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Neurogenetics

neurogenetics  In Nagpur, is a cutting-edge field unraveling the genetic underpinnings of brain structure, function, and development. Researchers employ advanced analytical and molecular tools to delve into the complex genetic mechanisms shaping the brain.

In  research has transitioned from single-gene effects to studying the interplay among multiple genes affecting complex traits heritability.Since, Using modern bioinformatic and molecular methods like association studies and microarrays, researchers are uncovering valuable insights into the regulation .

Neurologic disorders

Neurogenetic disorders rank as the second most common reason for the referral to a Neurosys Multispecialty center. Thus, reflecting the extensive involvement of the approximately half of our 20,000 genes in the nervous system. The first neurogenetic disease gene was discovered in the early years of this millennium, HTT elucidating Huntington’s disease. Once, This breakthrough led to the uncovering the genetic roots of a over a hundred neurogenetic disorders.

Key take-home messages: the necessity of careful phenotyping and close collaboration with many varied experts. Careful history of family and detailed genetic counseling as a result of high proportion of negative results. Thus, the field continues to progress with improving technology, and new advances highlight the need in the future for interdisciplinary collaboration between neurologists, geneticists, and counselors to ensure the best possible care for patients with neurogenetic disorders.

Key Concepts in Neurogenetics:

  • Genetic Mutations:
    • Monogenic Disorders: These are caused by mutations in a single gene, such as Huntington’s disease or Duchenne muscular dystrophy.
    • Polygenic Disorders: These arise from the interaction of multiple genes, often combined with environmental factors, as seen in conditions like schizophrenia and autism spectrum disorders (ASD).
    • De Novo Mutations: These mutations occur spontaneously and are not inherited from either parent, often seen in disorders like Rett syndrome.
  • Inheritance Patterns:
    • Autosomal Dominant: A mutation in one copy of the gene is sufficient to cause the disorder (e.g., Huntington’s disease).
    • Autosomal Recessive: Two copies of the mutated gene (one from each parent) are required to cause the disorder (e.g., spinal muscular atrophy).
    • X-linked: Mutations on the X chromosome, which can predominantly affect males (e.g., Duchenne muscular dystrophy).
    • Mitochondrial Inheritance: Mutations in the mitochondrial DNA, inherited from the mother, can lead to conditions like Leigh syndrome.

Common Neurogenetic Disorders:

1. Huntington’s Disease:
 Definition: Neurodegenerative disease due to an autosomal dominant mutation of the HTT gene, resulting in the abnormal accumulation of huntingtin protein.
Symptoms: Includes chorea (involuntary movements), decreased mental status, depression, or irritability.
Inheritance: Autosomal dominant.
Management: Only symptomatic treatment. There is no cure. Medication is used to control movements and psychiatric symptoms.
 

2. Spinal Muscular Atrophy (SMA):
Description: A genetic disorder due to mutations in the SMN1 gene involving motor neurons, causing progressive muscle weakness and atrophy.
Symptoms: Muscle weakness, difficulty swallowing, respiratory issues, and mobility problems. The extent varies depending upon the type of SMA.
Inheritance: Autosomal recessive.
Treatment: With new therapies, including Spinraza (nusinersen), gene therapy (Zolgensma), and Evrysdi (risdiplam), the outcomes have improved significantly.

3. Fragile X Syndrome:
Description: It is the most common form of inherited intellectual disability; in this case, the mutation affects the FMR1 gene located on the X chromosome .
Symptoms: Late mixed developmental delay, intellectual disability; a lots of anxiety, ADHD, and even autistic-like behaviors; elongated face and big ears .
Inheritance: Dominant X-linked.
Treatment: The cure doesn’t exist; yet, therapies could really improve the child’s behavioral and development progressions.

4. Rett Syndrome:
Description: A rare neurodevelopmental disorder involving mutated forms of the MECP2 gene, affecting mostly females.
Symptoms: Loss of motor skills, speech impairment, convulsions, and stereotypic hand movements (hand-wringing, for example).
Inheritance: Usually occurs as a de novo mutation.
Treatment: Management of symptoms with physical, occupational therapy, and medications to control seizures.

5. Duchenne Muscular Dystrophy (DMD):
Definition: A genetic disease that causes severe muscular weakness and degeneration. It is due to mutations in the dystrophin gene.
Symptoms: Muscle weakness usually starts in the first decade of life, followed by rapid progression to involve the muscles of the heart and respiratory systems.
Inheritance: X-linked recessive.
Treatment: Corticosteroids can be used to slow progression, and newer gene therapies are still in development.

6. Charcot-Marie-Tooth Disease (CMT):
Definition: A hereditary, peripheral neuropathy affecting motor and sensory nerves, leading to muscle atrophy, weakness, and loss of sensation.
Symptoms: Weakness in legs, feet, and hands, foot deformities, and problems with walking.
Inheritance: Autosomal dominant, autosomal recessive, or X-linked.
Treatment: PT, orthopedic appliances, and pain treatment but there is no cure for this.

7. Neurofibromatosis (NF):
This is a condition where various neurological and developmental syndromes are caused by the formation of tumors along the nerve tissues. The two common types are NF1 and NF2.
Symptoms: Skin, brain, and spinal cord tumors, learning disabilities, and visual abnormalities.
Inheritance: Autosomal dominant.
Treatment: Periodic follow-up and surgical debridements of the tumors. Therapeutic agents that inhibit tumor growth are currently being explored.

Diagnosis in Neurogenetics:

  • Genetic Testing:
    • Techniques like whole-exome sequencing (WES) or whole-genome sequencing (WGS) are used to identify mutations responsible for neurogenetic disorders.
    • Targeted testing for specific gene mutations is common for known conditions like Huntington’s or SMA.
  • Neuroimaging:
    • MRI or CT scans may be used to visualize structural abnormalities in the brain or spinal cord that are associated with genetic conditions.
  • Electrophysiology:
    • Techniques such as EEG (for epilepsy) or EMG (for muscular disorders) help assess the electrical activity of the brain or muscles.
  • Prenatal Testing:
    • For families with a known risk of genetic disorders, prenatal genetic testing (e.g., amniocentesis, chorionic villus sampling) can detect mutations in the fetus.

How has neurogenetics developed as a field of medicine?

The landmark event was completion of the Human Genome Project in 2003. The whole exome sequencing targeting disease-related portions of DNA then became a feasible proposition. The research DNA from many affected individuals now allowed the identification of patterns of genetic expression. This led to tremendous success in neurogenetics-the discovery of Alzheimer’s, Parkinson’s, Huntington’s, and Multiple Sclerosis associated genes.

At our Neurosys Multispeciality  Center, we perform several key procedures including Craniotomy, which is primarily for the excision of brain tumors; V-P Shunt Surgery for treating hydrocephalus; surgeries for epilepsy; and operations targeting brain stem glioma. Beyond these, we offer a range of other neurosurgical services. If you have any questions that are not answere, please contact us through our Contact Us or Book your Appointment.