Cerebral palsy of genetic origin as an expanding field within neurology and genetics

Cerebral palsy is a group of neurological disorders of psychomotor development that can appear in childhood and permanently and irreversibly affect body movement and muscle coordination, thus generating permanent disabilities. They may also be accompanied by sensory, cognitive, communication and perception problems and sometimes may include behavioral disorders.

Its origin is broad, but basically they are areas of the brain that participate in muscular movement which develop abnormally during fetal growth, or may be the result of an injury to the brain either before, during or after birth up to 3 years of age.

Cerebral palsy has an incidence of 2-3 per 1,000 live births in developed countries, which has decreased in recent decades thanks to advances in medical care. Cerebral palsy is the leading cause of childhood disabilities in the United States, but it does not always cause profound disabilities. Someone with mild cerebral palsy may not need help or may have mild problems, such as difficulty walking, while a person with severe cerebral palsy may need special equipment or lifelong care. The disorder is nonprogressive, meaning it does not get worse over time, and some symptoms may even change as the child grows.

There is no cure for cerebral palsy, but supportive care and medical intervention are a great help to the patient, and medications and surgery can help many people improve their motor skills and their ability to communicate with the world. 

Classification of Cerebral Palsy

1. Spastic Cerebral Palsy: Characterized by rigid and tense muscles.
2. Ataxic Cerebral Palsy: It involves coordination and balance problems.
3. Dyskinetic Cerebral Palsy: Involuntary movements and fluctuations in muscle tone occur.

Cerebral Palsy can present in varying degrees of severity, from mild to severe, and is often accompanied by related disabilities such as:

• Intellectual disability: Approximately 30-50% of people with cerebral palsy have intellectual disabilities.
• Seizure disorder: Up to half of all children with cerebral palsy have one or more seizures. Children with cerebral palsy and epilepsy are more likely to have intellectual disability.
• Growth retardation and psychomotor development: Children with moderate to severe cerebral palsy often have delays in growth and development. 
• Hypotrophy: Muscles and limbs affected by cerebral palsy tend to be smaller than normal.
• Spinal deformities, osteoarthritis, osteoporosis: Spinal deformities, including scoliosis (curvature), kyphosis (hunchback), and lordosis (arched back), are associated with cerebral palsy. Pressure and misalignment of the joints can lead to pain and breakdown of cartilage in the joints, as well as enlargement of the bones.
• Vision problems: Strabismus. Some children with cerebral palsy have difficulty understanding and organizing visual information. Other children may have vision problems or blindness in one or both eyes.
• Hearing loss or decrease: partial or complete hearing loss, particularly as a result of jaundice or lack of oxygen to the developing brain.
• Speech and language disorders: Speech and language disorders, such as difficulty forming words and speaking clearly, are present in more than one-third of people with cerebral palsy.
• Sialorrhea or hypersalivation: Lack or decreased control of the muscles of the throat, mouth and tongue can lead to excessive salivation.
• Incontinence: A possible complication of cerebral palsy is incontinence, caused by poor control of the bladder muscles.
• Abnormal sensations and perceptions: Some people with cerebral palsy experience pain or have difficulty feeling simple sensations, such as touch.
• Learning difficulties: Cognitive impairment in children with cerebral palsy can arise when processing certain types of spatial and auditory information.
• Long-term infections and illnesses: Many adults with cerebral palsy are at increased risk for heart and lung disease and recurrent pneumonia. Recurrent pneumonia and lung disease are a feature of the condition of the paralysis as is the functional limitation, pulmonary physiotherapy helps to reduce recurrences.
• Contractures: Muscles can become painfully fixed in abnormal positions, called contractures, which can increase muscle spasticity and joint deformities in people with cerebral palsy.
• Malnutrition: Difficulties with swallowing, sucking or feeding can cause many people with cerebral palsy, especially infants, to fail to get adequate nutrition and to fail to gain or maintain weight.
• Dental problems: This is a factor more associated with care, due to poor oral hygiene, either due to lack of care or difficulty opening the mouth.
• Inactivity: Many children with cerebral palsy cannot participate in sports and other activities at a sufficient level of intensity to develop and maintain strength and fitness.
• bone health: Bone density is considerably lower in people with cerebral palsy and puts them at risk for bone fractures.
• Psychological effects: People with cerebral palsy are at greater risk of anxiety, depression, and social and emotional problems than the general population due to the disabling nature of their condition.

Genetic origins of cerebral palsy

Research into genetic PC has revealed that multiple genes may be involved in its development. These alterations may include:

• Point mutations: Changes in a single base in DNA that can affect the function of certain proteins in the brain.
• Deletions or duplications: Loss or addition of DNA segments that can cause genetic dysregulation.
• Trichotions: Alterations that affect the structure of DNA and can cause problems in the synthesis of essential proteins.

Associated Genetic Conditions

There are several genetic conditions that have been associated with cerebral palsy, including:

• Mutations in the GABRB3 gene: This gene is related to the function of neurotransmitters in the nervous system and its alteration can affect motor development.
• Angelman syndrome: Disorder caused by the deletion of a specific gene on chromosome 15, which may manifest with abnormal motor movements.
• Marshmallow-Related Cerebral Palsy (MRCP)): A recent term that includes rare syndromes with PC manifestations as part of the spectrum.
• 1p36 deletion syndromes: Associated with dysmorphology and motor disorders, including CP.

