Nemaline Myopathy

Written by Dr.Paola Nicolaides, Consultant Paediatric Neurologist, for the Muscular Dystrophy Campaign

What is a myopathy?

The term myopathy is derived from the Greek language and it means muscle disorder.

What is a congenital myopathy?

The congenital myopathies are a group of conditions causing muscle weakness and wasting. Sometimes symptoms are present at birth but at other times they are not recognised until later on in childhood or adult life.

What is nemaline myopathy?

The name ‘nemaline myopathy’ was initially suggested in 1963 and refers to the tiny rod-like structures seen in the affected muscle fibres, which look like tiny threads (‘nemaline’ comes from the Greek word which means thread).

How does the disease present?

Like many other congenital myopathies, nemaline occurs in two main forms, with the severest form presenting at birth or even ante-natally, in contrast to the milder form which presents later on in childhood.

In the severe early onset form the baby may appear very hypotonic (floppy and weak) at birth and may have swallowing and breathing difficulties, facial weakness (myopathic face) and a high arched palate. In this form, the baby may not survive more than a few weeks or months of life, and will need immediate resuscitation at birth.

Most cases, however, present later on in childhood or adult life with a mild non-progressive or slowly progressive muscle weakness which may affect the face and muscles of the arms and legs. Abnormalities such as “pigeon chest”, “club feet” (pes cavus), “high arched palate”, an unusually long face and curvature of the spine (kyphoscoliosis) may be seen in this form.

Are patients at risk of developing any complications?

Children with nemaline myopathy are at increased risk of respiratory infections and in some cases sleep studies may be required to assess the child’s respiratory status and their respiratory function needs to be adequately monitored.

Very occasionally children may have cardiac symptoms.

Constipation may be a feature of the disease and may be caused by lack of exercise and insufficient mobility. Hearing, vision and intelligence are usually unaffected.

Is nemaline myopathy inherited?

Yes, usually. There are different patterns of inheritance. These are known as autosomal recessive, autosomal dominant and some cases are thought to be sporadic (a one-off with little risk of other children in the family being affected). The most common mode of inheritance is the autosomal recessive.

In the severe form of the disease in which case the patients present in early neonatal life, the inheritance is also thought to be autosomal recessive.

In autosomal recessive inheritance both parents need to be carriers of the condition, and the risk of a child of either sex being affected is 25% (one in four).

In the autosomal dominant inheritance, one (either) of the two parents is affected, may be only mildly so, but each child (of either sex) of the affected parent has a 50% (one in two) chance of being affected.

Recent genetic advances in nemaline myopathy

There have been some exciting new developments in the genetics of the congenital myopathies. This has been very helpful in offering us further understanding of this group of disorders and hopefully offers families possible treatment options in the future.

A number of gene abnormalities have been identified in patients with nemaline myopathy.

One of these genes is called the nebulin gene. It is sometimes faulty in the autosomal recessive form of the disease. This gene lies on chromosome 2 and is responsible for the production of a protein called nebulin necessary for the correct functioning of the muscle. If the gene is faulty it results in reduced production of the related protein known as nebulin. A number of mutations (gene faults) have been identified in patients with nemaline myopathy.

The other genes identified to be related to nemaline myopathy are the tropomyosin (TPM) and the alpha actin genes (ACTA1). The tropomyosin gene lies on chromosome 1 and again, a number of different mutations have been identified in different families. The ACTA1 gene defects cause wide abnormalities in the development of skeletal muscle.

In the very severe form of nemaline myopathy which presents in the newborn baby with almost total lack of movement in the arms and legs and very weak chest muscles the genetic defect has not been fully identified, although abnormalities in the above genes have been described in some infants. These babies who may also have contractures (limb deformities) at birth are usually permanently ventilator dependent. This is a small, unique group and the prognosis in these cases is generally poor.

Similarly, the gene abnormalities have not been fully defined for the adult-onset nemaline myopathies.

Studies of further families are needed to identify the remaining causative genes.

How is nemaline myopathy diagnosed?

The diagnosis of a “myopathy” is usually suspected from the history and examination. However the specific diagnosis of nemaline myopathy is nearly always made by looking at a piece of muscle (muscle biopsy). Before doing a muscle biopsy (which involves taking out a small piece of muscle usually from the thigh muscle) a few other tests may be done, one of which is a blood test which measures the level of a muscle enzyme (creatine kinase or CK level), which is usually normal but which may be slightly raised.

The other is an electrical test of the muscles and the nerves supplying the muscle. This test involves placing a fine needle into the muscle which then measures the electrical activity arising from that muscle. Although this test may be able to show a “myopathic” pattern of abnormal muscle activity (seen in any myopathy) it is unable to define the exact type.

The muscle biopsy is therefore the important test which will make the diagnosis by demonstrating the thread or rod-like structures within the muscle fibres. The number of rods may vary and in some cases the whole muscle fibre may be involved, whereas in other cases only a few fibres may show the characteristic rods.

Is the condition progressive?

The rate of progression of the condition is variable. In general the earlier the onset, the more severe the disorder is. In most cases the disease is only slowly progressive.A few patients may eventually lose the ability to walk. Occasionally muscle weakness may progress quite rapidly and these patients experience serious breathing problems.

Is there a treatment or a cure?

At the moment, there is no cure, nor any drug treatment for nemaline myopathy. However, other very helpful measures can be taken, such as physiotherapy, the use of antibiotics to treat chest infections, or naso-gastric tube feeding when necessary.

What help can be offered?

Physiotherapy is one of the main forms of help. An initial physiotherapy assessment at the time of the diagnosis should be followed by an exercise programme and regular check-ups. The main aim of physiotherapy is to keep the muscles as active as possible to prevent the formation of ‘contractures’ (muscle tendon tightness causing restriction in the range of joint movement). It is also important to provide good seating and to ensure a proper sitting and standing posture to prevent scoliosis (curvature of the spine). The other role of physiotherapy is to help with provision of appliances, such as splints, calipers, standing frames (mechanical aids helping to keep children on their feet) and wheelchairs where necessary. Children and adults are encouraged to remain as active as possible and ensure that they do not become overweight, so that the strain imposed on their weak muscles is kept to a minimum. Swimming is a particularly good form of exercise.