Dopa-responsive dystonia: symptoms, diagnosis and treatment with levodopa

Dystonia is a neurological movement disorder in which muscles contract continuously or intermittently, producing abnormal, often painful, repetitive movements or postures. Dystonia UK describes dopa-responsive dystonia as a rare but highly treatable form of genetic dystonia. It is also known as Segawa disease, DYT5 dystonia and progressive hereditary dystonia, and the most common form is usually called DYT5.

The name reflects the key clinical feature. Dopamine is a chemical messenger that helps the brain produce smooth physical movement, and in this condition the brain makes too little of it. Giving a medicine that the body can turn into dopamine, levodopa, often restores movement to a remarkable degree. MedlinePlus Genetics estimates the condition affects about 1 per million people worldwide, although it is probably underdiagnosed because mild cases may not be recognised.

Dystonia UK says that in many people the first symptoms are in the feet and legs, and may later involve the arms and trunk. MedlinePlus Genetics says that the first signs are typically inward and upward turning feet and dystonia in the lower limbs, and that over time the whole body may become involved from adolescence.

• A stiff-legged way of walking, toe walking, upward bending of the sole of the foot or turning of the foot outward at the ankle.

• Muscle spasms and tremor.

• Signs of parkinsonism that may be relatively subtle: slowness of movement, stiffness and resistance to movement, balance difficulties and postural instability.

• Symptoms that fluctuate, worsening as the day progresses and improving in the morning after sleep.

• Stress and anxiety are known to make the symptoms worse, according to Dystonia UK.

• In some people, sleep problems or episodes of depression, which MedlinePlus Genetics says are more frequent than expected in some forms.

Dystonia UK explains that dystonia is caused by incorrect signals from the brain to the affected body part and that dopa-responsive dystonia is an inherited type caused by mutations in a specific gene that cause a problem with the brain's production of dopamine. MedlinePlus Genetics says mutations in the GCH1 gene are the most common cause, with less frequent changes in the TH or SPR genes. These genes are involved in the production of tetrahydrobiopterin and dopamine.

When the GCH1 gene is responsible, the condition is inherited in an autosomal dominant pattern, so one altered copy is enough. MedlinePlus Genetics says some people who inherit the altered gene never develop features of the condition, and Dystonia UK gives a figure of 30 to 40 per cent of gene carriers developing it. This explains why an affected child may have a parent with mild or no symptoms. Some people with the condition have no mutation found in the known genes.

Dystonia UK says dopa-responsive dystonia should be diagnosed and treated by a neurologist specialising in movement disorders. Diagnosis rests on the typical story of childhood-onset leg dystonia with diurnal fluctuation, examination for subtle parkinsonian signs, and the response to levodopa. A genetic counsellor can explain what genetic findings mean for the family.

Mild or atypical presentations are easy to miss, and MedlinePlus Genetics notes that the condition may be misdiagnosed in people whose symptoms resemble other movement disorders. A neurologist will weigh the pattern of symptoms and the response to treatment together.

Dystonia UK lists oral levodopa (Sinemet) and physiotherapy as the common treatments, and says full physical functionality can typically be restored through the use of levodopa. Physical therapy may help if walking problems have been identified or if muscles have shortened while the condition was uncontrolled.

Because the underlying difficulty is a lack of dopamine, treatment is usually long term. The dose and timing are managed by a neurologist. MedlinePlus Genetics notes that the movement difficulties associated with the condition usually worsen with age but stabilise around age 30, which is one reason early recognition matters.

Dystonia UK says you may need to find ways to adapt and learn new ways of completing everyday tasks, but it is possible to live well with the condition. It also says that because this form may be genetic, some people find it helpful to speak to a genetic counsellor about what it means for them and their family. In a UK context that is usually arranged through a clinical genetics service, referred from neurology or by a GP.

Dystonia UK lists physiotherapy among the treatments and says it supports people at all stages, including onset, diagnosis and finding treatment.