Facioscapulohumeral muscular dystrophy (FSHD): genetics and living with it

The name describes where the weakness starts: face (facio), shoulder blade (scapulo) and upper arm (humeral). A person may be unable to whistle, close the eyes tightly or smile fully, and relatives may remark that the face looks less expressive. Shoulder weakness makes it hard to lift the arms above the head, and the shoulder blades can protrude like wings when the arms are raised.

Weakness is often asymmetric, with one side clearly worse than the other, which helps distinguish FSHD from many other conditions. Later, the abdominal muscles, hip girdle and the muscles that lift the front of the foot can be affected, causing foot drop and a tendency to trip.

On chromosome 4 there is a repeated block of DNA called D4Z4. In most unaffected people it contains between 11 and 100 repeats, and the surrounding DNA is tightly packaged, which keeps the DUX4 gene switched off in muscle. In FSHD1 the block is shortened to between 1 and 10 repeats, packaging relaxes and DUX4 activates when it should not. DUX4 is toxic to muscle cells.

FSHD2 produces the same end result by a different route. A change in the SMCHD1 gene, which helps keep D4Z4 tightly packaged, combines with a permissive form of chromosome 4. Because two separate genetic ingredients are needed, FSHD2 follows a different inheritance pattern from FSHD1. About 20 percent of people with FSHD2 have no identified SMCHD1 change, according to MedlinePlus.

FSHD1 is autosomal dominant. A child of an affected parent has a 50 percent chance of inheriting the shortened D4Z4. Severity cannot be forecast from the parent's experience: one relative may notice only mild shoulder weakness in their fifties, while another develops significant weakness in their teens. New changes can also arise without a family history.

Clinical genetics can explain whether relatives should be tested, and what a positive result does and does not predict. Genetic counselling is available alongside NHS testing, which is free when arranged by a hospital specialist.

A neuromuscular specialist usually recognises the pattern on examination. Standard blood tests may show a normal or mildly raised creatine kinase. Because the genetic mechanism is unusual, standard sequencing panels do not detect FSHD1, which requires a specific test of the D4Z4 region. If a clinician is convinced of FSHD but the first test is negative, FSHD2 testing is considered.

MRI of the muscles can show characteristic patterns of involvement and may be used when the diagnosis is uncertain. The NHS lists blood tests, genetic screening, electromyography, muscle biopsy and MRI among the tools used in muscular dystrophy generally.

No treatment currently reverses FSHD, and management is individually tailored. Physiotherapy encourages regular low-impact activity and maintains range of movement. Occupational therapy advises on shoulder-sparing techniques at work and at home. Ankle-foot orthoses can help foot drop. Back and shoulder pain are common and managed with physiotherapy and conventional pain strategies.

Some people have eye changes, with small retinal blood vessel abnormalities seen on eye examination, and some have hearing loss, particularly in early-onset disease, so an eye and hearing review is sometimes offered. Breathing muscles can be involved in a minority, so lung function tests are done when symptoms or severity suggest it. Surgical scapular fixation is occasionally considered in selected people with severe shoulder weakness and is a specialist decision.

FSHD is usually slowly progressive and often has little effect on life expectancy. MedlinePlus states that about 20 percent eventually require a wheelchair, so most people stay on their feet. The earlier the symptoms start and the larger the facial and shoulder involvement, the greater the likely impact, but the range is wide.