SNP Shot: Genomic Insights

Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a type of hereditary spastic paraplegia (HSP), a group of genetic disorders marked by progressive muscle stiffness (spasticity) and eventual paralysis (paraplegia) of the legs. This spasticity and paraplegia stem from the deterioration (atrophy) of motor neurons, the nerve cells in the brain and spinal cord that control muscle movement. HSPs are classified as either pure or complicated. Pure HSPs affect only the lower limbs, while complicated HSPs involve other parts of the nervous system, impacting the upper limbs and other areas. IAHSP begins as a pure HSP, with leg spasticity and weakness, but as it progresses, the arms, neck, and head become involved, displaying characteristics more typical of a complicated HSP.

Infants with IAHSP usually appear normal at birth, with the first symptoms appearing within the first two years of life. These early symptoms include exaggerated reflexes (hyperreflexia) and recurring muscle spasms in the legs. As the disease progresses, children develop abnormal tightness and stiffness in their leg muscles, as well as weakness in both their legs and arms. Over time, this muscle weakness and stiffness spreads upwards (ascends) from the legs to the head and neck. Weakness in the head and neck muscles typically develops during adolescence, leading to slow eye movements and difficulties with speech and swallowing. Affected individuals may eventually lose the ability to speak entirely (anarthria). The weakness in the leg and arm muscles can become severe enough to cause paralysis, often requiring wheelchair assistance by late childhood or early adolescence. Notably, intelligence remains unaffected in individuals with IAHSP.

Juvenile primary lateral sclerosis shares many characteristics with IAHSP. Both conditions are caused by the same genetic defect and significantly impair movement starting in childhood. However, the pattern of nerve cell degeneration differs between the two. Due to these similarities, IAHSP and juvenile primary lateral sclerosis are sometimes considered to be the same disorder.

Inheritance:

IAHSP 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 only one copy of the mutated gene typically do not exhibit any signs or symptoms of the disorder.