Spastic paraplegia 4

Alternate names

SPG4; Autosomal dominant spastic paraplegia 4; Familial spastic paraplegia autosomal dominant 2; FSP2

Definition

Spastic paraplegia 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) inherited in an autosomal dominant manner.

Cause

SPG4 is caused by mutations in the SPAST gene.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

SPG4 is inherited in an autosomal dominant manner.

• This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.
• In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.
• When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Onset

• Disease onset ranges from infancy to older adulthood.
• Signs and symptoms of SPG4 usually become apparent in young adulthood; although symptoms may start as early as one year of age and as late as 76 years.

Signs and symptoms

Characteristic symptoms include stiff and rigid muscles (spasticity) and weakness in both of the legs and the lower portion of the body. Additional symptoms are different for every affected individual. Other symptoms may include:

• Decreased ability to sense vibrations in the ankles
• Exaggerated reflexes (hyperreflexia)
• Ankle spasms
• High arches in the feet (pes cavus)
• Reduced bladder control
• Ataxia (lack of muscle control)
• Seizures
• Some individuals may also experience a mild decline in cognitive function. This decline does not typically affect daily functioning.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Ankle clonus(Abnormal rhythmic movements of ankle)
• Babinski sign
• Brisk reflexes
• Functional motor deficit
• Impaired vibration sensation at ankles(Decreased vibration sense at ankles)
• Leg muscle stiffness
• Lower limb muscle weakness(Lower extremity weakness)
• Lower limb spasticity
• Urinary urgency(Overactive bladder)

5%-29% of people have these symptoms

• Cognitive impairment(Abnormality of cognition)
• Distal amyotrophy(Distal muscle wasting)
• Dysarthria(Difficulty articulating speech)
• Hyperreflexia in upper limbs
• Pes cavus(High-arched foot)
• Urinary bladder sphincter dysfunction

1%-4% of people have these symptoms

• Ataxia
• Intellectual disability(Mental deficiency)
• Seizure

Diagnosis

The diagnosis of SPAST-HSP is established in a proband with characteristic clinical features and a heterozygous pathogenic variant in SPAST identified by molecular genetic testing.[https:/www.ncbi.nlm.nih.gov/books/NBK1160//].

Treatment

Care for SPG4 is usually managed by a team including a primary care physician, neurologist, genetics professional (geneticist and/or genetic counselor), physical therapist, social worker, and psychologist. Treatment is focused on alleviating symptoms and may include:

• Medications for leg spasticity (antispastic drugs)
• Medications to assist in bladder control (anticholinergic antispasmodic drugs)
• Regular physician therapy
• Botulinum toxin and intrathecal baclofen for severe spasticity

Prognosis

The severity of symptoms in SPG4 generally worsen over time; however, some individuals may have mild symptoms throughout their lives. Approximately 17% of individuals eventually use a wheelchair, while approximately 20% use assistance (such as a walker) to walk.

NIH genetic and rare disease info

• NIH info on Spastic paraplegia 4

Spastic paraplegia 4 is a rare disease.

Spastic paraplegia 4 Resources
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