Spastic paraplegia 7

Alternate names

SPG7; Hereditary spastic paraplegia Paraplegin type

Definition

Spastic paraplegia type 7 (also called SPG7) is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) in the legs and difficulty walking.

Summary

• Hereditary spastic paraplegias are divided into two types: pure and complex.
• The pure types generally involve only spasticity of the lower limbs and walking difficulties.
• The complex types involve more widespread problems with the nervous system; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). In complex forms, there can also be features outside of the nervous system.
• Spastic paraplegia type 7 can occur in either the pure or complex form.

Epidemiology

The prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people worldwide. Spastic paraplegia type 7 likely accounts for only a small percentage of all spastic paraplegia cases.

Cause

• Mutations in the SPG7 gene cause spastic paraplegia type 7. The SPG7 gene provides instructions for producing a protein called paraplegin. Located within the inner membrane of the energy-producing centers of cells (mitochondria), paraplegin is one of the proteins that form a complex called the m-AAA protease.
• The m-AAA protease acts as an enzyme and is responsible for assembling ribosomes (cellular structures that process the cell's genetic instructions to create proteins) and removing nonfunctional proteins in the mitochondria.
• When there is a mutation in paraplegin, the m-AAA protease cannot function correctly. Nonfunctional m-AAA proteases cause a build up of unusable proteins in the mitochondria of nerve cells, which can result in swelling of the cell, reduced cell signaling, and impaired cell movement, leading to the major signs and symptoms of spastic paraplegia type 7.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Onset

The onset of symptoms varies greatly among those with spastic paraplegia type 7; however, abnormalities in muscle tone and other features usually become noticeable in adulthood.

Signs and symptoms

Like all hereditary spastic paraplegias, spastic paraplegia type 7 involves spasticity of the leg muscles and some muscle weakness. People with this form of spastic paraplegia can also have ataxia; a pattern of movement abnormalities known as parkinsonism; exaggerated reflexes (hyperreflexia) in the arms; speech difficulties (dysarthria); difficulty swallowing (dysphagia); involuntary movements of the eyes (nystagmus); mild hearing loss; abnormal curvature of the spine (scoliosis); high-arched feet (pes cavus); numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); and muscle wasting (amyotrophy).

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms Spastic gait(Spastic walk)

30%-79% of people have these symptoms

• Abnormal mitochondrial morphology
• Attention deficit hyperactivity disorder(Attention deficit)
• Babinski sign
• Cerebellar atrophy(Degeneration of cerebellum)
• Impaired vibration sensation in the lower limbs(Decreased lower limb vibratory sense)
• Lower limb hyperreflexia(Overactive lower leg reflex)
• Lower limb hypertonia
• Lower limb muscle weakness(Lower extremity weakness)
• Nasal speech(Nasal voice)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Optic atrophy
• Ragged-red muscle fibers
• Slowed slurred speech
• Supranuclear gaze palsy
• Urinary urgency(Overactive bladder)

5%-29% of people have these symptoms

• Abnormality of the cerebral white matter
• Cerebral cortical atrophy(Decrease in size of the outer layer of the brain due to loss of brain cells)
• Dysarthria(Difficulty articulating speech)
• Optic disc pallor
• Pes cavus(High-arched foot)
• Scoliosis
• Upper limb muscle weakness(Decreased arm strength)

1%-4% of people have these symptoms

• Dysphagia(Poor swallowing)
• Lower limb pain(Leg pain)
• Memory impairment(Forgetfulness)
• Specific learning disability

Diagnosis

Spastic paraplegia 7 (SPG7) should be suspected in individuals with the following:[1].

• Insidiously progressive bilateral leg weakness
• Spasticity
• Decreased vibratory sense
• Cerebellar signs

Neurologic examination demonstrating EITHER of the following:

• A pure phenotype of spastic paraplegia with hyperreflexia, extensor plantar responses, and mildly impaired vibration sensation in the distal legs
• A complicated phenotype of spastic paraplegia including optic neuropathy, progressive external ophthalmoplegia/ptosis slowed speech, swallowing difficulties, palatal tremor, subtle cognitive impairment, urinary urgency, ataxia, nystagmus, strabismus, decreased hearing, scoliosis, pes cavus, motor and sensory neuropathy, and amyotrophy.
• Neuroimaging findings of cerebellar atrophy (MRI) or white matter changes as detected by diffusion tensor imaging in the frontal lobes, the corticospinal tracts, and the brain stem
• Family history consistent with autosomal recessive inheritance

The diagnosis of SPG 7 is established in a proband with typical clinical findings and identification of biallelic pathogenic variants in SPG7 by molecular genetic testing.

Treatment

• No specific drug treatments or cures for SPG7 exist.
• Drugs to reduce spasticity and muscle tightness include baclofen, tizanidine, dantrolene, and diazepam – preferably administered one at a time.
• Management of spasticity by intrathecal baclofen or intramuscular botulinum toxin injections may be an option in selected individuals .
• A combination of physical therapy and assistive walking devices are often used to reduce contractures, provide support, and promote stability.
• Occupational therapy and speech therapy are often helpful in managing activities of daily living.

Prevention of Secondary Complications Because individuals with advanced disease are bedridden they are at major risk of aspiration pneumonia, urinary tract infections and pulmonary embolism; careful monitoring is recommended to help avoid these complications.

NIH genetic and rare disease info

• NIH info on Spastic paraplegia 7

Spastic paraplegia 7 is a rare disease.

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