Biological Mechanisms

The biological mechanisms underlying genetic cerebral palsy are complex. Dysfunction in the pathways that regulate neuronal growth, neuronal migration and myelination (formation of the myelin sheath around neurons) may contribute to the development of CP. In addition, the interaction between multiple genes and environmental factors may influence the final phenotype of the patient.

Neurodevelopment and Plasticity

The developing brain is highly plastic, meaning it has the ability to reorganize itself in response to experiences. Genetic alterations that affect neuroplasticity can result in abnormal movement patterns. Recent research suggests that identifying genetic biomarkers could help predict CP risk in neonates.

Diagnosis

Diagnosis of cerebral palsy of genetic origin involves a combination of clinical and genetic methods:

1. Neurological Evaluation

Doctors perform a thorough examination to assess the patient's muscle tone, reflexes, and motor skills. Motor development milestones are compared to age-appropriate growth norms.

2. Symptoms of cerebral palsy

Everyone with cerebral palsy has problems with movement and posture. The type and severity of cerebral palsy symptoms differ from person to person and may even change over time. Symptoms can vary greatly from person to person, depending on which parts of the brain have been injured.

Children with cerebral palsy have a wide variety of symptoms, including:

• Lack of muscle coordination when performing voluntary movements. (ataxia)
• Stiff or tense muscles and exaggerated reflexes. (spasticity)
• Weakness in one or both arms or legs.
• Walking on tiptoe, walking crouched down, or having a “scissor” gait
• Variations in muscle tone, either too stiff or too flaccid.
• Shaking (trembling) or random, involuntary movements.
• Delays in reaching motor skills milestones.
• Difficulty with precise movements, such as writing or buttoning a shirt.

Warning signs

During psychomotor development:

Children under 6 months of age:

• The baby's head hangs down when he is lifted while lying on his back.
• They feel stiff.
• They feel flaccid.
• When they are lifted, their legs become stiff and crossed as if in scissors.

Older than 6 months of age:

• They don't turn around in any direction.
• They can't put their hands together.
• They have difficulty bringing their hands to their mouth.
• They extend one hand while holding the other in a fist.

Older than 10 months of age:

• They crawl in a crooked manner, pushing themselves with one hand and leg while dragging the opposite hand and leg.
• They cannot stand even by holding on to a support.

3. Imaging Studies

Magnetic resonance imaging (MRI) or computed tomography (CT) can be used to identify structural abnormalities in the brain. This can help rule out other neurological disorders.

4. Genetic Testing

Genetic testing is becoming a standard tool in diagnosing PC. These tests can identify mutations or chromosomal alterations that indicate a genetic origin. Specific gene panels have been developed to identify genetic conditions commonly associated with PC.

Treatment and Management

• Multidisciplinary Interventions

Treatment for genetic cerebral palsy is multidisciplinary and involves a team of specialists, which may include pediatricians, neurologists, physical therapists, occupational therapists and speech therapists.

• Physical and Occupational Therapy

Physical therapy focuses on improving motor control and mobility, while occupational therapy helps patients develop skills to perform everyday activities. Speech therapy is also essential to address communication issues.

• Medication

Medications can be used to manage symptoms such as spasticity, seizures, and pain. Drugs such as baclofen, diazepam, and antiepileptics are common.

• Surgical Interventions

In certain cases, surgical intervention may be necessary, such as orthopedic surgery to correct deformities or selective dorsal root surgery to treat severe spasticity.

• Psychosocial Support

Emotional support is critical. Families often face significant challenges and access to support groups and community resources can be invaluable.

• Family and Social Impact

Cerebral palsy due to genetic causes affects not only the individual, but also their family members and caregivers. Families must adjust to the reality of caring for a child with special needs, which can cause emotional, financial and practical stress. Providing support resources, education and networks to families to help them cope with these challenges is essential.

• Family Stress

Stress can result from constant caregiving, the cost of medical care, and uncertainty about the child's future. Counseling and family therapy can be helpful in improving caregivers' mental health.

• School Inclusion

Inclusion in regular educational settings can be challenging. It is critical to work collaboratively with schools to ensure that children receive the attention and accommodations necessary to succeed.

• Research and Future Advances

Research into genetic cerebral palsy is constantly evolving. Advances in genetics and molecular biology are leading to a better understanding of the inner workings of the brain and how genetic alterations contribute to CP.

Genetic Studies

The identification of new genes and mutations associated with PC may open the door to more personalized therapeutic approaches. Research into the use of gene therapy to correct or mitigate the effects of specific mutations shows promising potential.

Innovative Therapies

Innovative therapies, including stem cell-based therapies and gene therapy, are in various stages of research and could offer new opportunities for the treatment of cerebral palsy.

Cerebral palsy of genetic origin is an expanding field within neurology and genetics. As progress is made in understanding the genetic mechanisms underlying CP, it is crucial that the medical and scientific community collaborate to improve diagnosis, treatment and support for affected families. Social and educational inclusion, along with access to adequate health resources, are essential to improve the quality of life of these patients. In the future, the focus on personalized treatment and continued research promise a more hopeful horizon for those affected by this complex condition.

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We also have other articles related to the topic of genetics, which you can access through: https://eneviahealth.com/blog/ Here are some of them:

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