Introduction
Even the slightest form of error in the genetic makeup of a person can elicit disease conditions impairing and disrupting the normal functioning of the body organs. Sometimes, these errors in the genes run through families, making those with a positive family history more susceptible to these errors in their genetic makeup. The impairments inflicted by such inborn conditions vary by the types of genes involved, the severity of genetic alteration, and the extent to which the gene functions are hindered. Therefore, some inborn conditions may remain without significantly compromising the body's function, while certain others precipitate gross structural and functional impairments.
What Is Dentatorubral Pallidoluysian Atrophy?
Dentatorubral-pallidoluysian atrophy (DRPLA) is a highly infrequent inborn condition closely linked with alteration in a specific gene in the body. Naito-Oyanagi disease, myoclonic epilepsy with choreoathetosis, and Haw River syndrome are the other medical names that denote this condition. Dentatorubral-pallidoluysian atrophy was first identified in 1946, and the Japanese population elicited the highest prevalence rate.
Considering the onset age, DRPLA is categorized into two distinct groups:
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Juvenile-Onset: If manifestations are encountered within 20 years of age, they are considered to be juvenile-onset DRPLA.
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Adult-Onset: Patients whose manifestations elicited after 20 years are grouped under adult-onset.
What Led to the Development of Dentatorubral Pallidoluysian Atrophy?
Dentatorubral-pallidoluysian atrophy is identified to be the result of gene alteration, specifically with the ATN1 (atrophin-1) gene. The ATN1 gene is concerned with the formation of atrophin-1 protein, which has an integral role in the functioning of neurons. The ATN1 gene encompasses cytosine, adenine, and guanine sequences, forming a trinucleotide, repeating at specific sites within the ATN1 gene. The affected ATN1 gene elicits CAG (cytosine, adenine, and guanine) repeat expansion, particularly in the exon 5 region. The exon 5 region in the ATN1 gene is the core site that is considered to be in charge of the atrophin-1 protein synthesis. In the altered ATN1 gene, the frequency of CAG repeat tends to differ from what it should be in a normal ATN1 gene.
The extent of altered repeat length is closely related to the severity and intensity of the disease manifestations. So, the difference in the CAG repeat frequency gives rise to this rare neurological condition. The inheritance of dentatorubral-pallidoluysian atrophy is of an autosomal dominant manner, where an individual can acquire DRPLA even in the presence of a single copy of the susceptible gene. Hence, even with a single affected parent, either mother or father, there is a strong possibility (50 percent) for the next generation to acquire this inborn condition.
What Are the Symptoms Associated With Dentatorubral Pallidoluysian Atrophy?
Dentatorubral-pallidoluysian atrophy elicits various manifestations that often pose challenges and confusion in the diagnosis process. In addition, the manifestations elicited in the DRPLA condition are more or less influenced by the patient’s age, during which the condition marks its onset in the person’s body with obvious manifestations. However, certain hallmark symptoms associated with dentatorubral-pallidoluysian atrophy are common for all patients regardless of their onset age. Those hallmark findings include the following:
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Ataxia: It is marked by compromised control over various body muscles, particularly in the legs and arms. Impaired muscle control makes it difficult for the person to balance the body. It eventually gives rise to troubled walking and uncoordinated movements. The walking pattern and style will be considerably altered in patients with ataxia.
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Chorea: The muscles that make up the legs, face area, and arms elicit jerky, abrupt, unpredictable, and aimless movements. These movements are randomly and unintentionally elicited in the affected person.
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Collapsing Cognitive Skills: DRPLA brings about a collapse in cognitive skills, like memory, logical thinking, decision-making, and reasoning skills. The person experiences abrupt fluctuations in their mood and trouble in social interactions.
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Myoclonus: Besides chorea, DRPLA also gives rise to jerky and short-lived muscle spasms, known as myoclonus. These muscle twitches are uncontrollable and involuntary.
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Epilepsy: The patient experiences recurrent and continual seizure activity due to aberrant signal production in the brain. Epilepsy indicates exaggerated brain signal conduction without an external or internal triggering factor.
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Psychiatric Issues: Psychiatric issues encountered in relation to the DRPLA condition encompass unexplainable fear (anxiety), hallucination (unreal perceptions of sensations), depression (extreme sadness), and behavioral changes.
Being a progressive condition, the severity of the manifestations advances over time without therapeutic interventions. Head tremors, memory issues, and visual impairments are more frequently encountered in patients detected with adult-onset DRPLA (onset age beyond 20 years).
How Is Dentatorubral Pallidoluysian Atrophy Diagnosed?
Diagnosis of dentatorubral-pallidoluysian atrophy is often confusing because of diversified signs and symptoms. Hence, clinical manifestations need to be supported by a positive family history to guide the diagnosis of DRPLA. Genetic testing is the confirmatory diagnostic tool that aids in detecting the ATN1 gene alteration. In genetic testing, the PCR (polymerase chain reaction) technique is employed to amplify the exon 5 region, exposing the CAG repeat frequency alteration. Magnetic resonance imaging (MRI) of the brain and electroencephalogram (EEG) are other diagnostic interventions that are advised to figure out the changes in the brain structure that are suggestive of dentatorubral-pallidoluysian atrophy.
How Is Dentatorubral Pallidoluysian Atrophy Treated?
Being an inborn condition arising from altered genetic makeup, the scope for a permanent cure for the DRPLA condition is minimal and still needs to be established. Various studies are ongoing across the globe in search of a definitive treatment modality for this condition. However, certain supportive measures are advised to ease the manifestations associated with the conditions, enhancing their quality of life.
Seizures that accompany the DRPLA condition are often tackled with appropriate anti-seizure medicines. Medicines like Amantadine or Riluzole are advised for dealing with ataxia. Likewise, psychotropic drugs (psychiatric medicines) ease the patient’s psychiatric problems. Appropriate physical, rehabilitative, and occupational therapies are also employed to enhance the patient’s life quality. Therefore, dentatorubral-pallidoluysian atrophy entails the need for an integrated therapeutic approach.
Genetic counseling is another important aspect of the treatment strategy for DRPLA patients, where the patients and their parents are counseled regarding the condition. It helps the patient understand the risk of passing the condition to the succeeding generation. Preimplantation genetic testing modalities check for altered gene copies in the developing baby within the womb.
Conclusion
Dentatorubral-pallidoluysian atrophy presents various neurological manifestations. It exhibits a close likeness to certain movement disorders, which interfere with the prompt diagnosis of DRPLA. A multidisciplinary team approach encompassing specialists like neurologists, geneticists, psychologists, and occupational and physical therapists services are required to diagnose and follow up with patients diagnosed with DRPLA. Pharmacological and non-pharmacological interventions are advised to curb the manifestations and extend the patient's life expectancy.
