Congenital Myasthenic Syndromes (CMS)

Signs and Symptoms

As its name implies, congenital myasthenic syndromes (CMS) usually have a congenital (at or near birth) onset, but the disease can manifest in children and even in adults. The different types vary in the kind and degree of symptoms, but generally speaking, the earlier the symptoms appear, the more pronounced the disease is likely to be.

Presynaptic CMS has its onset in infancy and can cause ocular weakness — weakness in muscles controlling the eyes — which can cause droopy eyelids (ptosis). It also causes bulbar weakness (named for the nerves that originate from the bulblike part of the brainstem) making it difficult to talk, chew, swallow and hold up the head. Some patients have episodes of apnea, a temporary cessation of breathing.

Certain types of postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) are caused by ACh receptors that are missing or do not stay open long enough. These types have symptoms ranging from mild to extreme. In infants, they may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis (droopy eyelids) and fatigue, but usually don’t interfere with daily living.

Another type of postsynaptic CMS (slow-channel CMS) is caused by ACh receptors that stay open too long. This type causes extreme weakness in infant-onset cases, often leading to loss of mobility and respiratory problems in adolescence. Childhood and adult-onset cases may not be disabling.

Synaptic CMS is caused by deficiency of acetylcholinesterase, an enzyme that breaks down ACh. It can cause extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones and often leads to reduced mobility and scoliosis (curvature of the spine).

Additional reading

• Abicht A, Müller JS, Lochmüller H. Congenital Myasthenic Syndromes Overview. 2003 May 9 [Updated 2021 Dec 23]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1168/
• 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. PMID: 39051439; PMCID: PMC11377046.

Last reviewed: August 2025