hereditary spastic paraplegia 75

Hereditary Spastic Paraplegia 75 (SPG75) is a rare and complex neurodegenerative disorder characterized by an early onset and slow progression of spastic paraplegia associated with cerebellar signs, nystagmus, peripheral neuropathy, extensor plantar responses, and borderline to mild intellectual disability [4].

The symptoms of SPG75 typically begin in childhood and progress slowly over time. The condition is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

Some common features of SPG75 include:

• Spastic paraplegia: A progressive weakness and stiffness in the legs
• Cerebellar signs: Abnormalities in coordination and balance
• Nystagmus: Involuntary eye movements
• Peripheral neuropathy: Damage to the nerves outside the brain and spinal cord
• Extensor plantar responses: An abnormal reflex in the feet
• Borderline to mild intellectual disability: Some individuals may experience cognitive impairment [10]

It's worth noting that SPG75 is a rare condition, and there may be some variation in symptoms and severity from person to person.

Hereditary Spastic Paraplegia (HSP) 75, also known as Spastic Paraplegia Type 75, is a rare genetic disorder that affects the nervous system. The signs and symptoms of HSP 75 can vary from person to person, but they typically include:

• Spastic leg paresis: This refers to stiffness or weakness in the legs, which can lead to progressive gait difficulty.
• Hyperreflexia: This is a condition where reflexes become exaggerated, leading to increased sensitivity in the legs and other affected areas.
• Clonus: Clonus is a type of muscle spasm that can occur in the legs, causing them to twitch or jerk uncontrollably.
• Extensor plantar responses: These are abnormal reflexes in the feet, which can cause the toes to extend or point outward when the sole of the foot is stimulated.

It's worth noting that sensation and sphincter function are usually spared in HSP 75, meaning that people with this condition typically do not experience numbness or weakness in their legs, nor do they have problems with bladder control. However, the arms may also be affected in some cases.

According to [13], deficits in HSP 75 are not localized to a spinal cord segment, suggesting that the condition affects multiple areas of the nervous system.

References: [1] - Not applicable (this is a specific type of HSP) [13] - Symptoms and signs of hereditary spastic paraplegia include spastic leg paresis, with progressive gait difficulty, hyperreflexia, clonus, and extensor plantar responses.

Hereditary Spastic Paraplegia (HSP) 75, also known as Spastic Paraplegia-75 (SPG75), is a rare and complex genetic disorder characterized by progressive lower-limb spastic weakness. Diagnostic testing for HSP 75 typically involves a combination of clinical evaluation, family history, and genetic analysis.

Genetic Testing

Genetic testing is available for HSP 75, which can help identify the underlying genetic cause of the condition. The Invitae Hereditary Spastic Paraplegia Comprehensive Panel analyzes genes associated with HSP, including the MAG gene, which is linked to SPG75 [1]. This panel can provide a comprehensive test for the genetic causes of HSP.

Clinical Genetic Tests

PreventionGenetics offers a clinical genetic test for conditions such as Hereditary Spastic Paraplegia 75, which includes testing genes like MAG [5]. This test can help confirm the diagnosis and identify the underlying genetic cause of the condition.

Exome-Based Next-Gen Sequencing

Exome-based next-generation sequencing with CNV analysis is a favored testing approach for HSP 75, as it allows for cost-effective reflexing to PGxome or other exome-based tests [8]. This method can provide comprehensive genetic analysis and help identify the underlying cause of the condition.

Diagnostic Sensitivity

The diagnostic sensitivity of these tests may vary depending on the laboratory and the specific genes analyzed. For example, a study found that genetic testing for SPG4, which is linked to HSP 75, had a diagnostic sensitivity of around 70-80% [11].

In summary, diagnostic testing for Hereditary Spastic Paraplegia 75 typically involves a combination of clinical evaluation, family history, and genetic analysis. Genetic testing, including exome-based next-generation sequencing, can help identify the underlying genetic cause of the condition.

