Materiały źródłowe

• #1 Hereditary Spastic Paraplegia | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/hereditary-spastic-paraplegia

  Healthcare providers use several methods to diagnose hereditary spastic paraplegia (HSP). Theyll take a family and medical history to learn about the persons symptoms and whether family members have similar issues. […] Doctors can diagnose HSP if genetic testing identifies a related gene mutation and the symptoms align with the condition. […] The healthcare provider may also order genetic testing that looks for changes in specific genes linked to HSP. This testing can confirm an HSP diagnosis and identify the type. […] In some cases, doctors may order imaging tests such as an MRI (magnetic resonance imaging, to check for brain or spinal cord issues that may explain the symptoms. […] Blood tests, nerve conduction studies, or lumbar punctures can rule out other conditions with similar symptoms.

• #1 Hereditary Spastic Paraplegia | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia (HSP) refers to a group of over 80 different genetic conditions that present with progressive spasticity (muscle tightness) and weakness. […] The diagnosis of HSP is based on a neurological examination and other tests: Typical symptoms (spastic and weakness of the legs) […] A number of specialized tests may be used in the diagnostic evaluation for HSP, including laboratory tests, genetic testing, MRI scans of the brain and spine, EEG, and nerve conduction tests or an EMG. […] Genetic testing is often able to identify a causative gene mutation. […] The diagnosis of HSP is based on a neurological examination and other tests:

• #1 Hereditary Spastic Paraplegia – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/spinal-cord-disorders/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia is a group of rare hereditary disorders characterized by progressive, spinal, nonsegmental spastic leg paresis, sometimes with intellectual disability, seizures, and other extraspinal deficits. Diagnosis is clinical and sometimes by genetic testing. […] Diagnosis of hereditary spastic paraplegia is by exclusion of other causes and sometimes (eg, if the cause is unclear) by genetic testing. Consultation with a genetic counselor is recommended. […] Suspect hereditary spastic paraplegia in patients with a family history and signs of spastic paraplegia; exclude other causes and if the diagnosis is unclear, consider genetic testing.

• #1 Orphanet: Hereditary spastic paraplegia

  https://www.orpha.net/en/disease/detail/685

  A genetically and clinically heterogeneous group of slowly progressive neurological disorders which in the pure form is characterized by pyramidal signs (weakness, spasticity, brisk tendon reflexes, and extensor plantar responses) predominantly affecting the lower limbs and with possible association of sphincter disturbances and deep sensory loss; and in the complex form by the addition of variable neurological or non-neurological features. […] Diagnosis is based on the clinical symptoms, neurological examination, progressive course of the disease, biomarker dosages, brain and spine MRI, family history, molecular genetic testing, and exclusion of the differential diagnoses. […] Genetic testing is possible where a mutation has previously been identified in a family. […] Differential diagnosis includes multiple sclerosis, spinal vascular abnormality, vitamin B12 deficiency, HTLVI infection, primary lateral sclerosis, diplegic cerebral palsy, metabolic genetic diseases (dopa-responsive dystonia, leukodystrophies, brain metal accumulation disorders).

• #1 Hereditary spastic paraplegia | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/hereditary-spastic-paraplegia?lang=us

  Hereditary spastic paraplegia (HSP) refers to a heterogeneous group of neurodegenerative conditions characterized by progressive degeneration of the corticospinal tracts and posterior column of the spinal cord. […] In its pure phenotype, patients tend to have progressive and symmetric lower limb upper motor neuron signs, including weakness, spasticity, and hyperreflexia. […] However, many patients also have atypical features such as sensory signs, intellectual disability or dementia, or ataxia. […] There are in excess of 70 types, with the most common types carrying an autosomal dominant pattern of inheritance. […] However, up to 40% of cases may be sporadic. […] Often non-specific and variable depending on the underlying genetic type, but features can include corpus callosum atrophy, increased T2 signal intensity in the posterior limb of the internal capsule, spinal cord atrophy, ears of the lynx sign, hypointense T2 signal of the globi pallidi, hydrocephalus, and cerebellar atrophy.

• #1 Hereditary Spastic Paraplegia: What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia is a genetic condition that causes weakness and muscle tightness in your legs. […] A healthcare provider will perform a physical exam, neurological exam and testing to diagnose hereditary spastic paraplegia. […] If your provider suspects hereditary spastic paraplegia, they may suggest tests including: Electromyography, Genetic testing, Magnetic resonance imaging (MRI), Spinal tap (lumbar puncture). […] It can take some time to receive an accurate diagnosis in some cases. Hereditary spastic paraplegia symptoms can look very similar to other conditions like cerebral palsy, multiple sclerosis, Pelizaeus-Merzbacher disease, spinal stenosis. […] There isnt a cure available for hereditary spastic paraplegia, but treatment can help you manage symptoms, which may include medications, physical therapy, occupational therapy, medical shoe inserts, mobility devices.

