Congenital myopathy

Overview

Congenital myopathy is a rare genetic condition that affects muscles and is present from birth. It can cause muscle weakness in babies. This condition can lead to various problems, including skeletal issues like weak or improperly positioned bones, difficulties with breathing, and feeding challenges. Symptoms can appear right after birth, during infancy, or as the child grows.

There are six main types of congenital myopathy, each with its own set of symptoms, severity levels, treatment options, and outcome:

• Central core disease: This type of myopathy causes babies to be floppy (have low muscle tone) when they’re born. Children with this condition may have a delay in reaching developmental milestones and moderate weakness in their arms and legs. However, the weakness doesn’t tend to get worse over time. Central core disease is usually caused by a mutation in the RYR1 gene.
• Minicore (multicore) disease: Minicore disease is another type of core myopathy with several subtypes. Most of these subtypes result in severe weakness in the arms and legs and often cause a curved spine (scoliosis). Breathing difficulties and weakened eye movements are common. This condition can be caused by a mutation in the RYR1 gene or other genes.
• Nemaline myopathy: Nemaline myopathy is another common congenital myopathy. Babies with this condition often have problems with breathing and feeding. They can also have weakness in their face, neck, arms, and legs. Some may develop complications like scoliosis. Mutations in genes like NEM2, ACTA1, and TPM2 can cause nemaline myopathy.
• Centronuclear myopathy: This is a very rare type of congenital myopathy. It leads to weakness in a baby’s arms, legs, and face, along with drooping eyelids and eye movement problems. Weakness tends to worsen over time. Centronuclear myopathy can be caused by mutations in genes like DNM2, BIN1, or RYR1.
• Myotubular myopathy: Myotubular myopathy is a rare congenital myopathy that mainly affects male babies. It causes severe floppiness and weakness, along with breathing and swallowing difficulties. Many children with this condition do not survive their first year of life. Myotubular myopathy is typically caused by a mutation in the MTM1 gene.
• Congenital fiber-type disproportion myopathy: This is a rare condition that begins with floppiness. Symptoms include weakness in the face, arms, and legs, as well as breathing difficulties. Most infants with this condition are severely affected, but their ability to breathe may improve as they grow. Mutations in genes like TPM3, ACTA1, TPM2, MYH7, or RYR1 have been found in children with congenital fiber-type disproportion myopathy.

Symptoms

Congenital myopathy can manifest with varying symptoms, which can be present from birth or develop during infancy and childhood. Common signs include:

• Hypotonia: Reduced muscle tone and potential progressive loss.
• Muscle weakness: Typically affecting proximal muscles, such as those in the neck, shoulders, and pelvis.
• Breathing difficulties: Weak respiratory muscles may lead to breathlessness.
• Developmental delays: Milestones such as sitting up or turning over may be delayed.
• Feeding challenges: Difficulties with sucking, spoon-feeding, chewing, and drinking.
• Balance issues: Toddlers may experience falls or stumbling due to muscle weakness.

Causes

Most congenital myopathies are the result of mutations in specific genes, which affect the muscles, the nerves responsible for muscle stimulation, and the brain in children, leading to various health issues.