SNP Shot: Genomic Insights

Spastic paraplegia type 2 (SPG2) belongs to a group of inherited disorders known as hereditary spastic paraplegias (HSPs). These disorders are characterized by progressive stiffness in the muscles (spasticity) and gradual paralysis of the legs (paraplegia). HSPs are classified as either "pure" or "complex." Pure HSPs primarily affect the lower limbs, while complex HSPs affect the lower limbs and may also impact the upper limbs to a lesser degree, the brain's structure or function, and the peripheral nervous system (nerves connecting the brain and spinal cord to muscles and sensory cells). SPG2 can manifest in either the pure or complex form.

Individuals with pure SPG2 typically experience spasticity in their legs without other significant symptoms. Those with complex SPG2 have leg spasticity and may also experience difficulties with coordination and balance (ataxia), involuntary eye movements (nystagmus), mild intellectual disability, tremors (involuntary shaking), and optic nerve atrophy (degeneration of the nerves that transmit visual information to the brain). Symptoms usually appear between 1 and 5 years of age. Affected individuals are typically able to walk and have a normal life expectancy.

Inheritance:

SPG2 is inherited in an X-linked recessive pattern. X-linked conditions are caused by a mutated gene located on the X chromosome, one of the sex chromosomes. Males, who have only one X chromosome, will develop the condition if they inherit one altered copy of the gene. Females have two X chromosomes, so usually one altered copy results in milder symptoms or no symptoms at all compared to males. A key feature of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one altered copy of the gene is called a carrier. She can pass the gene on to her children, but typically does not show signs and symptoms of the disorder. However, some female carriers of a PLP1 mutation may experience muscle stiffness and decreased intellectual function. Furthermore, females with one PLP1 mutation have an increased risk of developing progressive cognitive decline (dementia) later in life.