• #1 Hereditary Spastic Paraplegia Differential Diagnoses

  https://emedicine.medscape.com/article/306713-differential

  Failure to rule out reversible forms of spinal cord lesions (mechanical cord compression or spinal cord tumor) when considering a diagnosis of hereditary spastic paraplegia (HSP) invites problems. […] Conditions to consider in the differential diagnosis of HSP include the following: Hereditary motor-sensory neuropathy type 5, Spondylosis, Atlantoaxial canal stenosis, Arteriovenous malformation compressing spinal cord, Arnold-Chiari syndrome, Tethered cord, Neoplasm, Granuloma, Spinocerebellar ataxias, Adrenomyeloneuropathy, Deficiency of vitamins B-12 and E, Abetalipoproteinemia, Mitochondrial disorders, Human T-cell lymphocytotrophic virus infection, Toxins, Stiff-limb syndrome. […] Differential Diagnoses: Dopamine-Responsive Dystonia, Hydrocephalus, Krabbe Disease, Metachromatic Leukodystrophy, Rapid HIV Testing, Syphilis, Syringomyelia.

• #1 Hereditary Spastic Paraplegia | American Journal of Neuroradiology

  https://www.ajnr.org/ajnr-case-collections-diagnosis/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia (HSP) is a heterogeneous group of familial neurodegenerative disorders characterized by degeneration of the corticospinal tracts and posterior column of the spinal cord with progressive lower limb spasticity. […] MRI helps in early diagnosis and to exclude secondary causes of spastic paraplegia. MRI of the neuraxis may appear normal in HSP. However, MR imaging findings are nonspecific and variable. […] The symmetric periventricular white matter lesions adjacent to the frontal horn of the lateral ventricles give a flame or „ears of the lynx” appearance on axial FLAIR images. The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history. […] MRS may reveal reduced concentrations of NAA, Cr, and Cho and elevated levels of myoinositol. […] DTI often shows increased mean diffusivity and reduced fractional anisotropy in the corpus callosum and periventricular white matter, compatible with damaged myelinated axons.

• #1 Hereditary Spastic Paraplegia: Practice Essentials, Etiology, Epidemiology

  https://emedicine.medscape.com/article/306713-overview

  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, which is the causation of progressive and generally severe lower extremity weakness and spasticity. […] Genetic testing for SPG4/spastin mutations is available commercially, can provide laboratory confirmation of the diagnosis, and can be applied to prenatal testing. […] Electrophysiologic studies are useful for assessing peripheral nerve, muscle, dorsal column, and corticospinal tract involvement in patients with HSP. […] Magnetic resonance imaging (MRI) scans may demonstrate atrophy of the spinal cords and occasionally of the cerebral cortex. […] Currently, no specific treatment exists to prevent, retard, or reverse progressive disability in patients with HSP. Nonetheless, treatment approaches used for chronic paraplegia from other causes are useful.

• #1 Hereditary spastic paraplegia – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/hereditary-spastic-paraplegia/

  The diagnosis of HSP is based on a positive family history, characteristic clinical features, and the exclusion of other neurological conditions. […] MRI of the brain and spinal cord: mild atrophy of the cervical and thoracic spinal cord in pure HSP. […] Nerve conduction studies and electromyography: may be normal or show mild motor neuropathy. […] Motor evoked potentials: decreased or absent in bilateral lower limbs (based on severity of paralysis). […] Molecular genetic testing: to differentiate HSP from other inherited ataxias (spinocerebellar ataxia or Friedreich ataxia). […] Vitamin B12 levels should be checked; HIV and syphilis testing should also be performed to rule out these conditions. […] Lumbar puncture and CSF analysis are usually normal.

• #1 Invitae Hereditary Spastic Paraplegia Comprehensive Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-03251

  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. […] Given that HSPs are a heterogeneous group of conditions, identification of the underlying genetic cause can help confirm a clinical diagnosis, predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials. […] Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS). […] Based on validation study results, this assay achieves 99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions 15bp in length, and exon-level deletions and duplications.

• #1

  https://link.springer.com/article/10.1007/s11910-021-01099-x

  Genetic testing is often performed with gene panels that are tailored to a specific disease category, and therefore an accurate clinical classification becomes a critical step able to significantly influence the diagnostic yield. […] It is critical to remember that CNVs (e.g. exonic deletions in SPAST) are important to consider and may require a separate test (e.g. multiplex ligation probe amplification or MLPA), unless using a method that provides reliable detection such as WGS. […] There are several options for reaching a genetic diagnosis in individuals with HSP and it can be challenging for the clinician to decide upon which approach to adopt. […] A genetic diagnosis rarely leads to findings with direct management implications. However, it may hold future value in that it could be used to enrol patients in clinical trials that target the disease mechanism.

