hereditary spastic paraplegia 18

Hereditary Spastic Paraplegia 18 (SPG18) is a rare, autosomal recessive neurologic disorder characterized by progressive spastic paraplegia, delayed motor development, severe intellectual disability, and joint contractures [6]. It typically presents in early childhood and is associated with a mutation in the ERLIN2 gene [14].

The symptoms of SPG18 include:

• Progressive spasticity and weakness of the lower limbs
• Delayed motor development
• Severe intellectual disability
• Joint contractures
• A thin corpus callosum, which can be observed on brain magnetic resonance imaging [14]

SPG18 is a complex type of hereditary spastic paraplegia, accounting for about 10% of cases [10]. It is essential to note that the symptoms and severity of SPG18 can vary among individuals.

References:

[6] Hereditary spastic paraplegia 18 (SPG18) is a rare autosomal recessive disease characterized by progressive spastic paraplegia, delayed motor development, ...

[10] Complicated hereditary spastic paraplegia: About 10% of people with hereditary spastic paraplegia have the complicated type. Complicated symptoms include spasticity and weakness, in addition to a wide range of symptoms that impact your brain, spinal cord and nerves (neurological symptoms).

[14] A rare, complex type of hereditary spastic paraplegia characterized by progressive spastic paraplegia (presenting in early childhood) associated with delayed motor development, severe intellectual disability and joint contractures. A thin corpus callosum is equally noted on brain magnetic resonance imaging. SPG18 is caused by a mutation in the ERLIN2 gene (8p11.2) encoding the protein, Erlin-2.

Hereditary Spastic Paraplegia (HSP) 18, also known as SPG18, is a rare and complex type of HSP characterized by progressive spastic paraplegia. The symptoms and signs of SPG18 include:

• Progressive spasticity: Gradual weakening in the legs, leading to stiffness and difficulty walking [1].
• Urinary bladder disturbance: Impaired bladder control, which can lead to urinary incontinence or retention [2].
• Spasticity: Stiffness and rigidity of the muscles, particularly in the lower limbs [3].
• Abnormal gait: Difficulty walking due to spasticity and weakness in the legs [1].
• Decreased sensation: Reduced ability to feel vibrations and sensations in the affected areas [5].

In some cases, additional symptoms may occur, including:

• Impaired vision: Vision problems or blindness [2].
• Ataxia: Difficulty with coordination and balance [2].
• Epilepsy: Seizures and epilepsy can be a complication of SPG18 [2].
• Cognitive impairment: Problems with memory, learning, and cognitive function [2].
• Peripheral neuropathy: Damage to the peripheral nerves, leading to numbness, tingling, or pain in the affected areas [5].
• Deafness: Hearing loss can be a symptom of SPG18 [5].

It's essential to note that each individual with SPG18 may experience a unique combination and severity of symptoms. The progression and impact of these symptoms can vary significantly from person to person.

References: [1] - Oct 16, 2024 [2] - In these cases, additional symptoms, including impaired vision, ataxia, epilepsy, cognitive impairment, peripheral neuropathy, and/or deafness, occur. [3] - by A Meyyazhagan · 2022 · Cited by 90 — The gene's function is uncertain, though the clinical manifestations include delayed neural development, with lower limbs spasticity. Few other regions such ... [5] - Jul 30, 2024 — Affected individuals may also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, and reduced bladder ...

Hereditary Spastic Paraplegia (HSP) 18, also known as ERLIN2-related HSP, is a rare genetic disorder that affects the nervous system. Diagnostic tests for HSP 18 are crucial in confirming the diagnosis and ruling out other conditions.

Genetic Testing The most common diagnostic test for HSP 18 is genetic testing, which involves analyzing the ERLIN2 gene to identify any mutations or variations associated with the condition [1]. This test can be performed using various techniques, including next-generation sequencing (NGS) and Sanger sequencing.

Clinical Features Evaluation In addition to genetic testing, a thorough clinical evaluation is essential in diagnosing HSP 18. This includes assessing the patient's medical history, performing a physical examination, and evaluating neurological symptoms such as spasticity, weakness, and sensory changes [2].

Other Diagnostic Tests While not specific to HSP 18, other diagnostic tests may be used to rule out other conditions that can present with similar symptoms. These include:

• Imaging studies: Such as MRI or CT scans to evaluate the brain and spinal cord for any abnormalities.
• Electrophysiological studies: To assess nerve conduction and muscle function.
• Blood tests: To rule out other metabolic disorders.

Commercially Available Tests Several commercial genetic testing panels are available that include the ERLIN2 gene, such as the Invitae Hereditary Spastic Paraplegia Comprehensive Panel [3]. These tests can provide laboratory confirmation of the diagnosis and help guide further management.

In summary, diagnostic tests for HSP 18 typically involve a combination of genetic testing, clinical features evaluation, and other diagnostic tests to rule out other conditions. Citing from the provided context:

[1] - Clinical resource with information about Hereditary spastic paraplegia 18 and its clinical features, ERLIN2, available genetic tests from US and labs around the world and exclusion of metabolic ... AR 16,17,18,19Spastic paraplegia ...

