X-linked dystonia parkinsonism

A rare genetic disorder affecting movement

X-linked dystonia parkinsonism (XDP), also known as Lubag syndrome, is a rare genetic disorder characterized by a combination of dystonia and parkinsonism. It is primarily found in individuals of Filipino descent, particularly those from the island of Panay in the Philippines.

Clinical Features

X-linked dystonia parkinsonism presents with a range of neurological symptoms. The disorder typically manifests in adult males, with onset usually occurring in the third to fifth decades of life. The clinical features include:

• Dystonia: Involuntary muscle contractions that cause repetitive movements or abnormal postures. In XDP, dystonia often affects the face, neck, and limbs.
• Parkinsonism: Symptoms similar to Parkinson's disease, including bradykinesia (slowness of movement), rigidity, and tremor.
• Progression: The disorder is progressive, with dystonia often preceding parkinsonism. Over time, the symptoms can lead to significant disability.

Genetics

X-linked dystonia parkinsonism is inherited in an X-linked recessive pattern. This means the gene responsible for the disorder is located on the X chromosome. Males, having only one X chromosome, are more frequently and severely affected. Females, with two X chromosomes, are typically carriers and usually do not exhibit symptoms.

The genetic mutation associated with XDP has been identified in the TAF1 gene, which plays a role in transcription regulation. The specific mutation involves a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene.

Diagnosis

Diagnosis of X-linked dystonia parkinsonism is based on clinical evaluation, family history, and genetic testing. The presence of characteristic symptoms in a male patient of Filipino descent, particularly from Panay, may prompt genetic testing for the TAF1 mutation.

Management

There is currently no cure for X-linked dystonia parkinsonism. Treatment focuses on managing symptoms and improving quality of life. Options include:

• Medications: Levodopa and other dopaminergic agents may be used to manage parkinsonian symptoms. Anticholinergics and muscle relaxants can help alleviate dystonia.
• Botulinum toxin injections: These can be effective in reducing focal dystonia.
• Deep brain stimulation (DBS): A surgical option for severe cases, DBS can help control both dystonia and parkinsonism by modulating brain activity.
• Physical therapy: Helps maintain mobility and function.

Epidemiology

X-linked dystonia parkinsonism is rare, with most cases reported in the Philippines. The prevalence is highest in the Capiz province on the island of Panay, where it is estimated to affect approximately 1 in 4,000 males.

Research

Ongoing research aims to better understand the genetic and molecular mechanisms underlying XDP, with the hope of developing targeted therapies. Studies are also exploring the role of environmental factors in the expression and progression of the disorder.

Related pages

• Dystonia
• Parkinsonism
• Genetic disorders
• Movement disorders