic syndromes. The breathing problems seen in people with congenital myasthenic syndromes are caused by impaired movement of the muscles of the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm).

Congenital myasthenic syndromes can be sorted into subtypes in several different ways. For example, they can be sorted by the genetic cause, the specific function of the associated gene, or the location in the cell where the associated gene functions.

Treatment of congenital myasthenic syndromes is often determined by the specific genetic cause.

Some people with congenital myasthenic syndromes do not have an identified variant in any of the genes known to be associated with these conditions. The cause of the conditions in these individuals is unknown.

Genetic Testing Information

• Genetic Testing Registry: Congenital myasthenic syndrome

Genetic and Rare Diseases Information Center

• Congenital myasthenic syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• MYASTHENIC SYNDROME, CONGENITAL, 1A, SLOW-CHANNEL; CMS1A
• MYASTHENIC SYNDROME, CONGENITAL, 6, PRESYNAPTIC; CMS6
• MYASTHENIC SYNDROME, CONGENITAL, 10; CMS10
• MYASTHENIC SYNDROME, CONGENITAL, 5; CMS5
• MYASTHENIC SYNDROME, CONGENITAL, 1B, FAST-CHANNEL; CMS1B
• MYASTHENIC SYNDROME, CONGENITAL, 4C, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS4C
• MYASTHENIC SYNDROME, CONGENITAL, 4A, SLOW-CHANNEL; CMS4A
• MYASTHENIC SYNDROME, CONGENITAL, 12; CMS12
• MYASTHENIC SYNDROME, CONGENITAL, 7A, PRESYNAPTIC, AND DISTAL MOTOR NEUROPATHY, AUTOSOMAL DOMINANT; CMS7A
• MYASTHENIC SYNDROME, CONGENITAL, 17; CMS17
• MYASTHENIC SYNDROME, CONGENITAL, 2A, SLOW-CHANNEL; CMS2A
• MYASTHENIC SYNDROME, CONGENITAL, 2C, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS2C
• MYASTHENIC SYNDROME, CONGENITAL, 3A, SLOW-CHANNEL; CMS3A
• MYASTHENIC SYNDROME, CONGENITAL, 3B, FAST-CHANNEL; CMS3B
• MYASTHENIC SYNDROME, CONGENITAL, 3C, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS3C
• MYASTHENIC SYNDROME, CONGENITAL, 4B, FAST-CHANNEL; CMS4B
• MYASTHENIC SYNDROME, CONGENITAL, 9, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS9
• MYASTHENIC SYNDROME, CONGENITAL, 11, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS11
• MYASTHENIC SYNDROME, CONGENITAL, 25, PRESYNAPTIC; CMS25
• MYASTHENIC SYNDROME, CONGENITAL, 8; CMS8
• MYASTHENIC SYNDROME, CONGENITAL, 16; CMS16
• MYASTHENIC SYNDROME, CONGENITAL, 20, PRESYNAPTIC; CMS20
• MYASTHENIC SYNDROME, CONGENITAL, 23, PRESYNAPTIC; CMS23
• MYASTHENIC SYNDROME, CONGENITAL, 24, PRESYNAPTIC; CMS24
• MYASTHENIC SYNDROME, CONGENITAL, 19; CMS19
• MYASTHENIC SYNDROME, CONGENITAL, 13; CMS13
• MYASTHENIC SYNDROME, CONGENITAL, 21, PRESYNAPTIC; CMS21
• MYASTHENIC SYNDROME, CONGENITAL, 22; CMS22
• MYASTHENIC SYNDROME, CONGENITAL, 15; CMS15
• MYASTHENIC SYNDROME, CONGENITAL, 14; CMS14
• MYASTHENIC SYNDROME, CONGENITAL, 7B, PRESYNAPTIC, AUTOSOMAL RECESSIVE; CMS7B

Scientific Articles on PubMed

• PubMed

• Abicht A, Muller JS, Lochmuller H. Congenital Myasthenic Syndromes Overview. 2003 May 9 [updated 2021 Dec 23]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1168/ Citation on PubMed
• Estephan EP, Zambon AA, Thompson R, Polavarapu K, Jomaa D, Topf A, Helito PVP, Heise CO, Moreno CAM, Silva AMS, Kouyoumdjian JA, Morita MDP, Reed UC, Lochmuller H, Zanoteli E. Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis. Eur J Neurol. 2022 Mar;29(3):833-842. doi: 10.1111/ene.15173. Epub 2021 Nov 17. Citation on PubMed
• Finsterer J. Congenital myasthenic syndromes. Orphanet J Rare Dis. 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. Citation on PubMed
• Ohno K, Ito M, Ohkawara B. Review of 40 genes causing congenital myasthenic syndromes. J Hum Genet. 2025 Jun 18. doi: 10.1038/s10038-025-01355-9. Online ahead of print. Citation on PubMed
• Ohno K, Ohkawara B, Shen XM, Selcen D, Engel AG. Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review. Int J Mol Sci. 2023 Feb 13;24(4):3730. doi: 10.3390/ijms24043730. Citation on PubMed
• Prior DE, Ghosh PS. Congenital Myasthenic Syndrome From a Single Center: Phenotypic and Genotypic features. J Child Neurol. 2021 Jul;36(8):610-617. doi: 10.1177/0883073820987755. Epub 2021 Jan 20. Citation on PubMed
• Ramdas S, Beeson D, Dong YY. Congenital myasthenic syndromes: increasingly complex. Curr Opin Neurol. 2024 Oct 1;37(5):493-501. doi: 10.1097/WCO.0000000000001300. Epub 2024 Jul 25. Citation on PubMed
• Spendiff S, Lochmuller H, Maselli RA. Congenital myasthenic syndromes. Int Rev Neurobiol. 2025;182:253-274. doi: 10.1016/bs.irn.2025.04.025. Epub 2025 May 16. Citation on PubMed