4H Leukodystrophy
Description
4H leukodystrophy, also known as hypomyelination, hypodontia, hypogonadism, and hypoacusis, is a rare genetic disorder primarily affecting the brain‘s white matter, which is responsible for transmitting signals between different parts of the brain. This disorder can lead to a range of neurological problems, impacting motor skills, speech, hearing, and overall development.
Genes Involved
4H leukodystrophy is caused by mutations in genes responsible for the production of myelin, the protective sheath surrounding nerve fibers. The most commonly affected genes include:
- MYSB2: This gene provides instructions for making a protein involved in the formation of myelin in the brain and spinal cord. Mutations in this gene are the most common cause of 4H leukodystrophy.
- MFN2: This gene is responsible for a protein that plays a critical role in mitochondrial function. Mitochondrial dysfunction can disrupt myelin production and lead to the symptoms of 4H leukodystrophy.
- Other Genes: Other genes that have been linked to 4H leukodystrophy include PMP22, MPZ, GJB1, and L1CAM.
Recognizing the Signs and Symptoms
The symptoms of 4H leukodystrophy often appear in early childhood and can vary widely in severity. Some common signs include:
- Developmental delays: Delayed milestones in speech, motor skills, and cognitive development.
- Hypomyelination: Reduced or abnormal myelin, the protective sheath surrounding nerve fibers, leading to impaired nerve conduction.
- Hypodontia: Missing or underdeveloped teeth.
- Hypogonadism: Delayed or incomplete sexual development.
- Hypoacusis: Hearing loss.
- Seizures: Recurrent episodes of abnormal brain activity.
- Cerebral palsy: A disorder affecting muscle movement and coordination.
- Vision problems: Impaired vision or eye movements.
- Behavioral issues: Attention deficit, hyperactivity, or autism spectrum disorder.
Causes
4H leukodystrophy is a genetic disorder, meaning it is caused by mutations in certain genes. These mutations are passed down from parents to children. In some cases, a new mutation can occur spontaneously, without a family history of the disorder.
Inheritance/recurrence risk
4H leukodystrophy can be inherited in an autosomal recessive pattern. This means that an individual needs to inherit two copies of the mutated gene, one from each parent, to develop the disorder. If both parents carry one copy of the mutated gene, there is a 25% chance that their child will inherit two copies and develop the disorder. There is a 50% chance that their child will inherit one copy and be a carrier of the gene. There is a 25% chance that their child will inherit no copies of the mutated gene and will not develop the disorder.
