This term refers to a particular rare type of genetic muscle disease that presents with muscle weakness which typically becomes apparent in infancy or early childhood (congenital) and can worsen quickly. It is caused by genetic faults in a gene called LMNA.
LMNA-related congenital muscular dystrophy (L-CMD) primarily affects the muscles used for movement (skeletal muscles). Thus affected individuals have low muscle tone (hypotonia) and muscle wasting (atrophy), typically beginning very early in life (in infancy). The clinical features can, however, vary considerably in different families. The most severely affected infants are never able to hold up their heads, roll over, or sit. Less severely affected children may learn to sit, stand, and walk before muscle weakness develops. There may be delays in children reaching their motor milestones such as sitting or standing unassisted. They may then lose some of these skills as the disease progresses. Spinal stiffness and abnormal curvature of the spine (scoliosis and lordosis) may also develop. Thickening and shortening of tissue such as muscle fibres develop, especially across joints. This restricts movement and cause deformity (contractures). Over time most infants and children with L-CMD have trouble eating and breathing due to weakness of the chest muscles. This problem can be life threatening, and many affected children require support with a machine to help them breathe (mechanical ventilation).
Some individuals with genetic faults in LNMA may present only with muscle weakness in a limb-girdle distribution in adulthood, with much milder weakness, and thus LMNA-related myopathies represent a continuum with a broad range in age of onset but overlapping clinical features. The heart muscle may also be involved. Heart involvement may precede onset of muscle weakness or may sometimes be isolated.
A child with L-CMD is usually the only person in the family to have the condition. A so-called “de novo mutation” had arisen in the sperm or egg from which they developed. The risk of parents having a second affected child is thus very low, although it may not be zero. The adult onset form is inherited in an autosomal dominant manner. This means that an affected parent has a ½ or 50% chance of passing the condition on to a child. Although individuals in a family may have quite variable features, a more mildly affected adult would not be expected to have a child with CMD.