Partington syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 4, 2017
StartDiseasesPartington syndrome

Partington syndrome is the result of a rare neurological disorder. The condition is characterized by intellectual disability and involuntary movement problems that primarily affect the hands. The number of people living with Partington syndrome is not clear; however, the condition does affect males more often than females.

Contents

Definition & Facts

Partington syndrome has an X-linked recessive inheritance pattern. This means that the gene associated with the disorder is found on the X chromosome. The X chromosome is one of the two sex chromosomes. Males have one X chromosome and one Y chromosome. A mutation on the single X chromosome in a male is sufficient to cause Partington syndrome. Since females have two copies of the X chromosome, they would have to inherit the defective gene in both chromosomes in order to have the condition. This is why the disorder is more common in males. Females with a mutation on one X chromosome are genetic carriers and may have some symptoms; however, they are usually less severe than those seen in males.

Symptoms & Complaints

The level of intellectual impairment and severity of other symptoms associated with Partington syndrome can vary significantly from person to person, even among members of the same family.

In addition to mild to moderate intellectual disability, individuals with the condition may have behavioral problems and difficulties with communication and social interactions similar to autism spectrum disorders.

A movement disorder, known as focal dystonia, typically begins during childhood and gets progressively worse. The dystonia normally affects grasping movements, such as holding a pen or pencil. The fact that the dystonia primarily affects the hands is a characteristic that distinguishes Partington syndrome from other intellectual and neurological conditions.

Occasionally, the dystonia will affect muscles in other parts of the body, which can cause problems with speech and walking. Epilepsy characterized by recurrent seizures may also occur in patients with Partington syndrome.

Causes

Partington syndrome is the result of a mutation involving the ARX gene located on the X chromosome. The ARX gene carries the instructions for producing a particular protein responsible for regulating the activity of other genes. During brain development, the protein is involved in regulating the movement of specialized neurons to their proper location as well as communication between neurons. The ARX protein is also involved in regulating how cells differentiate and mature into various body structures, including the brain, testes, pancreas, and skeletal muscles used for movement.

Under normal circumstances, the protein produced by the ARX gene contains four sections of an amino acid called alanine. In patients with Partington syndrome, one of these sections contains extra alanines. This expansion of the alanine section interferes with the normal protein function and may prevent cell differentiation and keep neurons from migrating to their proper location during brain development. This leads to the dystonia and intellectual impairment characteristic of Partington syndrome.

Diagnosis & Tests

As with any rare disease, diagnosing Partington syndrome can be challenging. Since the condition is X-linked, a detailed family history will likely reveal a pattern of male family members with similar symptoms.

In many cases, the patient will also have a history of seizures. The parent of a child with Partington syndrome will often express concern that the child is not meeting developmental milestones, which is an indication of intellectual disability. This may include

  • A failure to develop language and motor skills,
  • Difficulty adjusting to new situations,
  • An inability to keep up in school
  • An inability to understand or follow social rules.

The level of intellectual impairment can be assessed using a variety of developmental exams. A physical examination will reveal tremors, muscle contractions, and involuntary movements affecting the hands that make it difficult for the patient to perform manual tasks requiring a grasping motion.

In some instances, laboratory and imaging tests may be used to rule out other potential causes of seizures and intellectual and neurological impairment. Genetic testing is available to identify the mutation of the ARX gene that is responsible for Partington syndrome. 

Treatment & Therapy

There is no cure for Partington syndrome. The treatment of the condition depends on the specific presentation of symptoms in each person. The involuntary muscle movements, spasms, and contractures caused by the dystonia may improve with medications as well as physical therapy and occupational therapy. Individuals with the condition may require walkers or other mobility aids to cope with gait abnormalities.

Children with speech difficulties caused by Partington syndrome may benefit from speech therapy. Those with the condition may also require anticonvulsant medications to control recurrent seizures. Depending on the level of intellectual disability, individuals with the condition may require special education classes and assistance with activities of daily living.

Specialized behavioral therapy may help with social and communication skills and allow the individual to lead as normal a life as possible. These therapies are most effective when started as early as possible. Most patients with the condition benefit from a multi-disciplinary treatment approach, including their primary care doctor, neurologists, speech therapists, physical therapists, occupational therapists, educators, and counselors.

Prevention & Prophylaxis

Since Partington syndrome is inherited, there is no way that it can be prevented. A woman who has the Partington mutation on her X chromosome is considered a carrier. All of her sons will inherit the mutation and have the condition. All of her daughters will also inherit the mutation and will be considered carriers as well.

Men with the Partington mutation will pass the mutation to their daughters but not their sons. The only way for a female to have Partington syndrome is if both parents have the genetic mutation.

Individuals with a family history of Partington syndrome may wish to undergo genetic testing and genetic counseling in order to better understand the possibility of passing the condition to their offspring. Living with or caring for someone with a genetic condition can be challenging. Individuals with Partington syndrome and their family members should talk to their health care providers about available support groups for those coping with the condition.