Putting Brains in Muscles

Towards an Accessible Web-Based Health Education Platform on Neuromuscular Diseases

Congenital Myopathy

What is Congenital Myopathy?

Congenital myopathy (CM) is a group of rare hereditary muscle diseases caused by underlying genetic mutations. ‘Congenital’ means early onset of symptoms that either at birth, during infancy or childhood age.

The major presenting symptoms are muscle weakness and hypotonia. More severely affected infants may appear weak and floppy, and frequently also have breathing difficulty and feeding and swallowing problems. These infants’ motor milestones are delayed, and they often cannot roll over or sit up at the expected time. Facial muscle weakness and limitation of eye movement are also common. For children or individuals who are only mildly affected, weakness mainly affects the muscles of the proximal shoulder and hip girdles; when performing motor activities such as raising arms, getting up from squatting, going up and down stairs, or fast walking, they may easily feel tired or exhausted. Some affected children or individuals also have musculoskeletal problems such as scoliosis, hip subluxation and dislocation, and contractures and deformities of other joints. Sometimes, due to breathing muscle weakness, they also have breathing difficulties.

How are Congenital Myopathies diagnosed?

Your doctor will take a detailed history asking you about the onset of your child’s symptoms and how the disease has progressed over time. If your child is suspected to have congenital myopathy, further testing will be needed to confirm the diagnosis. Muscle enzymes (Creatine Kinase level) will be checked and electromyography study will be arranged. Muscle biopsies provide helpful clues on the possible subtype of congenital myopathy to guide the genetic testing.

Based on the muscle biopsy findings, the congenital myopathy can be classified into different subtypes. The more common subtypes are:

  • Central core myopathy
  • Multi-minicore myopathy
  • Nemaline rod myopathy
  • Centronuclear myopathy
  • Myotubular myopathy
  • Congenital myopathy with fiber type disproportion
  • Hyaline body myopathy

Each affected individual will have different presenting symptoms with different severity. For example, some subtypes of congenital myopathy often have early onset of severe weakness with early development of respiratory, joints and spinal problems. Other subtypes may have associated cardiac problem.

What is the prognosis for Congenital Myopathies?

Congenital myopathies do not usually have a progressive disease course, so the prognosis is typically better than that of congenital muscular dystrophy. The prognosis of different subtypes of congenital myopathies and each affected individual can be different because they have different presenting symptoms and severity. Mildly affected children or individuals, will only have mild gross motor delay at a young age and are able to attend school like other children and go to work when they grow up. On the other hand, more severely affected children may not be able to achieve sitting or walking. Some subtypes can also have earlier respiratory difficulty and even cardiac problem, and as the child grows, the spinal curve and the joint contractures increase too.

What is the available treatment?

Currently there is no curative treatment for congenital myopathy. However, the standard of care treatment should include a multi-disciplinary team to follow-up the affected individuals and to provide the therapy and intervention to improve their general health, performance and participation.

The affected individual should have regular follow-up by the multidisciplinary team. Upon each follow-up, the vital signs, growth, and nutritional status will be monitored. Other important regular evaluations include sleep study, lung function test, muscle strength test and motor function assessment. Affected individuals will be referred to the occupational therapist, physiotherapist, dietitian, and clinical psychologist for further recommendation of rehabilitation need and follow-up.

In more urgent situations, where affected individuals report respiratory difficulty, poor general states or appetite, unsatisfactory weight gain or weight loss, or develop seizures, the families or the affected individuals should seek early consultation. If the condition is critical, one should immediately go to the Accident and Emergency Department for treatment.

Musculoskeletal Care:The common muscles and skeletal problems include muscle weakness, joint contractures, joint deformities, joint subluxation or dislocation, and spinal curve (scoliosis). Both the physiotherapist and occupational therapist will provide information on regular stretching exercises, the use of splintage to prevent the rapid development of joint contractures, the use of rehabilitation equipment including assistive walking device and standing frame, and special seating arrangements. Sometimes, the children will need orthopaedic surgery to correct joint dislocation or significant scoliosis.

Pulmonary Care:Some affected children with congenital myopathy will develop early respiratory insufficiency due to significant respiratory muscle weakness. The deterioration of the spinal curve also compresses the chest wall further and deteriorates respiratory function. The doctor will arrange regular lung function tests to follow-up the breathing effort of the affected children and individuals. If there is evidence that clearance of sputum is becoming more difficult, or ventilation support is required, the therapists will also teach affected individuals and families on the daily chest physiotherapy and use of cough assist device. If the affected individual requires ventilation support, it usually starts with the use of a non-invasive ventilator for initial night time use during sleep. If the respiratory muscle weakness progresses, the time for the non-invasive ventilation support will be increased and occasionally, changing to invasive ventilation support with direct ventilation through tracheostomy may be considered. Individuals with congenital myopathy are more prone to developing respiratory complications during respiratory tract infection. Therefore, they are recommended to complete their immunization schedule and to receive yearly seasonal flu vaccination.

Nutritional Care:Because of the weak oral and pharyngeal muscles, individuals with severe congenital myopathy often have feeding and swallowing problems, therefore increasing the risk of poor nutrition and aspiration causing aspiration pneumonia. The doctor will arrange an assessment by a speech therapist and a swallowing study to assess the performance of oral feeding. The dietitian will also recommend necessary dietary modification to improve the nutritional intake. If it is unsafe to continue oral feeding, the child can receive his or her nutritional intake through a nasogastric tube (for short term use) or gastrostomy feeding.

Special Education:Apart from physical impairment, some children with congenital myopathy also have learning difficulties or related specific learning problems. The doctor will arrange a detailed assessment on their intellectual potential and may refer the child to the Education Bureau for special education support with necessary rehabilitation training support in school.

Psychological Care:Congenital myopathy is a chronic illness that can have negative psychological impact on the affected individuals. Family members who take care of the affected individual often have chronic stress. The doctor will refer the individual or the family member to a clinical psychologist for further psychological support and counseling if there is significant stress on the individual or the family.

Palliative Care:The purpose of the palliative care is to improve the quality of life of the affected child or individual through management approach that can decrease the painful experience of the affected. Pain management and psychological support are both very important to the affected and the family, especially in situations where the medical condition is critical.

Others:Congenital myopathy can also lead to other commonly seen problems such as gastroesophageal refluxes, constipation, poor oral hygiene and dental problems. The doctor will provide treatment according to each of the presenting problem.

Clinical Trials?

X-linked myotubular myopathy gene therapy clinical trial
The open-label Phase I/II trial, ASPIRO, will evaluate the safety and preliminary efficacy of a single dose of AT132, the viral vector that carry a functional copy of the MTM1 gene. Primary outcome will include respiratory and motor function parameters assessment and, as a secondary endpoint, muscle biopsy evaluation. The goal is to enroll 12 children under five years of age and test three different doses.

Can this condition be prevented at the future pregnancy?

Congenital myopathy is caused by genetic mutations. The inheritance can be of autosomal recessive, autosomal dominance or even X-linked recessive. The child can either get the mutation(s) from one or both of the parents, or develop the mutation himself or herself. If an underlying genetic mutation can be found in the affected child, and one or both of the parents have been confirmed as the carrier of the mutated gene, prenatal diagnosis and even pre-implantation genetic diagnosis can be arranged to ensure the next pregnancy is not affected.