Congenital myasthenic syndrome (CMS)

Baby Detect > Neurology > Congenital myasthenic syndrome (CMS)

Congenital myasthenic syndrome (CMS) – DOK7, RAPSN, GFPT1, ACHRE, COLQ, CHAT, AGRN, ALG2, ALG14, CHRNA1, CHRNB1, CHRND, GMPPB, COL13A1, DPAGT1, LRP4, MUSK, MYO9A, PREPL, PLEC, SLC25A1, SLC5A7, SNAP25, SYT2, SLC18A3, UNC13A, RPH3A, VAMP1, LAMA5, MACF1 genes

Includes:

– OMIM#254300 https://omim.org/entry/254300

– OMIM#616326 https://omim.org/entry/616326

– OMIM#610542 https://omim.org/entry/610542

– OMIM#605809 https://omim.org/entry/605809

– OMIM#616324 https://omim.org/entry/616324

– OMIM#608931 https://omim.org/entry/608931

– OMIM#603034 https://omim.org/entry/603034

– OMIM#254210 https://omim.org/entry/254210

– OMIM#615120 https://omim.org/entry/615120

– OMIM#616228 https://omim.org/entry/616228

– OMIM#616227 https://omim.org/entry/616227

– OMIM#601462 https://omim.org/entry/601462

– OMIM#616313 https://omim.org/entry/616313

– OMIM#616322 https://omim.org/entry/616322

– OMIM#615352 https://omim.org/entry/615352

– OMIM#616720 https://omim.org/entry/616720

– OMIM#614750 https://omim.org/entry/614750

– OMIM#616304 https://omim.org/entry/616304

– OMIM#616325 https://omim.org/entry/616325

– OMIM#618198 https://omim.org/entry/618198

– OMIM#616224 https://omim.org/entry/616224

– OMIM#613723 https://omim.org/entry/613723

– OMIM#617143 https://omim.org/entry/617143

– OMIM#616330 https://omim.org/entry/616330

– OMIM#616040 https://omim.org/entry/616040

– OMIM#617239 https://omim.org/entry/617239

– OMIM#618323 https://omim.org/entry/618323

– OMIM#618323 https://omim.org/entry/618323

1. The Disease:

Congenital myasthenic syndrome (CMS) is a group of genetic disorders of impaired neuromuscular transmission at the motor endplate characterized by fatigable muscle weakness.

2. The symptoms:

An individual with a congenitalmyasthenic syndrome (CMS) typically presents with a history of fatigable weakness involving ocular, bulbar, and limb muscles with onset at or shortly after birth or in early childhood, usually in the first two years. In its classical presentation, CMS is limited to weakness of the skeletal muscles. Cardiac and smooth muscle are not involved. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. However, in some newly identified CMS subtypes, myasthenia is only one element of a more severe and complex clinical spectrum. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Lack of early signs or symptoms does not exclude the diagnosis.

In the neonatal period. Some myasthenic symptoms are present at birth. Respiratory insufficiency with sudden, episodic apnea and cyanosis are common findings in neonates. Neonates with CMS can have multiple joint contractures (often described as arthrogryposis multiplex congenita) resulting from a lack of foetal movement in utero. Other major findings in the neonatal period may include feeding difficulties, poor suck, and cry, choking spells, eyelid ptosis, and facial, bulbar, and generalized weakness. Stridor in infancy may be an important clue to CMS. In some individuals, long face, narrow jaw, and a high-arched palate have been reported.

During childhood. Individuals with onset later in childhood show abnormal muscle fatigability, with difficulty in running or climbing stairs. Motor milestones may be delayed. Affected individuals present with fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness. Ptosis may involve one or both eyelids. Facial and bulbar weakness with nasal speech and difficulties in coughing and swallowing may be present. Spinal deformity or muscle atrophy may occur.

3. Actions to take in case of early diagnosis:

Babies with a positive genetic test (having biallelic pathogenic variants in the recessive forms or one pathogenic variant in heterozygosis in dominant forms) should be referred immediately to a paediatric neurologist for clinical evaluation.

CK dosage or EMG can be helpful. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings.

CMS is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.

In some subtypes of CMS, a positive response to acetylcholinesterase (AChE) inhibitors may occur. Response to AChE inhibitors is usually assessed by a controlled/supervised trial of oral AChE inhibitors and monitoring of fatigable muscle weakness and obvious clinical symptoms (e.g., ptosis, bulbar weakness). Most CMS respond favourably to acetylcholine-esterase inhibitors; 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine or atracurium.

Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information:

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