Centronuclear and nemaline myopathies: structural congenital myopathies

Congenital myopathies differ from muscular dystrophies in that the muscle fibres are structurally abnormal but are not usually undergoing active breakdown and repair. Creatine kinase is therefore often normal or only mildly raised. Babies are typically floppy with weak feeding and cry, and older children may have a long, narrow face, a high arched palate and a slender build.

They are named after the finding in a muscle biopsy: rods (nemaline), nuclei in the centre of fibres (centronuclear), cores, or an uneven spread of fibre types. Genetic testing now supplements or replaces the biopsy, but the original names persist.

MedlinePlus describes progressive weakness particularly in facial, neck and trunk muscles, and rod-like structures called nemaline bodies seen under the microscope. Rods are visible on a Gomori trichrome stain. The disease is classified into six types by severity, from a severe congenital form, often fatal in early childhood, to an adult-onset form that is the mildest. The typical congenital type is the most common, with feeding difficulties in infancy but generally unassisted walking later.

Features include weak swallowing and cough, scoliosis, joint deformities and foot problems. Severe cases involve respiratory compromise. The disorder is usually autosomal recessive, with less common autosomal dominant cases, often from new mutations. Mutations in NEB and ACTA1 disrupt the organisation of proteins in sarcomeres, impairing contraction.

MedlinePlus lists DNM2, BIN1 and TTN as the most common genetic causes, with DNM2 following an autosomal dominant pattern and TTN and most BIN1 changes autosomal recessive. Features include weakness and wasting in skeletal muscles from birth through early adulthood, droopy eyelids, facial weakness and a distinctive microscopic finding of nuclei displaced to the centre of the muscle cell rather than lying at the edge.

Some patients have limited eye movements as well as drooping lids, which can cause double vision. Course varies considerably. Most people show slow worsening and some need respiratory support, but MedlinePlus notes that, in rare instances, weakness improves over time. X-linked myotubular myopathy is a related condition with a different gene and a more severe presentation in boys.

Paediatric or adult neuromuscular teams assess the pattern of weakness, facial involvement and respiratory function. Muscle MRI patterns, creatine kinase and EMG help narrow the field. A muscle biopsy remains useful because the structural finding guides the choice of genes, and the NHS lists muscle biopsy among tools used for muscular dystrophy and related diagnosis.

Gene panels or exome and genome sequencing through the NHS Genomic Medicine Service now often provide the answer. NHS genetic testing is free when arranged by a hospital specialist, and genetic counselling is provided alongside it.

No treatment currently corrects either condition, and care is supportive. Breathing is central: lung function tests, sleep studies and, where needed, cough assistance and non-invasive ventilation. Swallowing and feeding review prevent aspiration and malnutrition. Physiotherapy and orthoses maintain mobility, and the spine is monitored for scoliosis. Eyelid and eye movement problems are managed by ophthalmology.

Anaesthesia needs advance planning. Some congenital myopathies, particularly RYR1-related ones, are linked with malignant hyperthermia susceptibility, a rare anaesthetic reaction, so genetic results should be shared with surgical teams.

Because inheritance varies by gene, genetic counselling is particularly important. Recessive forms carry a 1 in 4 recurrence risk for siblings, and dominant forms carry an even chance for each child of an affected parent, with many dominant cases arising as new mutations. X-linked disease requires specific carrier assessment for female relatives.