Since Silver syndrome worsens over time, what can be done to manage symptoms and maintain quality of life?

While symptoms slowly worsen, individuals can remain active throughout life with appropriate management. This often involves physical and occupational therapy to help maintain muscle strength, flexibility, and fine motor skills in the hands and legs. Assistive devices may also be used as needed.

Is Silver syndrome inherited, and what are the chances of passing it on to my children?

Yes, Silver syndrome is a genetic disorder caused by mutations in the BSCL2 gene. It is typically inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene is needed to cause the condition. If a parent has Silver syndrome, there is a 50% chance with each pregnancy that their child will inherit the condition. Genetic counseling can provide more specific risk assessments.

What are the first signs of Silver syndrome parents or caregivers should watch for in a child?

The earliest signs typically appear in late childhood and include weakness in the muscles of the hands, which can lead to difficulty with fine motor tasks like handwriting. You might also notice abnormal positioning of the thumbs, high-arched feet (pes cavus), and muscle stiffness (spasticity) in the legs.

Silver syndrome

Silver syndrome is a rare genetic disorder characterized by progressive muscle stiffness and weakness, primarily affecting the hands and legs, typically beginning in late childhood.

Overview

Silver syndrome belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and, frequently, development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. Both types involve the lower limbs; the complex types may also involve the upper limbs, although to a lesser degree. In addition, the complex types may affect the brain and parts of the nervous system involved in muscle movement and sensations. Silver syndrome is a complex hereditary spastic paraplegia.

Although Silver syndrome appears to be a rare condition, its exact prevalence is unknown.

Symptoms

The first sign of Silver syndrome is usually weakness in the muscles of the hands. These muscles waste away (amyotrophy), resulting in abnormal positioning of the thumbs and difficulty using the fingers and hands for tasks such as handwriting. People with Silver syndrome often have high-arched feet (pes cavus) and spasticity in the legs. The signs and symptoms of Silver syndrome typically begin in late childhood but can start anytime from early childhood to late adulthood. The muscle problems associated with Silver syndrome slowly worsen with age, but affected individuals can remain active throughout life.

Causes

Mutations in the BSCL2 gene cause Silver syndrome. The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. The BSCL2 gene is active (expressed) in cells throughout the body, particularly in nerve cells that control muscle movement and in brain cells. Within cells, seipin is found in the membrane of a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport.

BSCL2 gene mutations that cause Silver syndrome likely lead to an alteration in the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness and spasticity. In Silver syndrome, only specific motor neurons are involved, resulting in the hand and leg muscles being solely affected.

Some people with Silver syndrome do not have an identified mutation in the BSCL2 gene. The cause of the condition in these individuals is unknown.

Inheritance

Silver syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, the affected person inherits the mutation from an affected parent. However, some people who inherit the altered gene never develop features of Silver syndrome. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not.

Rarely, Silver syndrome is caused by new (de novo) mutations in the gene and occurs in people with no history of the disorder in their family.

Other Names

Silver spastic paraplegia syndrome
Spastic paraplegia 17
Spastic paraplegia with amyotrophy of hands and feet
SPG17