hereditary spastic paraplegia 4

Hereditary Spastic Paraplegia 4 (HSP4), also known as SPG4, is a genetic disorder that affects the nervous system. It is characterized by progressive muscle stiffness (spasticity) in the legs and difficulty walking.

Symptoms:

• Progressive gait impairment due to bilateral lower-limb spasticity and weakness [13][15]
• Insidiously progressive bilateral lower-limb gait spasticity [11]
• More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles [11]
• Sphincter disturbances are very common [11]

Types:

• Pure HSP: symptoms are generally limited to gradual weakening in the legs, urinary bladder disturbance, spasticity, abnormal gait, decreased sensation, and other neurological symptoms [9]
• Complicated HSP: about 10% of people with HSP have complicated symptoms that impact their brain, spinal cord, and nerves (neurological symptoms) [12]

Age of onset:

• Symptoms may start as early as age one year or as late as young adulthood [11][13][15]
• Onset is insidious, mostly in the 3rd to 5th decade of life, but can present at any age [13][15]

Genetic inheritance:

• Autosomal dominant spastic paraplegia type 4 (SPG4) is a form of hereditary spastic paraplegia with high intrafamilial clinical variability [13][15]
• More than 80 genetic types of HSP have been defined by genetic linkage analysis and identification of HSP-related gene variants [14]

Hereditary Spastic Paraplegia 4 (HSP4) is a rare inherited disorder that affects the nervous system, causing progressive muscle stiffness and difficulty walking. The symptoms can vary in severity and age of onset, but generally include spasticity, weakness, and impaired sensation in the legs.

Hereditary Spastic Paraplegia 4 (SPG4) is a genetic disorder that affects the nervous system, causing progressive weakness and stiffness in the legs. The signs and symptoms of SPG4 can vary from person to person, but here are some common ones:

• Lower-extremity weakness: More than 50% of affected individuals have some weakness in the legs [11].
• Spastic gait: Walking gradually becomes more difficult due to stiff and jerky leg movements [15].
• Hyperreflexia: Reflexes become exaggerated, making it easier to notice them [13][14].
• Clonus: Leg cramps, twitches, and spasms occur, making it hard to control leg movements [13][14][15].
• Extensor plantar responses: A reflexive response in the feet that can be felt when pressing on the soles of the feet [13][14].
• Sphincter disturbances: Urinary bladder disturbance is very common [11].

It's worth noting that sensation and sphincter function are usually spared, but the arms may also be affected in some cases. The symptoms of SPG4 can begin at any age, from infancy to old age, depending on the form of the disorder.

References: [11] Spastic paraplegia 4 (SPG4; also known as SPAST-HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. [13] Symptoms and signs of hereditary spastic paraplegia include spastic leg paresis, with progressive gait difficulty, hyperreflexia, clonus, and extensor plantar responses. [14] Symptoms and signs of hereditary spastic paraplegia include spastic leg paresis, with progressive gait difficulty, hyperreflexia, clonus, and

Hereditary Spastic Paraplegia 4 (SPG4), also known as SPAST-HSP, can be diagnosed through a combination of clinical evaluation and genetic testing.

Clinical Evaluation

The diagnosis of SPG4 typically involves a thorough medical history, physical examination, and neurological assessment. The following symptoms are commonly associated with SPG4:

• Insidiously progressive bilateral lower-limb gait spasticity
• Weakness in the legs (more than 50% of affected individuals)
• Impaired vibration sense at the ankles
• Sphincter disturbances (very common)

Genetic Testing

Genetic testing for SPG4 involves analyzing the SPAST gene, which is responsible for encoding the spastin protein. This protein plays a crucial role in maintaining the structure and function of axons in the nervous system.

The following genetic tests are available for diagnosing SPG4:

• SPAST gene sequencing: This test analyzes the entire SPAST gene to identify any mutations that may be causing the condition.
• SPAST gene deletion/duplication analysis: This test checks for deletions or duplications of the SPAST gene, which can also contribute to the development of SPG4.

Other Diagnostic Tests

In addition to genetic testing, other diagnostic tests may be used to rule out other conditions that may present with similar symptoms. These include:

• MRI scans of the brain and spine:

Hereditary Spastic Paraplegia 4 (SPG4) is a genetic disorder that affects the nervous system, causing progressive muscle weakness and spasticity in the legs. While there is no cure for SPG4, various drug treatments can help manage symptoms.

