CNM is a non-progressive, or slowly progressive, condition. For babies born with XLMTM, however, the condition may progress rapidly into respiratory failure leaving most needing respiratory support for at least some hours of the day or night. The autosomal forms are usually less severe, with few notable exceptions.
X-linked myotubular myopathy (or XLMTM)
This is the most severe form of centronuclear myopathy. It usually affects only males, and has the earliest onset. Often, but not always, there are signs of the condition before the baby is born. These can include reduced foetal movement and often an excessive accumulation of amniotic fluid around the baby. Most individuals with XLMTM are born with severe floppiness (hypotonia) and muscle weakness. Infants may fail to breathe spontaneously at birth and most will require breathing support. There are usually problems with feeding, in particular swallowing, and persistent breathing problems. Chest infections may occur frequently because of a weak or non-existent cough function.
A child with XLMTM may appear to have a long face, and it can seem expressionless. Their eyelids may be puffy, and some of the muscles in the eyes may not work well, so they are unable to move or close their eyelids fully. There may also be tightening (contractures) of the knee and ankle joints.
The severity of the condition varies considerably among individuals. Some may not survive the first few months of life, and those who do may show improvement in the first few years, and then may become severely disabled. Many will require ventilation to support their breathing. Occasionally, some improve significantly and experience only mild weakness even into adulthood. For those requiring breathing support from birth or early in life, this is unlikely.
Autosomal dominant CNM
Onset of this form is variable, ranging from birth to adulthood. It usually presents later than in other forms of CNM and generally, it is not as severe as XLMTM. The condition usually follows a mild course. There is weakness in the muscles closest to the trunk of the body, although some may experience weakness in other muscles. It is important to monitor heart and lung function, although involvement of these organs is rare.
Autosomal recessive CNM
With onset occurring in infancy or early childhood, this form can vary considerably in severity: from XLMTM-like, to later onset and milder variants. Weakness of the muscles in the face can be common, as can droopiness of the eyelids and limitation of eye movements. Some may have problems with feeding and/or breathing, occasionally requiring a feeding tube and/or breathing support. There is usually weakness of the muscles closest to the trunk of the body (known as axial and proximal muscles).
A number of different genes are associated with this form of CNM, with mutations in the RYR1 gene being the most common cause. Individuals with mutations in the TTN gene can often have curvature of the spine (scoliosis) and/or stiffness of the spine (rigid spine). Cardiac disease (cardiomyopathy) can affect people with mutations in the TTN or SPEG10 genes. Cardiac monitoring is therefore recommended in individuals affected by these specific forms of centronuclear myopathy.