hereditary spastic paraplegia 39

Hereditary Spastic Paraplegia 39 (SPG39) is a rare neurodegenerative disorder characterized by progressive weakness and spasticity in the lower limbs [3]. It is an autosomal recessive condition, meaning that it is inherited in a recessive pattern, where a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [1][2].

The primary symptoms of SPG39 include:

• Progressive spasticity and weakness in the lower limbs
• Distal upper and lower extremity wasting
• Motor axonopathy affecting upper and lower limbs

SPG39 is a rare form of hereditary spastic paraplegia, which constitutes a diverse group of neurological disorders typically arising from single-gene defects [14]. The global incidence rate of HSP is 3.6 per 100,000 individuals.

It's worth noting that SPG39 is associated with a motor axonopathy affecting upper and lower limbs and resulting in progressive wasting of distal upper and lower extremity muscles [3].

References:

[1] Rainier et al. (2008) - The form of motor neuron disease designated spastic paraplegia-39 (SPG39) by Rainier et al. (2008) is an autosomal recessive progressive spastic paraplegia associated with distal upper and lower extremity wasting.

[2] OMIM - For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.

[3] SPG39 is associated with a motor axonopathy affecting upper and lower limbs and resulting in progressive wasting of distal upper and lower extremity muscles.

[14] Hereditary spastic paraplegia (HSP) constitutes a diverse group of rare neurological disorders, typically arising from single-gene defects, with a global incidence rate of 3.6 per 100,000 individuals.

Hereditary Spastic Paraplegia (HSP) is a group of rare genetic disorders that affect the nervous system, leading to progressive weakness and stiffness in the legs. The signs and symptoms of HSP can vary depending on the specific subtype, but here are some common manifestations:

• Progressive spasticity: Patients experience increasing muscle stiffness and spasms in the legs, which can lead to difficulty walking or standing.
• Muscle wasting: As the disease progresses, patients may notice wasting of the muscles in their legs, particularly in the distal upper and lower extremities.
• Reduced cognitive functioning: Some forms of HSP can affect cognitive function, leading to difficulties with memory, attention, and decision-making.
• Cerebellar ataxia: Patients may experience problems with balance and coordination due to cerebellar dysfunction.
• Urinary bladder disturbances: Some individuals with HSP may experience urinary incontinence or other bladder control issues.
• Abnormal gait: The disease can cause patients to develop an abnormal gait, characterized by a stiff-legged walk or dragging of the toes when walking.

These symptoms can vary in severity and progression depending on the specific subtype of HSP. In some cases, the disease may be limited to pure spastic paraplegia, with minimal or no other symptoms (see [2][6]). However, in more severe forms, patients may experience a range of additional symptoms, including cognitive decline and ataxia ([1][4]).

It's worth noting that the age of onset can vary significantly, with some individuals experiencing symptoms as early as childhood, while others may not develop symptoms until later in life (see [7]).

Hereditary Spastic Paraplegia (HSP) 39 is a genetically heterogeneous group of neurological conditions characterized by lower-extremity spastic weakness. Diagnostic tests for HSP 39 are crucial in identifying the genetic cause of the condition, which can aid in diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling.

Genetic Testing

Several genetic testing options are available for HSP 39, including:

• Multi-gene panel: This test analyzes multiple genes associated with HSP, including SPAST, ATL1, SPG11, CYP7B1, and others [4]. The Invitae Hereditary Spastic Paraplegia Comprehensive Panel is an example of a multi-gene panel that tests 103 genes, including the most common genetic causes of HSP [4].
• Sequence analysis: This test involves analyzing the entire coding region of specific genes associated with HSP, such as PNPLA6 [11]. Bi-directional Sanger Sequence Analysis offered by Genome Diagnostics Laboratory is an example of this type of testing.
• Non-coding variant assessment: A 75-gene panel that includes assessment of non-coding variants is also available for patients with a clinical suspicion of spastic paraplegia [6].

Other Diagnostic Tests

In addition to genetic testing, other diagnostic tests may be used in the evaluation of HSP 39, including:

• Laboratory tests: Various laboratory tests can aid in diagnosing HSP 39, such as blood tests and urine analysis.
• MRI scans: Magnetic Resonance Imaging (MRI) scans of the brain and spine can reveal cerebellar and/or spinal cord atrophy [8].
• Electrophysiologic studies: These studies are useful for assessing peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP [9].

Clinical Evaluation

A clinical diagnosis of HSP 39 is based on medical and family history, neurological and neuropsychological evaluations, neuropathological studies, other ancillary testing, and exclusion of metabolic disorders [12]. A thorough clinical evaluation by a healthcare professional is essential for accurate diagnosis.

References:

[4] The Invitae Hereditary Spastic Paraplegia Comprehensive Panel analyzes genes associated with hereditary spastic paraplegia (HSP), a clinically and genetically heterogeneous group of neurological conditions characterized by lower-extremity spastic weakness. [6] A 75 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of spastic paraplegia. [8] MRI scans of the brain and spine can reveal cerebellar and/or spinal cord atrophy [8]. [9] Electrophysiologic studies are useful for assessing peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP [9]. [11] Sequence analysis of the entire coding region, Bi-directional Sanger Sequence Analysis offered by Genome Diagnostics Laboratory. [12] Hereditary spastic paraplegia (HSP) comprises a diverse group of neurodegenerative disorders characterized by ... A clinical diagnosis of HSP is based on medical and family history, neurological and neuropsychological evaluations, neuropathological studies, other ancillary testing and exclusion of metabolic ... AR Spastic paraplegia 39.

Medications 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 isn't a cure available, treatment can help manage symptoms. Medications play a crucial role in reducing muscle spasticity and improving mobility.

• Baclofen: A muscle relaxant that helps reduce muscle tone and spasms. It's often prescribed to alleviate lower limb spasticity.
• Tizanidine: Another muscle relaxant used to treat muscle spasms, stiffness, and tightness in the legs.
• Gabapentin/Pregabalin: These medications are sometimes prescribed as muscle relaxants to reduce spasticity and improve mobility.

Other Therapeutic Options

In addition to medications, other therapeutic options may be recommended by healthcare professionals, such as:

• Physical therapy: Regular exercise and physical activity can help maintain mobility, strength, and range of motion.
• Botulinum toxin injections: These injections can help reduce muscle spasms and improve mobility.

Important Notes

It's essential to consult a doctor or pharmacist for personalized advice on medication use and potential side effects. Possible side effects of these medications include drowsiness, dizziness, weakness, confusion, and upset stomach.

References:

• [4] - Hereditary spastic paraplegia 39
• [8] - Oral medications such as Baclofen, Tizanidine, Gabapentin/Pregabalin are prescribed as muscle relaxants to reduce spasticity.
• [10] - Clinical Characteristics and Recommended Treatment: Hereditary Spastic Paraplegia. The predominant signs and symptoms of hereditary spastic paraplegia ... Drugs to reduce muscle spasticity ...
• [11] Possible side effects for these drugs include drowsiness, dizziness, weakness, confusion and upset stomach.

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 [7]. When considering the differential diagnosis for HSP, it's essential to exclude other conditions