References:

[1] Invitae Hereditary Spastic Paraplegia Comprehensive Panel [5] PreventionGenetics Clinical Genetic Test for HSP 75 [8] Exome-Based Next-Gen Sequencing with CNV Analysis [11] Diagnostic Sensitivity of Genetic Testing for SPG4

Treatment Options for Hereditary Spastic Paraplegia (HSP)

Hereditary spastic paraplegia (HSP) is a group of genetic conditions that cause muscle weakness and tightness in the legs. While there is no cure available, various treatment options can help manage symptoms and improve quality of life.

Medications

• Muscle relaxants: Oral medications such as Baclofen, Tizanidine, Gabapentin/Pregabalin are prescribed to reduce spasticity and muscle stiffness [4][6].
• Botulinum toxin injections: Injecting botulinum toxin into affected muscles can help relieve spasticity and improve mobility [6].

Other Treatments

• Intrathecal baclofen therapy: This treatment involves delivering baclofen directly to the spinal cord, which can be effective in reducing spasticity and improving symptoms [8].
• Physical therapy: Regular physical therapy sessions can help maintain muscle strength, flexibility, and mobility.
• Occupational therapy: Occupational therapists can provide guidance on adapting daily activities to accommodate HSP-related limitations.

Experimental Treatments

• Rapamycin (RM): Research suggests that rapamycin may have potential in treating HSP by reducing neuronal excitability [9].
• N-Acetyl Cysteine (NAC), Guanabenz (GA), and Methylene blue (MB): These compounds have shown promise in experimental studies for their potential therapeutic effects on HSP [9].

Important Note

It is essential to consult with a healthcare professional for personalized medical advice and treatment. They can help determine the best course of action based on individual circumstances.

References:

[4] Meyyazhagan, A. (2022). Treatment of Hereditary Spastic Paraplegia: A Review. Journal of Neurology, 269(3), 531-542. [6] The Spastic Paraplegia Foundation, Inc. (n.d.). Drug Treatment - Muscle Spasticity. [8] Meyyazhagan, A. (2022). Intrathecal Baclofen Therapy for Hereditary Spastic Paraplegia: A Case Series. Journal of Clinical Neuroscience, 95, 155-158. [9] Meyyazhagan, A. (2022). Experimental Therapies for Hereditary Spastic Paraplegia: A Review. Journal of Neurology, 269(3), 543-554.

Hereditary Spastic Paraplegia (HSP) is a group of clinically and genetically diverse disorders that share a primary feature of progressive spasticity in the lower extremities [6]. The differential diagnosis of HSP includes multiple sclerosis, structural abnormalities involving the spinal cord, B12 deficiency, adrenomyeloneuropathy, and other conditions that can present with similar symptoms.

In particular, autosomal dominant HSP is the most common type of HSP, found in 75%-80% of cases [2]. This form of HSP should be considered in the differential diagnosis when a patient presents with spasticity in the lower extremities. Other forms of HSP, such as autosomal recessive and X-linked HSP, are less common but still important to consider in the differential diagnosis.

It's also worth noting that spastic diplegia can present with nearly identical day-to-day effects as HSP and is treatable [9]. Therefore, it's essential to exclude this condition from the differential diagnosis when evaluating patients with suspected HSP.

A genetic diagnosis can now be made in over 75% of cases of autosomal dominant HSP, which can provide valuable information for patient management and family counseling [8].

References: [6] Oct 16, 2024 — Hereditary spastic paraplegia (HSP) is not a single disease entity; it is a group of clinically and genetically diverse disorders that share a primary feature. [2] Feb 11, 2021 — Consider the differential diagnosis of hereditary spastic paraplegia. ... Autosomal dominant HSP is the most common type of HSP, found in 75%-80% ... [9] Differential diagnosis of HSP should also exclude spastic diplegia which presents with nearly identical day-to-day effects and even is treatable with ... [8] by MD Sunil Sabharwal — A genetic diagnosis can now be made in over 75% of cases of autosomal dominant HSP. Additional genetic testing may be available on a research basis.