Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, progressive neurological disorder that may cause involuntary movements, cognitive difficulties, emotional and mental health issues, and seizures.

DRPLA occurs when a specific gene variant leads to structural changes in a brain protein. These changes can disrupt normal cell functions, resulting in symptoms such as cognitive decline and uncontrolled movements.

The global prevalence of DRPLA remains uncertain, but scientists consider it very rare. It is most common in the Japanese population, where scientists estimate it affects 2 to 7 per million people.

There is no cure for DRPLA, but treatment can help manage the symptoms and improve a person’s quality of life.

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The signs and symptoms of DRPLA vary according to a person’s age at the onset of the disease.

When DRPLA occurs in people before age 20, doctors call it juvenile onset. Symptoms typically include:

  • myoclonus, sudden, uncontrolled muscle jerks
  • ataxia, a lack of muscle control and coordination
  • seizures
  • progressive intellectual decline
  • behavioral changes

Doctors call DRPLA beginning after age 20 adult onset. The symptoms include:

  • ataxia
  • dementia, a group of symptoms of cognitive decline, such as memory and communication problems
  • choreoathetosis, a combination of two types of involuntary movements called chorea and athetosis
  • psychiatric symptoms such as delusions
  • visual problems and head tremors

A person can inherit DRPLA in an autosomal dominant manner, which means a single copy of a gene variant in each cell, passed down from one parent, is enough to cause the condition.

A variant in the ATN1 gene causes DRPLA.

The ATN1 gene is involved in producing a type of protein called atrophin 1, which scientists believe may be important for the brain’s nerve cell function. The medical term for nerve cells is neurons.

The gene variant that causes DRPLA affects a segment of DNA known as CAG trinucleotide repeat. The segment is made up of three repeating DNA nucleotides, or building blocks, called cytosine, adenine, and guanine.

The CAG DNA segment usually repeats 6 to 35 times within the ATN1 gene. In people with DRPLA, it repeats 35 to 93 times. The excessive repeats change the structure of the atrophin 1 protein, which builds up in the neurons and disrupts their functioning. The cells malfunction and eventually die, which leads to the symptoms of DRPLA.

Children affected by DRPLA may develop symptoms earlier than their affected parent due to larger repeat CAG sizes with every generation. Onset may be 26 to 29 years earlier than affected fathers and 14 to 15 years earlier than affected mothers.

Because DRPLA is rare and the symptoms and age of onset vary widely, the condition is challenging to diagnose. There is currently no general consensus among doctors on the diagnostic criteria. However, various tests and other findings can help them establish a diagnosis. These include:

  • Symptoms: A doctor may test for symptoms, such as movement and coordination problems, seizures, and mental and emotional difficulties.
  • Family history: A doctor may take a family history of the condition and Japanese familial origin into account.
  • Brain MRI: A brain MRI scan may provide indications of DRPLA, such as white matter lesions and degeneration of the cerebellum, the area of the brain that helps with movement and coordination.
  • Genetic testing: Genetic tests may detect abnormally long CAG repeat segments within the ATN1 gene. However, they may not be able to determine the precise number of repeats.

There is no cure for DRPLA, but supportive treatment can help a person manage the symptoms. Treatment may involve:

  • Medication: These include antiseizure drugs like perampanel (Fycompa) and levetiracetam (Keppra) to treat seizures, and risperidone and tetrabenazine (Xenazine) to treat choreoathetosis and other symptoms.
  • Psychiatric and neurological assessments: These can help healthcare professionals evaluate and treat cognitive difficulties and mood disorders.
  • Physical and occupational therapy: Physical and occupational therapy may help a person develop management strategies for movement difficulties.
  • Speech and language therapy: A therapist may help a person manage communication problems linked to cognitive and muscle symptoms.

Possible complications of DRPLA include:

  • Status epilepticus: Status epilepticus occurs when a seizure lasts for five minutes or more, or when a person has successive seizures without regaining consciousness in between them. The condition is a medical emergency that can cause brain damage and may be life threatening.
  • Progressive repetitive seizures: Seizures that become more severe over time.
  • Dysphagia: Dysphagia refers to difficulty swallowing.
  • Aspiration pneumonia: Dysphagia may lead to aspiration pneumonia, which occurs when a person breathes a substance into their lungs instead of swallowing it.

People with DRPLA face progressively challenging physical, mental, and emotional symptoms. Witnessing a family member experience these challenges can be overwhelming and may cause feelings of grief and helplessness.

Some people may be caregivers to family members with DRPLA, which can involve helping them with daily living, organizing medication and medical appointments, and providing emotional support. Caring for a family member can also lead to stress and overwhelm, especially as the symptoms worsen over time.

Resources are available to help and support family members of those with DRPLA. A person may seek support from:

  • social workers
  • in-home caregivers, such as a person qualified in medical care, or someone to help with housekeeping
  • respite or palliative caregivers or facilities
  • local and community resources
  • online and in-person support groups

Find support

The following organizations may offer information, support, and other resources:

  • CureDRPLA: This non-profit organization provides information and access to support groups for people with DRPLA and their family members.
  • The National Ataxia Foundation (NAF): The NAF offers an online tool to find a local support group, access to online support groups, information, and other resources.
  • Parent to Parent USA: This organization provides an online tool for parents of children with special needs to find local support. It also offers information and other resources.
  • Global Genes: The organization offers personalized services for people with rare diseases and their caregivers, resources dedicated to mental health and well-being, and access to a community for information and support.
  • The Family Caregiver Alliance (FCA): The FCA provides information, support, and resources for family caregivers.
  • The National Alliance for Caregiving (NAC): The NAC hosts the Caregiver Nation Network, which shares knowledge and provides a community platform for caregivers.

Genetic Counseling

Family members of those with DRPLA may want to consider genetic testing and counseling. A person with DRPLA has a 50% chance of passing it to their children.

Genetic testing involves analyzing a person’s DNA to identify specific gene variations. Genetic counseling can help people understand their genetic risks and make informed medical and personal decisions.

A healthcare professional may refer an individual to a specialist for genetic testing and counseling.

Current research into DRPLA shows promise for potentially curative treatments. The research focuses on preventing the expression of the variant ATN1 gene that leads to DRPLA.

Scientists have had some success with transcription silencing in animal models. This involves targeting the way a gene’s DNA sequence is copied to RNA, a nucleic acid that carries instructions from DNA for producing proteins.

The process of decoding the instructions in messenger RNA (mRNA) and using the information to build proteins is called translation. Another avenue of promising research involves using targeted RNA small molecules that affect the translation of the variant ATN1 gene responsible for DRPLA.

There is no cure for DRPLA, and the life expectancy for the disease is 8 to 16 years from the onset of symptoms. The disease may cause more severe symptoms and a shorter life expectancy if the CAG DNA segment repeats more than 48 times.

Early diagnosis and treatment may improve a person’s symptoms and quality of life.

DRPLA is a rare, progressive neurodegenerative disease. A variant in the ATN1 gene causes the condition, which a person may inherit from a parent.

The disease can cause different symptoms in different age groups, but symptoms typically involve uncontrolled muscle movements and cognitive decline.

There is no cure for DRPLA. However, treatments can help a person manage the symptoms and improve their quality of life. Support and resources are available to help people with the disease and their families.