Introduction:
Cystic leukoencephalopathy without megalencephaly (CLEWM) is a type of rare genetic disorder that affects the white matter present in the brain. The characteristic formation sees it as fluid fill cavities or cysts in the white matter present in the brain. Most leukoencephalopathies cause enlargement in the brain, but cystic leukoencephalopathy does not cause enlargement of the brain, also called megalencephaly. So it is called cystic leukoencephalopathy without megalencephaly.
What Are the Causes of Cystic Leukoencephalopathy Without Megalencephaly?
The main cause of cystic leukoencephalopathy without megalencephaly is a genetic mutation, which affects specific types of genes involved in the maintenance and development of the white matter present in the brain. Mutation seen in the DARS2 gene is the main cause of this condition. The DARS2 gene gives instructions to produce aspartyl-tRNA synthetase, which is an enzyme that plays an important role in the synthesis of protein within the cell. This enzyme helps in attaching the amino acid aspartic acid to the transfer RNA (ribonucleic acid), which helps in the accurate assembly of proton proteins. The mutation seen in the DARS2 gene will disrupt the normal functioning of the enzyme aspartyl RNA resulting in abnormalities during protein synthesis. The specific reason affecting the white matter present in the brain is not fully understood, but the mutation of the DARS2 gene can cause impaired myelination.
What Are the Clinical Features of Cystic Leukoencephalopathy Without Megalencephaly?
The commonly seen clinical features and symptoms of cystic leukoencephalopathy without megalencephaly include the following:
-
Developmental Delays - Children with this condition can have developmental delays in reaching the milestone. Walking, sitting, crawling, and speech development will be delayed in children with CLEWM. It is noticeable during the early childhood period of infancy.
-
Intellectual Disability - People with CLEWM can develop an intellectual disability that can be mild to severe. It will affect different cognitive functions like problem-solving, memory, learning, and overall intellectual abilities.
-
Impaired Motor Function - A reduced motor function is commonly seen in CLEWM. It includes poor coordination, difficulty in stability, balance, and gait, muscular weakness, and reduced fine motor skills.
-
Seizures - Different types of seizures can be seen in CLEWM. It can be seen as a focal seizure that is limited to a specific part of the brain, or it can appear as a generalized seizure that will affect the entire part of the brain.
-
Vision and Hearing Impairments - Some people with CLEWM can have visual impairments like optic atrophy or optical nerve damage, visual field defect, and reduced acuity. Hearing impairments are also seen with this condition, like sensorineural hearing loss.
-
Behavioral and Psychiatric Issues - Behavior changes like impulsivity, hyperactivity, and attention defects, and psychiatric symptoms like stress, anxiety, or mood disorders can be seen in individuals with CLEWM.
-
Speech and Language Difficulties - Communication difficulties are commonly seen in CLEWM. Speech articulation problems, delayed speech development, and challenges faced during expressing and receptive language skills are seen in this condition.
-
Progressive Neurological Decline - It is a progressive disorder, and the symptoms will worsen over time. There will be a deterioration in the motor skill of the patient. Cognitive abilities and most neurological functions will decline over time.
What Are the Diagnostic Tests Used in Cystic Leukoencephalopathy Without Megalencephaly?
Some of the diagnostic processes used to detect cystic leukoencephalopathy without megalencephaly include the following:
-
Clinical Evaluation - A detailed medical history and a comprehensive physical examination will be done. The neurological examination also helps in diagnosing this condition. Symptoms associated with this condition, like motor impairment, seizures, intellectual disabilities, developmental delays, and visual or hearing abnormalities, will be noted.
-
Neuroimaging Studies - Imaging techniques like magnetic resonance imaging (MRI) of the brain help in evaluating the white matter and will identify any cysts or abnormalities present in the brain.
-
Genetic Testing - Genetic testing is very important in diagnosing CLEWM. It helps in analyzing the DNA (deoxyribonucleic acid) of the patient and will identify the genetic mutation. It focuses on testing the DARS2 gene, which causes CLEWM.
How Is Cystic Leukoencephalopathy Without Megalencephaly Managed and Treated?
Cystic leukoencephalopathy without megalencephaly can be treated by the following methods:
-
Symptomatic Care - The symptoms and complications associated with this condition are treated initially. This includes the usage of anti-epileptic medication to reduce seizures, occupational and physical therapy to help in improving mobility and motor function, and to address communication difficulties; speech and language therapy are used.
-
Supportive Care - Supportive care is given to the patients to manage their day-to-day activities and to improve their overall well-being. Mobility aids and assistive devices are used to help with movement and independence. Adaptive technology is used to improve communication abilities.
-
Regular Monitoring and Follow-up - Regular monitoring of the health and neurological function of the patient is important in detecting the progression of the treatment, and it also helps in identifying the complications. Regular follow-up with the healthcare professional is needed to ensure the proper management and timely intervention of the disease.
-
Educational Support - Educational support, like individualized educational plans, helps to accommodate and modify the environment and also helps in improving cognitive development.
What Is the Differential Diagnosis of Cystic Leukoencephalopathy Without Megalencephaly?
Some of the differential diagnoses of cystic leukoencephalopathy without megalencephaly include the following:
-
Megalencephalic leukoencephalopathy with a subcortical cyst.
-
Other leukoencephalopathies.
-
Lysosomal storage disorders.
-
Other genetic disorders.
-
Acquired causes like metabolic disorders or post-infectious encephalitis.
What Is the Prognosis of Cystic Leukoencephalopathy Without Megalencephaly?
The prognosis of cystic leukoencephalopathy without megalencephaly can vary depending on the disease's severity and progression rate. The severity of the neurological impairment, like motor impairment, developmental delays, sensory deficit, intellectual disabilities, etc., can determine the prognosis. The cognitive function and motor function are also considered during the prognosis. The prognosis of this condition is good when the severity of the disease is mild.
Conclusion:
In conclusion, cystic leukoencephalopathy without megalencephaly is a genetic disorder that is rare and is characterized by the formation of cysts in the brain. It is usually seen in the white matter of the brain. It does not cause enlargement in the brain. Autosomal recessive traits inherit it. It is usually present in infancy or the early childhood period, and this is with development and hearing impairments. Diagnosis is made by neuroimaging studies and different genetic testing. A multi-disciplinary approach is needed in the management of CLEWM.
