hereditary spastic paraplegia 15

Hereditary Spastic Paraplegia (HSP) type 15, also known as Autosomal Recessive Spastic Paraplegia Type 15, is a complex form of HSP characterized by a childhood to adulthood onset of slowly progressive lower limb spasticity [12]. This condition results in gait disturbance, extensor plantar responses, and decreased vibration sense [12].

Spastic paraplegia type 15 is part of a group of genetic disorders known as hereditary spastic paraplegias, which are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia) [2]. This condition typically affects the lower limbs and can cause neurological impairment, including intellectual disability or dementia [3].

The clinical features of HSP type 15 include:

• Lower limb muscle weakness
• Pes cavus
• Macular degeneration
• Nystagmus
• Reduced visual acuity
• Retinal degeneration
• Visual impairment [5]

Spastic paraplegia-15 (SPG15) is an autosomal recessive neurodegenerative disorder characterized by progressive spasticity primarily affecting the lower limbs [6]. The condition typically begins in mid-to-late childhood or adolescence, with symptoms gradually worsening over time [4].

In addition to lower limb involvement, HSP type 15 can also affect other organ systems, leading to a range of manifestations resulting from central and peripheral nervous system dysfunction [10]. These may include abnormalities of the brain, cerebellar ataxia, and peripheral neuropathy.

Overall, hereditary spastic paraplegia type 15 is a complex condition that requires careful diagnosis and management. Early recognition and intervention can help improve outcomes for individuals affected by this disorder.

Hereditary Spastic Paraplegia (HSP) type 15 is a rare genetic disorder that affects the nervous system, causing progressive muscle weakness and stiffness in the legs. The signs and symptoms of HSP type 15 can vary from person to person, but here are some common ones:

• Slowly progressive muscle stiffness (spasticity): This is one of the hallmark symptoms of HSP type 15, where muscles in the legs become stiff and rigid, leading to difficulty walking or moving.
• Paralysis (paraplegia): As the condition progresses, people with HSP type 15 may experience partial or complete paralysis of the lower limbs.
• Muscle weakness: Muscle weakness is another common symptom, which can range from mild to severe.
• Intellectual disability: Unfortunately, most people with HSP type 15 experience a decline in intellectual ability over time.

It's essential to note that the symptoms of HSP type 15 can be quite variable, and some individuals may not exhibit all of these signs. The progression of the condition can also differ from person to person.

References:

• [1] Apr 1, 2014 — Most people with spastic paraplegia type 15 experience a decline in intellectual ability and an increase in muscle weakness and nerve ...
• [6] Signs and symptoms​​ Hereditary spastic paraplegia (HSP) type 15 is characterised by slowly progressive muscle stiffness (spasticity) and paralysis (paraplegia) ...
• [9] Symptoms include slowly progressive lower limb spasticity, gait disturbance, extensor plantar responses, decreased vibration sense, mild intellectual disability ...

Hereditary Spastic Paraplegia 15 (SPG15) can be diagnosed through various genetic tests that analyze the ZFYVE26 gene, which is responsible for causing this condition.

• Sequence analysis: This test involves analyzing the entire coding region of the ZFYVE26 gene to identify any mutations or variations that may be associated with SPG15. [11]
• Bi-directional Sanger Sequence Analysis: This is a type of sequence analysis that provides more detailed information about the genetic changes in the ZFYVE26 gene. It is offered by Genome Diagnostics Laboratory and can help confirm a diagnosis of SPG15. [11]

It's worth noting that these tests are typically performed on a proband (an individual with symptoms) who has suggestive findings, and biallelic pathogenic variants in ZFYVE26 must be identified to establish a diagnosis of SPG15. [5]

Additionally, there are other genetic panels available that can help diagnose SPG15, such as the Invitae Hereditary Spastic Paraplegia Comprehensive Panel, which analyzes 103 genes associated with HSP, including the most common genetic causes of SPG15. [1]

Hereditary Spastic Paraplegia 15 (SPG15) is a rare genetic disorder that affects the nervous system, leading to progressive muscle weakness and spasticity in the lower limbs. While there is no specific treatment for SPG15, various drug therapies may help manage its symptoms.

Antispasmodic drugs: These medications can help reduce

Hereditary Spastic Paraplegia 15 (SPG15) is a complex genetic disorder that can be challenging to diagnose due to its diverse range of symptoms and manifestations. When considering the differential diagnosis for SPG15, several conditions should be taken into account.

• Multiple Sclerosis: This autoimmune disease can present with similar symptoms to SPG15, including difficulty walking, muscle weakness, and visual disturbances [9].
• Structural Abnormalities of the Spinal Cord: Conditions such as syringomyelia or tethered cord syndrome can cause progressive spasticity and weakness in the lower limbs, mimicking the symptoms of SPG15 [9].
• B12 Deficiency: Vitamin B12 deficiency can lead to neurological symptoms, including difficulty walking, muscle weakness, and visual disturbances, which may be mistaken for SPG15 [9].
• Adrenomyeloneuropathy: This rare genetic disorder affects the adrenal glands and nervous system, causing progressive spasticity and weakness in the lower limbs, similar to SPG15 [9].

In addition to these conditions, other factors should also be considered when differentiating SPG15 from other genetic diseases associated with spasticity. These include:

• Imaging Abnormalities: Magnetic Resonance Imaging (MRI) can help identify structural abnormalities in the brain and spinal cord that may be associated with SPG15 [15].
• Genetic Testing: Genetic testing can confirm the diagnosis of SPG15 by identifying mutations in the KIAA1731 gene [11].

It's essential to note that a comprehensive diagnostic evaluation, including clinical assessment, imaging studies, and genetic testing, is necessary to accurately diagnose SPG15 and rule out other potential causes of spasticity.

References:

[9] The differential diagnosis includes multiple sclerosis, structural abnormalities involving the spinal cord, B12 deficiency, adrenomyeloneuropathy and other ...

[11] The predominant signs and symptoms of hereditary spastic paraplegia (HSP) ... accounting for approximately 10%-15% of all autosomal dominant HSP. SPG3A is the main cause of autosomal dominant HSP with early onset (occurs in >75% of individuals in this category). ... 3. Differential Diagnosis of Hereditary Spastic Paraplegia.

[15] 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. ... [15 –18] SPG11 (OMIM #604360) SPG15 (OMIM #270700) SPG48 (OMIM #613647) ... While these findings are not specific, they can help guide a differential diagnosis. The ...