Distal myopathies: muscle disease that begins in the hands and feet

People with a distal myopathy may notice that jar lids and keys have become hard to manage, that fingers do not extend well, or that the front of the foot catches on kerbs. Some are first aware of changed calf shape. Others are diagnosed after tripping repeatedly or having a footwear problem that does not resolve.

The key clinical question is whether the problem is in the muscle or the nerve. Both can produce distal weakness, and a neurologist will look for sensory loss, reflexes, high arches and family history, since nerve diseases such as Charcot-Marie-Tooth disease often bring numbness and foot deformity as well. Electrical studies separate the two.

GNE myopathy, also known as hereditary inclusion body myopathy or Nonaka myopathy, illustrates the group. MedlinePlus describes difficulty lifting the front of the foot, due to weakness of the tibialis anterior muscle, as the first sign. Over time weakness spreads to the upper legs, hips, shoulders and hands. A distinctive feature is that the quadriceps are usually spared, which differs from most myopathies. The eyes and heart are not affected, and there are no neurological problems.

Symptoms emerge in late adolescence or early adulthood and slowly worsen. MedlinePlus states that most individuals require a wheelchair within 20 years after symptoms appear. The GNE gene encodes an enzyme involved in sialic acid production, and researchers are still working out precisely how a shortage of sialic acid leads to progressive weakness.

Other forms differ in which muscles go first and how quickly. Dysferlin-related distal myopathy, often called Miyoshi myopathy, typically begins in the calves and is associated with very high creatine kinase levels. Others, caused by genes such as MYH7, TTN, DES or ZASP, can start in the hands or the anterior lower legs and may be dominant, with the heart sometimes involved.

Because several genes produce overlapping pictures, diagnosis relies on a combination of clinical pattern, muscle MRI and a genetic panel. Some forms involve rimmed vacuoles on muscle biopsy, others show different non-specific changes.

The NHS lists blood tests, genetic screening, electromyography, muscle biopsy and MRI as the main tests used for muscular dystrophy generally, and the same toolkit is used here. Creatine kinase is normal to mildly raised in some forms and very high in others. Nerve conduction studies and EMG show whether the nerve or muscle is the origin. MRI of the lower legs often shows patterns of fatty replacement that point to specific genes.

Genetic panels are available through the NHS Genomic Medicine Service, and NHS genetic testing is free when arranged by a hospital specialist. Because the genes are numerous and variable, a negative panel does not exclude a distal myopathy.

Management is supportive. Ankle-foot orthoses and well-fitted footwear address foot drop and reduce falls. Hand therapy and adaptive equipment help with fine tasks. Physiotherapists advise on safe exercise. Heart review is added where the gene is known to affect cardiac muscle, and respiratory review where breathing muscles may be involved.

Clinical trials are being run for some forms, particularly GNE myopathy, but no treatment that corrects the underlying cause is available through routine NHS care, and nothing here should be read as a promise of treatment.

GNE myopathy and dysferlin-related disease are autosomal recessive, so parents of an affected person are usually unaffected carriers, with siblings having a 1 in 4 chance of being affected. Other distal myopathies are autosomal dominant and an affected parent has an even chance of passing the gene on. Clinical genetics can explain the pattern in a given family.