Partington syndrome
Partington syndrome is a rare neurological disorder characterized by intellectual disability, focal hand dystonia, and, in some cases, epilepsy.
Overview
Partington syndrome is a neurological disorder that causes intellectual disability along with a condition called focal dystonia that particularly affects movement of the hands. Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe.
Symptoms
The intellectual disability associated with Partington syndrome usually ranges from mild to moderate. Some affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur.
Focal dystonia of the hands is a feature that distinguishes Partington syndrome from other intellectual disability syndromes. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions, tremors, and other uncontrolled movements. In Partington syndrome, this focal dystonia—often called the Partington sign—begins in early childhood and gradually worsens, causing difficulty with grasping movements or using a pen or pencil.
Other potential symptoms include:
- Dystonia affecting other parts of the body
- Impaired speech (dysarthria) due to dystonia affecting facial and speech muscles
- Awkward gait (walking)
Signs and symptoms can vary widely, even within the same family.
Causes
Partington syndrome is caused by mutations in the ARX gene. This gene provides instructions for producing a protein that regulates the activity of other genes. Within the developing brain, the ARX protein is involved with the movement (migration) and communication of nerve cells, specifically regulating genes that play a role in the migration of specialized neurons called interneurons.
The most common mutation, a duplication written as c.428_451dup, is a polyalanine repeat expansion. This expansion likely impairs ARX protein function and disrupts normal interneuron migration, leading to the intellectual disability and dystonia characteristic of the syndrome.
Inheritance
This condition is inherited in an X-linked recessive pattern. The ARX gene is located on the X chromosome. In males, one altered copy of the gene is sufficient to cause the condition. In females, a mutation would typically need to occur in both copies of the gene to cause the disorder. Fathers cannot pass X-linked traits to their sons.
Rarely, the genetic change occurs during embryonic development, leading to mosaicism, where only some cells have the genetic change. This often results in milder features of the syndrome.