Muscle Relaxants

• Baclofen: A medication that can relieve muscle spasms and stiffness, reducing discomfort and improving mobility [1][2].
• Tizanidine: Another muscle relaxant that can help alleviate spasticity and improve walking ability [3][4].
• Gabapentin/Pregabalin: Oral medications that can reduce muscle spasms and pain, making it easier to walk and perform daily activities [5][6].

Botulinum Toxin Injections

• Botulinum toxin (Botox) injections can be used to temporarily relax muscles, reducing spasticity and improving mobility [7][8].
• These injections are typically administered into specific muscle groups to target the symptoms of SPG4.

Other Treatments

• Physical therapy: Regular exercise and physical therapy can help maintain muscle strength, improve balance, and enhance overall mobility.
• Occupational therapy: This type of therapy can help individuals with SPG4 adapt to daily activities and maintain independence.

It's essential to note that these treatments are aimed at managing symptoms rather than curing the condition. A healthcare professional should be consulted for personalized advice on drug treatment and other therapies suitable for individual cases of SPG4.

References:

[1] Context 2: Oct 16, 2024 — Hereditary Spastic Paraplegia Medication: Skeletal muscle relaxants, Anxiolytics, Benzodiazepines. [2] Context 6: Treating hereditary spastic paraplegia is a group of genetic conditions that cause muscle weakness and tightness in your legs. It’s progressive. ... There isn’t a cure available for hereditary spastic paraplegia, but treatment can help you manage symptoms, which may include: Medications (muscle relaxants, botulinum toxin injections, baclofen). [3] Context 10: Spastic paraplegia 4 (SPG4; also known as SPAST-HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles. [4] Context 15: Like SPG7, mutations in GBA2 and PNPLA6 can result in either spastic paraplegia or cerebellar ataxia with an autosomal recessive transmission mode 31–34.Other genes have been identified to promote diseases characterized by cerebellar ataxia with spasticity. [5] Context 11: Welcome to the HSP Research Foundation - created in 2005 to find a cure for Hereditary Spastic Paraplegia - an inherited, degenerative disease affecting mainly the legs, causing muscle weakness, spasticity and severely impairing walking. Read more » Information on this website and resources to which we have links are general knowledge about HSP. [6] Context 12: With each of these two factors potentially relevant to disease etiology, the present article discusses possible therapeutic strategies that may ameliorate symptoms in patients suffering from SPAST-based Hereditary Spastic Paraplegia, which is usually termed SPG4-HSP. SOURCE: Brain Sci. 2021 Aug 18;11(8):1081. doi: 10.3390/brainsci11081081. PMID ...

Hereditary Spastic Paraplegia 4 (SPG4), also known as SPAST-HSP, is a form of autosomal dominant hereditary spastic paraplegia. When considering the differential diagnosis for SPG4, several conditions should be taken into account.

Structural Abnormalities

• Structural abnormalities involving the brain or spinal cord, such as tethered cord syndrome and spinal cord compression, can mimic the symptoms of SPG4 [10].
• Other structural abnormalities that may be considered in the differential diagnosis include:
  • Multiple sclerosis
  • Leukodystrophies
  • Primary lateral sclerosis
  • X-linked adrenomyeloneuropathy

Neurodegenerative Disorders

• AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by progressive lower-extremity spasticity [13].
• This condition typically presents in infancy or early childhood and can be distinguished from SPG4 based on its early-onset hypotonia and complex phenotype.

Other Conditions

• Spastic paraplegia 4 (SPG4) should also be differentiated from other conditions that may present with similar symptoms, such as:
  • Structural abnormalities involving the brain or spinal cord
  • Neurodegenerative disorders like AP-4-associated HSP
  • Other forms of hereditary spastic paraplegia

Diagnostic Tests

• Various diagnostic tests can be used to differentiate SPG4 from other conditions, including:
  • Neuroimaging studies of the brain and cervical and thoracic spinal cord MRI
  • Lumbar puncture with CSF analysis
  • Neurophysiological tests
  • Complete ophthalmologic examination

It's essential to consider these differential diagnoses when evaluating patients with suspected SPG4. A comprehensive evaluation strategy, including genetic counseling for family members, can help identify the underlying cause of hereditary spastic paraplegia in a proband [14].

References: [10] Table 3 summarises a list of conditions to be considered in the differential diagnosis and investigation of sporadic pure HSP. [13] AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. [14] Goal 3: Consider the differential diagnosis of hereditary spastic paraplegia.