The Collaborative Center for X-linked Dystonia Parkinsonism (XDP) at Massachusetts General Hospital provides resources and treatment information to patients with XDP.
What is X-linked Dystonia Parkinsonism?
XDP is an adult-onset, genetic movement disorder which affects individuals who descend from the Philippine Island of Panay. It is a neurodegenerative disease that evolves over the course of many years, resulting in significant disability and a shortened life span.
Phases of XDP
XDP generally presents in three different clinical phases.
People with dystonia have involuntary, sustained muscle contractions. These involuntary muscle contractions can cause twisting, repetitive movements and abnormal postures. The twisting seen in XDP patients happens because the brain sends signals that tell muscles to tighten and contract involuntarily.
In XDP, dystonia can occur in any part of the body and may spread to other body parts during disease. It can manifest in many ways, including twisting/dragging a foot, repeated jaw opening and closing, abnormal turning or posture of the neck, tongue protrusion, mouth pursing or excessive eye blinking. Many patients begin showing symptoms in their forties, but the age of onset can vary greatly.
When one part of the body is affected, it is called focal dystonia.
Over time, more muscles become affected, leading to twisting and uncomfortable postures with muscle spasms. After five years, most patients have developed a generalized dystonia, where many different muscle groups and body parts are affected.
Dystonia and Parkinsonism
The next phase of XDP usually begins 7-15 years after onset of focal dystonia. During this phase, the patient has features of both generalized dystonia as well as parkinsonism.
Parkinsonism involves the development of symptoms that are classically associated with Parkinson's disease, but can also be seen in many other conditions. These involve slowing of movements, shuffling gait, development of a hand tremor and reduction of facial expression. Patients with XDP do not have Parkinson's disease, which is not a genetic condition and is caused by a different mechanism.
By 15 years after onset, XDP patients primarily show features of parkinsonism. In 6% of patients, XDP manifests primarily as parkinsonism, without evidence of dystonia.
As XDP progresses, patients become more disabled and are eventually unable to work. In the late stages of disease, patients become dependent on others, immobile and unable to care for themselves. Patients with XDP have a reduced life expectancy due to the complications of the disease.
Not all patients present with the same symptoms or progress at the same rate. CCXDP clinical researchers are currently conducting natural history studies in the Philippines and North America to define the full spectrum of disease to understand this variation. These studies are crucial for eventual clinical trials and may provide insights that allow earlier interventions to improve patient outcomes.
What causes XDP?
XDP is caused by a genetic mutation that can be passed down from parent to child. Recent CCXDP-funded research studies have shown that XDP is most likely caused by a DNA insertion (retrotransposon) in a gene called TAF1. The DNA insertion contains a repetitive sequence, the length of which can vary among patients. The longer repeat sequences can lead to an earlier age of disease onset. One consequence of the insertion is a decrease in TAF1 gene expression. Studies are underway to normalize TAF1 expression in hopes of providing clinical benefit to patients.
Where is Panay Island?
Panay is one island in the Philippines, which is in southeast Asia. The Philippines has a population of roughly 100 million and is made up of over 7,000 islands. Panay is part of a group of islands called the Visayas in the central part of the Philippines. Panay is divided into five provinces; Aklan, Antique, Capiz, Iloilo and Guimaras (a small island off Panay).
There are more than 12 million people of Filipino descent who live overseas in many countries around the world, including the United States.
I am Filipino, why have I not heard of XDP?
The highest concentration of XDP patients is on the island of Panay in the Philippines. XDP patients in the United States or elsewhere can usually trace their maternal ancestry to Panay. How then could someone with family on or from Panay not know about the disease?
Unfortunately, for many years families did not understand what XDP was. The drastic twisting and jaw opening that many patients exhibited caused families to be ashamed. As a result, patients were often confined to their homes or hidden from the community due to the significant social stigma associated with disease. This may help explain the lack of widespread knowledge about XDP.
Through education and outreach, the Collaborative Center for XDP hopes to further understanding of the disease and provide support for XDP patients and their families.
Is Genetic Testing Available?
Yes. Please contact our genetic counselor, Trisha Multhaupt-Buell, at XDP@partners.org for additional information.
What are Treatment Options for Patients?
The Center recognizes the devastating toll that XDP takes on patients and their families.
Patients usually start exhibiting symptoms in their early forties after they have had children. At this time in their lives, they are likely an important source of income for their family. Without this income, families often descend into poverty.
The Center is dedicated to helping such families by providing better access to medicines, clinical care and emotional support. We have employed a network of community advocates on Panay island to help us understand the daily struggles patients face and the barriers that often prevent access to medical care. Learn more about our humanitarian mission and our partner, The Sunshine Care Foundation.
How Can I Help?
The Center supports ongoing efforts at Mass General Brigham and in the Philippines to collect, process, and store samples and clinical information from XDP patients and their family members.
These samples are a crucial resource for scientists all over the world to increase our understanding and treatment options for this debilitating disease. For more information please contact Trisha Multhaupt-Buell at DystoniaResearch@partners.org.
- American Dystonia Society
- Mass General Movement Disorders Clinic
- Dystonia Medical Research Foundation
- National Institutes of Health (NIH) Dystonias Fact Sheet
- Tyler's Hope for a Dystonia Cure
- Dystonia Coalition (Rare Diseases Clinical Network)
- Movement Disorders Society of the Philippines
- X-Linked Dystonia-Parkinsonism Recent Advances
- Imaging gradual Neurodegeneration in basal ganglia model disease
- Long-term outcomes of bilateral pallidal deep brain stimulation for X-Linked Dystonia-Parkinsonism
- The natural history of sex-linked recessive dystonia parkinsonism of Panay, Philippines (XDP)