Segawa Syndrome is a movement disorder that was first described by Segawa et al in 1971 in two female patients who happened to be cousins. In 1976 Segawa reported more such cases and described the condition as “hereditary progressive dystonia (HPD) with marked diurnal variations”, in other words, the condition ran in families and showed fluctuations of symptoms throughout the day. Segawa Syndrome is also known as Dopa-Responsive Dystonia, the term proposed by Nygaard, which is now used broadly for dystonia that responds to Dopamine therapy. In this article, we will learn about the cause, symptoms, diagnosis, and treatment of Segawa Syndrome.
What Causes Segawa Syndrome?
Segawa Syndrome is caused by genetic mutations. It involves the mutation of the GCH1 gene located in Chromosome 14. The GCH1 gene encodes the enzyme GTP Cyclohydrolase-1 which is required for the synthesis of dopamine from tyrosine and tetrahydrobiopterin. This leads to a decrease in the level of dopamine in the nigrostriatal neurons in the brain that are involved in controlling movement. This lack of dopamine ultimately results in the abnormal involuntary movements or dystonia that are seen in the condition, the symptoms of which are described below.
Is Segawa Syndrome a hereditary condition?
Yes, Segawa Syndrome can be inherited as well as sporadic (that is - no history of the condition in the bloodline of the affected individual). The condition can be inherited in Autosomal Dominant Pattern – where one of the parents is affected or Autosomal Recessive – where none of the parents are affected but both of them are carriers of the defective gene. Recessively inherited mutations of the GCH1 gene result in a more severe condition and are associated with developmental delays of the child as well. The syndrome also shows variable expressivity, that is different individuals with the same mutation can have a different level of severity as well as incomplete penetrance, which means some individuals even after inheriting the defective gene might not show any symptoms of the syndrome at all.
Segawa Syndrome Symptoms
The syndrome usually manifests in childhood, the symptoms may fluctuate throughout the day and have the following features:
- Symptoms usually start in one limb, typically the foot, and progresses to other limbs and parts of the body over 10-15 years if left untreated. The progression usually comes to a stop in the fourth decade of life.
- Clubfoot like posturing of the foot may be present due to muscle contraction
- Uncoordinated walking style due to involuntary contraction of the muscles or dystonia that results in frequent falls
- Handwriting is usually normal at the age of 3-5 years, but progressively worsens with time
- Signs of Parkinsonism (as in Parkinson’s disease also there is a deficiency of Dopamine, thus Segawa Syndrome, which is also due to dopamine deficiency might have features of Parkinsonism), although subtle, includes:
- Slowness of Movement
- Tremors
- Stiffness
- Imbalance and inability to maintain a stable posture for long periods.
How is Segawa Syndrome diagnosed?
Segawa Syndrome is diagnosed by a Neurologist through a detailed history and clinical examination. However, the Neurologist may order certain tests, which includes:
- CSF Examination – to measure the amount of pterins (biopterins and neopterin), the levels of which are low in Segawa Syndrome
- Phenylalanine Loading Test – In Segawa Syndrome, there will be a decreased conversion of phenylalanine to tyrosine
- MRI Brain – To rule out other causes that can mimic Segawa Syndrome
- Molecular Genetic Testing – to detect GCH1 gene mutation.
Segawa Syndrome Treatment
Segawa Syndrome or Dopa-Responsive Dystonia, as the name suggests, responds dramatically to Dopa or Dopamine. Affected individuals can be treated initially with a low dose of levodopa or L-dopa, which in the body is converted to dopamine, thus replenishing the neurotransmitter that is deficient in Segawa Syndrome.
Any child presenting with dystonia or involuntary sustained muscle contractions must have this condition to be considered in the differential diagnosis. Many clinicians are of the opinion that all children with dystonia should be given a trial of levodopa, as they might be suffering from some kind of Dopa-Responsive Dystonias, which is treatable. Apart from this, genetic counseling should be sought by the affected individual and the parents for future planning.
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