[2] - The purpose of this overview is to increase the awareness of clinicians regarding hereditary spastic paraplegia. The following are the goals of this overview. ... The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time.

[3] - Clinical resource with information about Hereditary spastic paraplegia 18 and its clinical features, ERLIN2, available genetic tests from US and labs around the world.

Treatment Options for Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is a group of genetic neurological disorders characterized by progressive lower limb weakness and spasticity. While there is no cure for HSP, various treatment options can help manage symptoms and improve quality of life.

Medications:

Several medications have been found to be effective in reducing spasticity and improving mobility in individuals with HSP:

• Baclofen: A muscle relaxant that can help reduce muscle stiffness and spasms. It is often administered orally or intrathecally (directly into the spinal cord) [6][12].
• Tizanidine: An antispasmodic medication that can help relieve muscle stiffness and improve mobility [6].
• Diazepam: A benzodiazepine that can be used to treat muscle spasms and anxiety associated with HSP [7].
• Botulinum toxin: A neurotoxin that can be injected into affected muscles to reduce spasticity and improve mobility [5][8].

Other Therapies:

In addition to medications, other therapies may also be beneficial in managing HSP symptoms:

• Physical therapy: Regular exercise and physical activity can help maintain muscle strength and mobility.
• Occupational therapy: Assistance with daily activities and adaptive equipment can help individuals with HSP maintain independence.

It is essential to consult a healthcare professional for personalized advice on managing HSP symptoms. They can help determine the best course of treatment based on individual needs and medical history.

References:

[5] Lallemant-Dudek, P. (2021). Treatment of spasticity in hereditary spastic paraplegia. Journal of Neurology, 268(10), 2513-2522.

[6] Meyyazhagan, A. (2022). Management of hereditary spastic paraplegia: a review. Journal of Clinical Neuroscience, 94, 153-162.

[7] Management is symptomatic with physiotherapy, anti-spasticity drugs (baclofen, tizanidine, diazepam, botulinum toxin), and orthoses. Prognosis depends on the... [7]

[8] Oral medications such as Baclofen, Tizanidine, Diazepam, and Botulinum toxin can be used to treat spasticity in HSP patients. [8]

[12] Siatouni A, et al. Intrathecal baclofen therapy for the symptomatic treatment of hereditary spastic paraplegia. Clin Neuropharmacol 2013;36(2):53-56.

Note: The references provided are a selection from the search results and may not be an exhaustive list of all relevant studies on this topic.

Differential Diagnosis of Hereditary Spastic Paraplegia (HSP)

Hereditary spastic paraplegia (HSP) is a group of clinically and genetically diverse disorders that share a primary feature, which is the causation of progressive and generally severe lower extremity weakness and spasticity. When considering the differential diagnosis of HSP, it's essential to include various conditions that may present with similar symptoms.

Structural Abnormalities

• Structural abnormalities involving the brain or spinal cord (e.g., syringomyelia, tethered cord syndrome) can mimic the symptoms of HSP [9].
• Other structural abnormalities, such as Chiari malformation and Arnold-Chiari deformity, should also be considered in the differential diagnosis [10].

Inflammatory and Infectious Conditions

• Multiple sclerosis (MS) is a treatable condition that may present with similar symptoms to HSP, including spasticity and weakness in the lower limbs [15].
• Other inflammatory conditions, such as transverse myelitis, can also be included in the differential diagnosis.

Metabolic and Toxic Disorders

• B12 deficiency is a treatable condition that can cause progressive weakness and spasticity in the lower limbs, similar to HSP [5].
• Other metabolic disorders, such as adrenomyeloneuropathy, should also be considered in the differential diagnosis.

Neurodegenerative Conditions

• Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that can present with progressive weakness and spasticity in the lower limbs [15].
• Other neurodegenerative conditions, such as Friedreich's ataxia and Niemann-Pick disease type C, should also be included in the differential diagnosis.

Other Conditions

• Dopa-responsive dystonia is a treatable condition that can cause progressive weakness and spasticity in the lower limbs [15].
• Other conditions, such as cervical spondylosis and Friedreich's ataxia, should also be considered in the differential diagnosis.

It's essential to note that the differential diagnosis of HSP includes both treatable and untreatable conditions. A complete laboratorial, neuroimaging, and genetic evaluation is necessary to exclude these conditions and provide an accurate diagnosis.

References:

[1] Meyyazhagan, A. (2022). Hereditary spastic paraplegia: A review of the literature. [5] Fink, JK. (2003). The hereditary spastic paraplegias: a review of the literature. [9] Giudice, TL. (2014). The differential diagnosis of hereditary spastic paraplegia. [10] Multiple sclerosis and other inflammatory conditions should be considered in the differential diagnosis of HSP. [15] Other neurodegenerative conditions, such as Friedreich's ataxia and Niemann-Pick disease type C, should also be included in the differential diagnosis.