SNP Shot: Genomic Insights

Pelizaeus-Merzbacher-like disease type 1 (PMLD1) is a genetic disorder affecting the brain and spinal cord (central nervous system). It belongs to a group of inherited diseases called leukodystrophies, which disrupt the white matter of the nervous system. White matter is composed of nerve fibers insulated by myelin, a fatty substance crucial for rapid nerve impulse transmission. In PMLD1, the body's ability to produce myelin is significantly reduced, a condition known as hypomyelination. While its symptoms are similar to Pelizaeus-Merzbacher disease (PMD), PMLD1 has a different genetic cause.

Infants with PMLD1 usually exhibit symptoms within the first few months of life. These include weak muscle tone (hypotonia), involuntary eye movements (nystagmus), and delays in developmental milestones like speech and motor skills (e.g., sitting and grasping). As children age, their initial hypotonia typically progresses to muscle stiffness (spasticity).

Later in childhood, individuals with PMLD1 develop difficulties with movement and balance (ataxia), problems judging distances or scale when moving (dysmetria), tremors that worsen during movement (intention tremors), and head and neck tremors (titubation). They may also struggle with rapid, alternating movements (dysdiadochokinesia), such as finger tapping. Some individuals experience involuntary muscle contractions (dystonia) and jerky (choreiform) movements. Skeletal problems, such as scoliosis (spinal curvature), are common, often leading to the need for wheelchair assistance from childhood.

Muscle issues can cause difficulties swallowing and with expressive language (speaking), but individuals typically retain the ability to understand speech (receptive language). Cognitive function is usually normal in people with PMLD1. In rare cases, hearing loss, optic atrophy (degeneration of the optic nerve), and recurrent seizures (epilepsy) may occur.

Inheritance:

PMLD1 follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. Parents who each carry one copy of the mutated gene are typically asymptomatic carriers.