What is Segawa Syndrome & How is it Treated?

Segawa Syndrome (SS) is a movement disorder, which is genetic in nature and commonly appears in early childhood, around the age of 6 to 8 years.¹ Symptoms of Segawa Syndrome consists of increased muscle tone, Parkinsonian characteristics which are usually absent after rest or during the morning time, and worsens as the day passes after the patient undergoes some exertion. Children having Segawa Syndrome are often misdiagnosed as having cerebral palsy. Segawa Syndrome is an extremely rare condition. Females more commonly have this syndrome than males.² Treatment with levodopa is effective in Segawa Syndrome.

Segawa Syndrome is also referred to as hereditary progressive dystonia with diurnal fluctuation, Segawa’s dystonia, Segawa’s disease and Dopamine-responsive dystonia (DRD).

Segawa Syndrome usually develops in one limb and often in one leg. Worsening of the dystonia results in clubfoot, which leads to tiptoe walking. When the patient is about 18 years old the symptoms of Segawa Syndrome can spread to all the four limbs. After this age, there is slowing of this disease and gradually symptoms of Segawa Syndrome get plateaued. Patient can also experience regression in the developmental milestones including mental as well as motor skills. If treatment for Segawa Syndrome is not started, then patient fails to thrive.

Other than the above symptoms of Segawa Syndrome, the patient also has symptoms of Parkinsonism, which can be relatively mild. Parkinsonism signs in Segawa Syndrome include bradykinesia (slowness of movement), stiffness, tremors, rigidity, postural instability and balance difficulties. About 25% of the patients also have hyperreflexia, especially in the legs. These symptoms resemble the symptoms of Parkinson’s disease.

Segawa Syndrome patients are relatively free of symptoms in the morning after a good night’s sleep; however, the symptoms of Segawa Syndrome become increasingly severe as the day progresses. For this reason Segawa Syndrome is also known as “progressive hereditary dystonia with diurnal fluctuations.” However, there can be some patients with Segawa Syndrome who do not have these diurnal fluctuations; therefore, this condition is also referred by other names by researchers.

As the patient suffering from Segawa Syndrome has clubfoot and tiptoe walking, there is excessive wear and tear seen at the toes of the footwear with very little wear on the heels. Patients with Segawa Syndrome may also suffer from low self-esteem, eating disorders and lack of energy. The patient also has sad facial expressions during childhood period.

Segawa Syndrome patient will have an almost normal handwriting at the age of 3 to 5 years. Around pre-teens, i.e. around the ages of 8 to 11 years, patient will have poor handwriting. The handwriting becomes very worse during adolescence and extremely bad during post-teen period and the handwriting continues to worsen as the patient reaches adulthood and beyond.

• Segawa Syndrome is a rare condition due to which it often gets misdiagnosed as cerebral palsy and this results in the patients spending their complete childhood without starting any appropriate treatment for this condition.
• Diagnosis of Segawa Syndrome can be made from medical history of the patient, genetic testing and a trial of dopamine medications. Genetic defect may not be present in all the patients, so genetic testing is not completely reliable.
• A lumbar puncture can also be done to measure the amount of biopterin and neopterin. This will help in determining the exact type of dopamine-responsive movement disorder. If the biopterin is reduced and the neopterin is normal, then it indicates an early onset Parkinsonism. If both are decreased, then it indicates GTP cyclohydrolase-1deficiency. If both are normal then it indicates tyrosine hydroxylase deficiency.
• During a polysomnography (sleep study), Segawa Syndrome patient may have decrease in the twitching during REM phase of sleep.
• Imaging tests such as MRI scan of the brain helps in differentiating other conditions that resemble Segawa Syndrome. PET scan can also be done to differentiate Segawa Syndrome from other conditions.
• Differential diagnoses also consist of metabolic disorders (Phenylketonuria, GM2 gangliosidosis, hypothyroidism, Leigh syndrome), autosomal recessive early onset Parkinsonism with diurnal fluctuation, primarily dystonic juvenile parkinsonism, focal dystonias, early onset idiopathic parkinsonism, dystonia musculorum deformans and sandifer syndrome with hiatal hernia.
• A patient with suspected Segawa Syndrome is referred to a specialist or neurologist where the patient will be kept under a 24-hour day-cycle observation in the hospital to observe the typical diurnal affect of this condition. Patient is also told to walk around in the hospital at pre-determined daytime intervals, so that the worsening walking pattern along with increased muscle tension in the limbs can be observed. Other things which the doctor observes in a patient include the reducing leg-gait.

Treatment with levodopa is very effective in patients with Segawa Syndrome.³ There is a dramatic improvement in the symptoms of the patient with Segawa Syndrome with even low-dose levodopa. Patient can have almost a complete reversal of the associated symptoms of Segawa Syndrome and the effectiveness of this treatment is often long term and does not have the complications, which occur with treatment of Parkinson’s disease using levodopa. Therefore, some researchers think dopamine-responsive dystonia is an appropriate alternative name for Segawa Syndrome.

As Segawa Syndrome is often misdiagnosed, this condition often goes untreated and patients commonly need Achilles tendon surgery when they have reached adulthood. Patient has severe problems with walking, which worsen as the day progresses. Resting or napping gives temporary relief in patients without proper treatment. Segawa Syndrome also hinders growth, affects balance and decreases the muscle development in the calves. Patient also suffers from psychological problems such as depression, low self esteem, eating disorders, lack of social skills, along with difficulty in finding employment.

Currently, there is no data available regarding the death rate with Segawa Syndrome. With treatment Segawa Syndrome patients have known to survive beyond 50 years of age. However, if the Segawa Syndrome patient is suffering from severe, early autosomal recessive type of this disorder then patients tend to die during childhood. Girls are more affected with this condition and this syndrome usually starts during puberty or after the patient has reached the age 20. In rare cases, this syndrome can start in older adults also.

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