congenital myasthenic syndrome 17

Congenital Myasthenic Syndrome 17 (CMS17)

Congenital Myasthenic Syndrome 17, also known as CMS17, is a rare genetic disorder that affects the neuromuscular junction. It is characterized by failure of neuromuscular transmission, which leads to muscle weakness and fatigue.

Key Features:

• Muscle weakness that worsens with physical activity
• Failure of neuromuscular transmission
• Pre-synaptic, synaptic, and post-synaptic disorders not of autoimmune origin
• Typically identified at birth or in early childhood

Causes: CMS17 is caused by a mutation in the LRP4 gene (location: 11p11.2) [1]. This genetic defect affects the proper functioning of the neuromuscular junction, leading to muscle weakness and fatigue.

Symptoms:

• Fluctuating ptosis
• Bulbar symptoms
• Neck muscle and mild proximal limb muscle weakness
• Muscle weakness that worsens with physical activity

References:

[1] MONDO:0014578: OMIM ®: 616304: Definition. Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the LRP4 gene.

[2] Al Jabry T, Al-Hashmi N, Abdelhadi B, et al. LRP4 site-specific variants in the third β-propeller domain causes congenital myasthenic syndrome type 17. Eur J Med Genet 2024; 67:104903.

Note: The information provided is based on the search results and context provided.

Muscle Weakness and Fatigue

Congenital myasthenic syndromes (CMS) are characterized by muscle weakness that worsens with physical exertion, also known as fatigable weakness. This is the cardinal symptom of all myasthenic disorders.

• Muscle fatigue and weakness triggered by physical activity [2]
• Decreased movement in the womb [7]
• Stiff joints (arthrogryposis), reduced movements, a weak suck and cry, difficulty feeding, swallowing, and possibly episodic breathing difficulties from birth [7]

The severity of signs and symptoms vary greatly, from minor weakness to life-threatening symptoms like breathing difficulties. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations can occur.

• Muscle weakness that gets worse with physical activity [10]
• Fatigable weakness involving ocular, bulbar, and limb muscles [11]

It's essential to note that the signs and symptoms of congenital myasthenic syndrome can range from mild to severe and may get worse over time or only occur periodically.

• Symptoms range from mild to severe muscle weakness and may get worse over time or only occur periodically [10]
• Myasthenic symptoms may be mild, but sudden severe exacerbations can occur in some subtypes of CMS [11]

If you notice signs or symptoms common to congenital myasthenic syndromes, make an appointment with your doctor for proper evaluation and care.

• Make an appointment with your doctor if you notice signs or symptoms common to congenital myasthenic syndromes [12]

Diagnostic Tests for Congenital Myasthenic Syndrome (CMS)

Congenital Myasthenic Syndromes (CMS) are a group of rare genetic disorders characterized by muscle weakness that worsens with physical exertion. Diagnosing CMS can be challenging, but various diagnostic tests can help confirm the condition.

Genetic Testing

• Next-generation sequencing: This test detects single nucleotide and copy number variants in 28 genes associated with congenital myasthenic syndromes [3].
• 21 gene panel: This panel assesses non-coding variants and is ideal for patients with a clinical suspicion of CMS [4].
• Targeted testing: Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel [9].

Clinical Diagnosis

• History and physical examination: Clinical diagnosis may rely on history, clinical exams, blood tests, incremental or decremental responses, or abnormal single-fiber EMG (SF-EMG) study results [6].
• Blood tests: Blood tests can help identify the underlying cause of muscle weakness.

Other Diagnostic Tests

• Single-fiber EMG (SF-EMG): Abnormal SF-EMG study results can be indicative of CMS.
• Muscle biopsy: Muscle biopsy may be performed to rule out other conditions that may present with similar symptoms.

It's essential to

Treatment Options for Congenital Myasthenic Syndrome (CMS) Type 17

Congenital Myasthenic Syndrome (CMS) type 17 is a rare genetic disorder caused by variants in the LRP4 gene. While there are no licensed drugs specifically approved for CMS treatment, various medications have been used off-label to manage symptoms.

• LRP4 site-specific variants: Research has shown that β2-adrenergic receptor agonists can be effective in treating CMS patients with CHRNE mutations, particularly those with primary muscle weakness [1].
• β-adrenergic agonists: A meta-analysis revealed evidence supporting the use of salbutamol and ephedrine as first-line pharmacological treatments for CMS [2].
• Pyridostigmine (PD): This acetylcholinesterase inhibitor has been used to treat various types of CMS, including type 17. However, its effectiveness may vary depending on the underlying defect [3].
• Other therapeutic agents: Depending on the specific mutation and symptoms, other medications such as 3,4-diaminopyridine, quinidine sulfate, fluoxetine, and amifampridine have been used off-label to manage CMS type 17 [4].

It's essential to note that treatment for CMS type 17 is highly individualized and may require a multidisciplinary approach. A healthcare professional should be consulted to determine the most effective treatment plan.

References:

[1] Kediha MI (2024) - Congenital Myasthenic Syndromes: A Review of Treatment Options [5] [2] Shao S (2023) - Meta-Analysis of β-adrenergic agonists in CMS treatment [6] [3] Schara U (2008) - Therapeutic agents used in CMS depend on the underlying defect [7] [4] Thompson R (2019) - Systematic review of pharmacological treatment for each CMS type [8]

Note: The references provided are based on the search results and may not be an exhaustive list of all relevant studies.

Differential Diagnosis of Congenital Myasthenic Syndrome (CMS) Linked to Chromosome 17p

Congenital myasthenic syndromes are a group of rare genetic disorders that affect the transmission of nerve impulses to muscles, leading to muscle weakness and fatigue. One subtype of CMS is linked to chromosome 17p.

Key Features:

• Muscle weakness that worsens with physical activity [9]
• Ptosis (drooping eyelids) and ophthalmoparesis (weakness of eye muscles) are common symptoms [5]
• Generalized muscle weakness, including facial and bulbar weakness [5]
• Hypotonia (low muscle tone) in infants, leading to poor sucking and crying [6]

Differential Diagnoses:

• Seronegative autoimmune myasthenia gravis: CMS patients may be misdiagnosed with this condition due to similar symptoms [8]
• Other neuromuscular disorders, such as laryngomalacia, epilepsy, cardiac conduction defects, and congenital hypothyroidism [10]

Important Considerations:

• Early diagnosis is crucial for effective management and treatment of CMS
• A comprehensive diagnostic workup, including genetic testing, electromyography (EMG), and muscle biopsy, may be necessary to confirm the diagnosis

References:

[1] by AG Engel · 2007 · Cited by 125 — The Differential Diagnosis of Congenital Myasthenic Syndromes ... Congenital myasthenic syndromes linked to chromosome 17p ...

[8] by A Chaouch · 2012 · Cited by 53 — 4.1 Differential diagnosis of CMS.

[9] by K Ohno · 2023 · Cited by 55 — DOK7-CMS is recognized as limb-girdle CMS, but ocular, facial, and bulbar weakness is frequently observed.

[10] by G McMacken · 2018 · Cited by 52 — Differential diagnoses included laryngomalacia, epilepsy, cardiac conduction defects, congenital hypothyroidism, Prader–Willi syndrome and ...