Introduction
Part of the brain which controls the motor functioning of the central nervous system is the cerebellum. Incoordination of muscles can be caused due to congenital defects or lesions of the cerebellum. Various disturbed cerebellar malformations have been identified in human beings, which can lead to altered coordination of movements and legs. Certain symptoms can be observed with mutations in the VLDLR (very low-density lipoprotein receptor) gene. Association of such mutations with cerebellar hypoplasia (a condition that results in underdeveloped cerebellum) cases were reported which are described in this article.
What Is Cerebellar Hypoplasia in Humans?
Cerebellar hypoplasia is a neurological disorder that causes the cerebellum to develop smaller or underdeveloped than normal. It is a characteristic of many heredities. It is a condition characterized by cerebellar hypoplasia in a baby or young child who has reduced muscle tone, speech or delay in development, difficulty in walking and maintaining balance, seizures (uncontrolled electrical activity in the brain), intellectual incapacity, and involuntary eye movements from side to side. Symptoms in an older child may include hearing loss, clumsiness (lack of movement or action), headaches, and dizziness.
What Is VLDLR Cerebral Hyperplasia?
VLDLR-associated cerebellar hypoplasia (VLDLR-CH) is a condition that can be distinguished by symptoms such as ataxia (a condition affecting balance, coordination, and speech), which leads to ambulation (ability to walk without support), seizures, dysarthria (difficulty in speech) and intellectual disability. It is a genetically inherited condition that affects brain development. Individuals with VLDLR-CH have underdeveloped or small cerebellum (part of the brain which coordinates motor function). When this part of the brain is affected, various problems are associated with balance and ataxia (coordination), which can be seen during infancy. Development of movements or walking occurs later in childhood at the age of six. In a few cases, they would not be able to walk independently, and in a few cases, their feet and hands can lose their movement.
What Are the Causes of VLDLR-Associated Cerebellar Hypoplasia?
VLDLR-CH occurs due to VLDLR gene mutation. It is an autosomal recessively inherited disorder. This gene provides instructions for making very low-density lipoprotein (VLDL) receptor proteins. Movement of developing neurons (nerve cells) to certain locations in the brain is guided by VLDLR protein. Any changes in the functioning of the genes lead to altered production of the protein, and also, the movement of the nerve cells to reach certain parts of the brain when needed is not done. When such defects occur, brain development is hampered, leading to ataxia and other symptoms.
What Are the Clinical Features Of VLDLR-CH?
The following are the clinical features of VLDLR-CH:
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Altered walking of the individual or inability of the individual to walk independently.
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Cerebellar hypoplasia (altered coordination in the movement that occurs due to underdevelopment of the cerebellum).
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Pontine hypoplasia (a condition that occurs due to underdevelopment of the brain).
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Cerebellar ataxia (damage to the cerebellum leading to uncoordinated muscle movements leading to difficulty in walking. Most of the children can learn to walk late or can never walk independently.).
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Hypotonia (decreased muscle tone).
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Epileptic seizures (tremors or sudden involuntary jerking movements).
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Dysarthria (damage to nerves or the brain can lead to weakness of muscles that help in speech, causing difficulty in speaking).
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Strabismus (inability of the eye to line up in one direction occurs in most individuals).
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Nystagmus (abnormal or slow eye movements).
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Delayed development (delay in reaching the milestones).
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Cognitive impairment (inability to think effectively can range from mild to severe. Few can follow simple instructions and communicate with short words or sentences).
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Short stature (decrease in the height of the individual).
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Microcephaly (decrease in the head circumference).
What Is the Prevalence of VLDLR-Ch?
VLDLR-associated cerebellar hypoplasia is a rare condition, and its prevalence cannot be studied as, in most cases, the condition goes misdiagnosed or underdiagnosed.
How Is VLDLR-Associated Cerebellar Hypoplasia Diagnosed?
The following are the major diagnostic features:
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Clinical findings include ataxia, delayed ambulation, intellectual disability, and dysarthria.
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Magnetic Resonance Imaging (MRI): MRI reveals cerebellar hypoplasia along with mild hypoplasia of the corpus callosum (portion connecting the right to left cerebral hemispheres), and all the other associated brain structures were normal.
- Establishing the Diagnosis: VLDLR-CH presence can be confirmed by molecular genetic testing by identification of pathologic variants. Molecular genetic testing includes gene-targeted testing and comprehensive genomic testing combination.
- Gene Targeted Testing: This includes clinicians' involvement in determining the gene causing the condition. The individual can undergo molecular genetic testing once the clinical findings are co-related with the MRI findings.
What Are the Management Criteria for VLDLR-Associated Cerebellar Hypoplasia?
Management of the condition begins with the evaluation of the diagnosis.
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Neurologic System Evaluation: If seizures occur, it can be evaluated with brain MRI and EEG (electroencephalogram).
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Evaluation of Development: Speech assessment, adaptive and cognitive features are also assessed.
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Musculoskeletal Evaluation: Any disturbances in mobility or daily routine activities needing devices for rehabilitation and development.
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Evaluation of the Vision: Strabismus is assessed.
Mostly symptomatic treatment is carried out:
Treatment of Developmental Delay:
Developmental delay can be treated on an age basis:
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Ages 0 to 3 Years: Early intervention is necessary to target individuals' needs and treat the same.
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Ages 3 to 5 Years: Individualized education plan (IEP) can be developed to determine the treatment plan.
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All Ages: Pediatrician consultation is advised to obtain a proper treatment plan and to gain access and knowledge about the services provided by specific organizations or governments.
Treatment of Motor Dysfunction:
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Gross Motor Dysfunction: Mobility is maximized with the help of physical therapy, and ambulation can be promoted. Wheelchairs, bath chairs, and strollers are certain medical equipment that can be considered to promote movement in an individual.
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Fine Motor Dysfunction: Skills affecting functions such as grooming, writing, feeding, and dressing can be treated using occupational therapy.
Communication Issues: Alternative communication means for those individuals with language difficulties can be considered. Augmentative and alternative communication (AAC) is a tool that can range from picture exchange communication (low technology) to high-range technology which includes voice-generating devices.
Surveillance Period: Individuals with seizures and cerebellar ataxia must be evaluated after treatment at least once a year to note the episode's re-occurrence and duration.
What Is Genetic Counseling?
Providing information regarding the genetic condition mode of inheritance, the nature of the disorder, and its implications to the individual along with their family members is called genetic counseling. Family history and assessment of genetic risk are assessed, and counselling is provided through a geneticist.
Conclusion:
VLDLR-associated cerebellar hypoplasia is a genetic disorder associated with certain characteristics that need early diagnosis and treatment intervention. They present with symptoms affecting brain function that hampers an individual's daily activities. Such individuals are given symptomatic treatment and are put under surveillance. A proper diagnosis and treatment plan, along with genetic counseling, is necessary to improve the treatment outcome and prevent the occurrence of this disorder in the family.
