hereditary spastic paraplegia 27

Hereditary Spastic Paraplegia 27 (HSP27) is a rare genetic disorder characterized by slowly progressive lower limb spasticity, hyperreflexia, and extensor plantar responses. This condition may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria, and mild to moderate intellectual disability.

The symptoms of HSP27 can vary in onset and severity, but typically include:

• Slowly progressive lower limb spasticity
• Hyperreflexia (increased reflexes)
• Extensor plantar responses (a sign of upper motor neuron dysfunction)
• Sensorimotor polyneuropathy (damage to both sensory and motor nerves)
• Decreased vibration sense
• Lower limb distal muscle wasting
• Dysarthria (speech difficulties)
• Mild to moderate intellectual disability

HSP27 is a rare condition, and its exact prevalence is unknown. However, it is estimated that about 10% of people with hereditary spastic paraplegia have the complicated type, which includes symptoms like those described above.

It's worth noting that HSP27 is a genetic disorder, meaning it is inherited in an autosomal recessive pattern. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

References:

• [1] A rare pure or complex hereditary spastic paraplegia with characteristics of variable onset of slowly progressive lower limb spasticity, hyperreflexia and extensor plantar responses, that may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria and mild to moderate intellectual disability.
• [12] A rare pure or complex hereditary spastic paraplegia with characteristics of variable onset of slowly progressive lower limb spasticity, hyperreflexia and extensor plantar responses, that may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria and mild to moderate intellectual disability.
• [13] A rare pure or complex hereditary spastic paraplegia with characteristics of variable onset of slowly progressive lower limb spasticity, hyperreflexia and extensor plantar responses, that may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria and mild to moderate intellectual disability.

Hereditary Spastic Paraplegia (HSP) type 27, also known as Autosomal Recessive Spastic Paraplegia Type 27, is a rare genetic disorder characterized by slowly progressive weakness and stiffness in the legs. The symptoms of HSP type 27 can vary in severity and onset, but typically include:

• Gradual weakening in the legs [1]
• Urinary bladder disturbance [1][6]
• Spasticity (stiffness) in the legs [4][

Hereditary Spastic Paraplegia (HSP) 27, also known as Autosomal Recessive Spastic Paraplegia type 27, is a rare and complex neurological disorder. Diagnostic tests for HSP 27 are crucial in confirming the diagnosis and ruling out other conditions.

Electrophysiologic studies: These studies can assess peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP (8). This can provide valuable information on the extent of nerve damage and muscle weakness.

Genetic testing: Genetic testing for SPG4/spastin mutations is available commercially and can provide laboratory confirmation of the diagnosis (7). However, it's essential to note that genetic testing may not be necessary or recommended in all cases, especially if the clinical presentation is typical of HSP 27.

Imaging studies: Brain and spine MRI can help identify structural abnormalities associated with HSP 27. These imaging studies can also rule out other conditions that may present with similar symptoms (6).

Clinical evaluation: A thorough clinical evaluation by a neurologist or geneticist is essential in diagnosing HSP 27. This includes assessing the patient's medical and family history, neurological examination, progressive course of the disease, biomarker dosages, and other ancillary testing.

It's worth noting that diagnosis of HSP 27 can be challenging due to its rarity and variable presentation (2). A multidisciplinary approach involving neurologists, geneticists, and other specialists may be necessary for accurate diagnosis and management.

References:

• [6] - Clinical Genetic Test offered by Mayo Clinic Laboratories
• [7] - Genetic testing for SPG4/spastin mutations is available commercially
• [8] - Electrophysiologic studies are useful

Hereditary Spastic Paraplegia (HSP) is a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. While there is no cure for HSP, various treatment options are available to manage its symptoms.

Pharmacological Treatment

Research has identified several pharmacological treatments that may help alleviate symptoms of HSP. These include:

• Botulinum toxin: Studies have shown that botulinum toxin injections can be effective in reducing spasticity and improving mobility in individuals with HSP [4][8].
• Baclofen: Baclofen is a muscle relaxant that has been used to treat spasticity in HSP patients. It works by blocking the action of certain nerve cells, which helps to reduce muscle stiffness [7].
• Tizanidine: Tizanidine is another muscle relaxant that may be prescribed to help manage spasticity in HSP patients.
• Diazepam: Diazepam is a benzodiazepine that can be used to treat muscle spasms and anxiety associated with HSP.

Other Treatments

In addition to pharmacological treatments, other options are available to manage symptoms of HSP. These include:

• Physical therapy: Physical therapy can help improve mobility and reduce spasticity in individuals with HSP.
• Orthoses: Orthoses, such as splints or braces, may be used to support the lower limbs and improve mobility.

It's essential to note that each individual with HSP is unique, and treatment plans should be tailored to their specific needs. A healthcare professional can help determine the most effective treatment plan for a person with HSP.

References:

[4] Oct 16, 2024 — Botulinum toxin was administered to ambulatory persons with HSP, with the treatment goals and targeted muscles differing within the group. [7] Management and treatment. Management is symptomatic with physiotherapy, anti-spasticity drugs (baclofen, tizanidine), and orthoses. [8] Like SPG7, mutations in GBA2 and PNPLA6 can result in either spastic paraplegia or other neurological disorders, which may be treated with botulinum toxin.

Differential Diagnosis of Hereditary Spastic Paraplegia

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. However, differential diagnosis of HSP should also exclude other conditions that present with similar symptoms.

Conditions to Consider in Differential Diagnosis:

• Multiple sclerosis
• Structural abnormalities involving the spinal cord
• B12 deficiency
• Adrenomyeloneuropathy
• Spastic diplegia (which presents with nearly identical day-to-day effects and is treatable with physical therapy)
• Cerebral palsy (early-onset forms of HSP can mimic cerebral palsy)

Key Points to Consider:

• The differential diagnosis includes a broad range of conditions, making it challenging to diagnose HSP accurately.
• Early-onset forms of HSP can be mistaken for cerebral palsy due to similar symptoms.
• Levels of 27-OHC seem to be associated with disease severity in some cases, which can help guide a differential diagnosis.

References:

• [6] 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.
• [8] Differential diagnosis of HSP should also exclude spastic diplegia which presents with nearly identical day-to-day effects and even is treatable with physical therapy.
• [12] Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common “mimics” of cerebral palsy.