SNP Shot: Genomic Insights

Silver syndrome is a type of hereditary spastic paraplegia (HSP), a group of inherited conditions causing progressive muscle stiffness (spasticity) and often leading to lower limb paralysis (paraplegia). HSPs are classified as either pure or complex. Both types affect the legs, but complex HSPs can also involve the arms, though usually less severely. Complex HSPs may also affect the brain and parts of the nervous system that control movement and sensation. Silver syndrome falls under the category of complex hereditary spastic paraplegias.

Typically, the initial symptom of Silver syndrome is muscle weakness in the hands. This weakness leads to muscle wasting (amyotrophy), causing abnormal thumb positioning and difficulty with fine motor skills like handwriting. Individuals with Silver syndrome often exhibit high-arched feet (pes cavus) and spasticity in their legs. The onset of these signs and symptoms typically occurs in late childhood, but can range from early childhood to late adulthood. While the muscle problems associated with Silver syndrome gradually worsen over time, affected individuals generally maintain an active lifestyle throughout their lives.

Inheritance:

Silver syndrome is typically inherited in an autosomal dominant manner. This means that only one copy of the mutated gene in each cell is needed to cause the disorder. In these cases, an affected individual inherits the mutation from one parent who also has the condition. However, some individuals who inherit the mutated gene may never develop the symptoms of Silver syndrome, a phenomenon known as reduced penetrance. The reason for this variability in symptom expression is currently unknown. In rare instances, Silver syndrome can result from a new (de novo) mutation in the gene, occurring in individuals with no prior family history of the disorder.