congenital myasthenic syndrome 2C

Congenital Myasthenic Syndrome 2C (CMS2C): A Rare Autosomal Recessive Condition

Congenital myasthenic syndrome 2C (CMS2C) is a rare autosomal recessive genetic condition associated with early-onset muscle weakness. This disorder affects the postsynaptic neuromuscular junction, leading to impaired neuromuscular transmission.

Key Features:

• Early-onset muscle weakness: CMS2C typically presents at birth or in early childhood, with symptoms ranging from mild weakness to severe muscle impairment.
• Variable severity: The severity of signs and symptoms can vary greatly among individuals, even within the same family.
• Autosomal recessive inheritance: CMS2C is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Clinical Presentation:

The clinical picture of CMS2C can be similar to that of myasthenia gravis, with individuals experiencing fatigable weakness involving ocular, bulbar, and limb muscles. However, the symptoms of CMS2C typically start at or shortly after birth, rather than in adulthood as is usual for myasthenia gravis.

Treatment:

While there is no cure for CMS2C, treatment options are available to manage symptoms and improve quality of life. Cholinesterase inhibitors, such as pyridostigmine, may be used to alleviate muscle weakness and fatigue.

References:

• [9] describes CMS2C as a rare autosomal recessive genetic condition associated with early-onset muscle weakness.
• [10] provides a detailed description of congenital myasthenic syndrome 2C, highlighting its characteristics and clinical presentation.
• [14] discusses the use of ch

Muscle Weakness and Fatigue

Congenital myasthenic syndrome (CMS) type 2C is characterized by muscle weakness and fatigue that worsens with physical activity. This can manifest as difficulty moving or maintaining posture, especially in the proximal muscles of the limbs [9][10].

Neonatal Symptoms

In some cases, CMS type 2C may present with symptoms during fetal development, such as decreased movement and increased amniotic fluid (polyhydramnios) [14]. After birth, affected infants may experience stiff joints (arthrogryposis), reduced movements, a weak suck and cry, difficulty feeding, swallowing, and possibly episodic breathing difficulties [14].

Early Childhood Symptoms

As children with CMS type 2C grow, they may exhibit delayed motor milestones, such as crawling or walking. They may also fatigue easily and have difficulty keeping up with their peers [8]. In some cases, symptoms may not be apparent until childhood or early adulthood.

Other Possible Symptoms

Additional signs and symptoms of CMS type 2C may include:

• Droopy eyelids (ptosis)
• Double vision or a lazy eye
• Difficulty talking or swallowing
• Limited or lack of muscle regulation

It's essential to note that the severity and presentation of symptoms can vary greatly among individuals with CMS type 2C, even within the same family [3]. If you suspect someone may have congenital myasthenic syndrome, it's crucial to consult a healthcare professional for proper diagnosis and care.

Diagnostic Testing for Congenital Myasthenic Syndrome 2C

Congenital Myasthenic Syndrome 2C (CMS 2C) is a rare genetic disorder that affects muscle strength and function. Diagnostic testing plays a crucial role in confirming the clinical diagnosis of CMS 2C.

• Genetic Testing: Genetic testing of specific genes, such as CHRNB1, may help confirm a clinical diagnosis of CMS 2C [3]. This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 28 genes associated with congenital myasthenic syndromes [4].
• Clinical Diagnosis: Clinical diagnosis may rely on history, clinical exams, blood tests, incremental or decremental responses, or abnormal single-fiber EMG (SF-EMG) study results [10].

Available Diagnostic Tests

Several diagnostic tests are available for CMS 2C:

• The Blueprint Genetics Congenital Myasthenic Syndromes Panel (test code NE1701) includes genes identified through literature, OMIM, and HGMD searches that have a reported association with CMS [6].
• Diagnostic testing for DOK7 mutations is now routine for patients with suspected CMS, including those with CMS 2C [8].

Importance of Early Detection

Early detection of symptoms through diagnostic testing can facilitate early intervention and improve disease prognosis and progression. Genetic testing may also help predict disease prognosis and progression [3].

Treatment Options for Congenital Myasthenic Syndrome (CMS) Type 2C

Congenital Myasthenic Syndrome (CMS) type 2C is a rare genetic disorder that affects neuromuscular transmission. While there are no specific treatments available, various pharmacological interventions can help manage symptoms and improve muscle strength.

• Acetylcholinesterase inhibitors: These medications, such as pyridostigmine, can be used to increase the concentration of acetylcholine at the neuromuscular junction, thereby improving muscle contraction. However, their effectiveness may vary depending on the underlying genetic defect [4][5].
• β-adrenergic agonists: Salbutamol and ephedrine have been shown to be effective in treating CMS type 2C, particularly in patients with mutations in the DOK7 gene [9]. These medications can help improve muscle strength and reduce symptoms.
• Other treatments: In some cases, other pharmacological agents such as quinidine sulfate, fluoxetine, or physiotherapy may be used to manage symptoms and improve quality of life. However, these treatments are typically reserved for patients with more severe forms of the disease [7][8].

It's essential to note that treatment options for CMS type 2C can vary depending on the specific genetic defect involved. A thorough diagnosis and consultation with a specialist are crucial in determining the most effective treatment plan.

References: [4] Lashley D, Palace J, Jayawant S, Robb S, Beeson D. Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7. Neurology. 2010;74(19):1517-1523. [5] Chaouch A, Muller JS ... [9] by R Thompson · 2019 · Cited by 60 — AChE inhibitors such as pyridostigmine are commonly used in patients with AChR deficiency, most of which are caused by biallelic mutations in ...

The differential diagnosis of congenital myasthenic syndrome (CMS) involves a wide range of conditions that can present with similar symptoms to CMS. Some of the key differential diagnoses for CMS include:

• Congenital myopathies: These are a group of rare, inherited muscle disorders that can cause weakness and fatigue in affected individuals [6].
• Autoimmune myasthenia gravis (MG): This is an autoimmune disease that causes muscle weakness and fatigue due to the production of antibodies against the acetylcholine receptor [7].
• Muscular dystrophy: A group of inherited disorders that cause progressive muscle weakness and degeneration [9].
• Mitochondrial myopathy: A rare, inherited disorder that affects the mitochondria in muscle cells, leading to weakness and fatigue [9].

It's worth noting that the differential diagnosis for CMS can be complex and requires a thorough evaluation of clinical features, laboratory tests, and family history. A suspected diagnosis is often based on typical clinical features, decremental responses of 10% or more on repetitive nerve stimulation (RNS) and/or abnormal jitter and block on single-fibre EMG [13].

In terms of specific conditions that can be misdiagnosed as CMS, a study found that the main misdiagnoses were congenital myopathy (50%), autoimmune MG (29.0%), muscular dystrophy (15.9%) and mitochondrial myopathy (8.7%) [9].