• #1

  https://link.springer.com/article/10.1007/s11910-021-01099-x

  The genetic diagnosis of HSP is complex and can represent a major challenge for clinicians. […] An understanding of the genetic and phenotypic complexity underlying HSP is essential to guide genetic testing strategies. […] Next-generation sequencing has greatly improved our ability to detect a genetic diagnosis in HSP. Yet, large studies have shown that the diagnostic rate for HSP is still only about 45-50% of cases. […] The genetic diagnosis of HSP still represents a great challenge for clinicians, and there are no clear guidelines available about which approach to choose.

• #1

  https://link.springer.com/article/10.1007/s11910-021-01099-x

  Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis. […] In this review, we discuss current challenges to reach a genetic diagnosis in HSP. These include (i) the large number of genes involved and the rapid rate of gene discovery, (ii) major phenotypic overlap between HSP and other disorders and (iii) disorders that mimic HSP. […] An accurate, timely genetic diagnosis in HSP may become particularly relevant as new, targeted therapies are on the horizon. […] There are many genes causative of HSP resulting in a high level of genetic heterogeneity. […] Currently, the Online Mendelian Inheritance in Man (OMIM) lists 81 distinct genetic forms of HSP. […] Due to the rapid rate of progress of HSP research, new genes are being identified on a regular basis.

• #1 Hereditary Spastic Paraplegia Comprehensive Panel Test – PreventionGenetics

  https://www.preventiongenetics.com/testInfo?val=Hereditary-Spastic-Paraplegia-Comprehensive-Panel

  Individuals with symptoms consistent with spastic paraplegia are candidates for this test. […] Because this panel covers genes with dominant, recessive, and X-linked inheritance patterns, this test may be particularly helpful if the inheritance pattern is unclear based on the patients family history. […] Advantages of genetic testing for HSP include confirmation of diagnosis, identification of other health risks associated with complicated HSP, allowing for targeted testing of other family members, and assistance with reproductive planning. […] This multi-gene panel analyzes 103 genes, including the most common genetic causes of Hereditary Spastic Paraplegia (HSP), such as SPAST, ATL1, SPG11, CYP7B1, KIF5A, REEP1, PGN, ZFYVE26 and L1CAM. […] To increase the clinical sensitivity of the test, we also include genes identified more recently; however, each of these genes accounts for a small proportion of individuals with spastic paraplegia.

• #1 SciELO Brazil – Clinical features and management of hereditary spastic paraplegia Clinical features and management of hereditary spastic paraplegia

  https://www.scielo.br/j/anp/a/T7KKdbXLLnppT3RqhgN4GKg/

  Hereditary spastic paraplegia (HSP) is a group of genetically-determined disorders characterized by progressive spasticity and weakness of lower limbs. […] To date, there are up to 60 genetic subtypes described. […] HSP is clinically divided into pure and complicated forms. […] Diagnosis of HSP is based upon individual and family-history as well as clinical and neurological findings such as spastic weakness, hyperreflexia and extensor plantar responses. […] The absence of family history should not eliminate the diagnosis of HSP. […] HSP is characterized by normal motor development followed by slowly progressive spasticity and weakness of the lower limbs. […] In the clinical setting of AD-HSP, screening for mutations in SPG4 is the first step, followed by SPG3a in negative cases. […] Molecular investigation for AR-HSP should be guided by the complicating features. […] Due to its phenotypic variability, the differentiation between various forms of HSP can be difficult on clinical grounds.

• #1 Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4503825/

  The hereditary spastic paraplegias (HSPs) are a group of genetic conditions in which spastic paralysis of the legs is the principal clinical feature. […] In this review, we will then discuss appropriate investigation strategies for HSPs, suggesting how these might evolve with the introduction of next-generation sequencing technology. […] The traditional approach to investigating a patient with possible HSP is to define the phenotype and inheritance pattern, exclude alternative causes, then attempt to make a definitive molecular genetic diagnosis, where possible using clinical and family history information to focus genetic investigations appropriately. […] For those individuals in whom the above baseline investigations are unremarkable and/or where the family history and clinical features point towards a specific genetic diagnosis, it is then appropriate to test for the suspected mutation.

• #1

  https://link.springer.com/article/10.1007/s00415-014-7598-y

  For those individuals in whom the above baseline investigations are unremarkable and/or where the family history and clinical features point towards a specific genetic diagnosis, it is then appropriate to test for the suspected mutation. […] There is considerable clinical utility for HSP families in detecting their causative mutation. It gives diagnostic certainty, prevents further unnecessary investigations and opens the possibility of predictive and prenatal testing. […] However, until very recently, in many healthcare systems, economic factors necessitated that genetic investigations were restricted to analysis of HSP genes in which there was the highest chance of detecting a mutation, as the expense of analysing rarely-causative genes was not justified by the low mutation detection rate per additional gene analysed.

• #1 Hereditary Spastic Paraplegia – Brain, Spinal Cord, and Nerve Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/spinal-cord-disorders/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia is diagnosed by excluding other disorders that cause similar symptoms (such as multiple sclerosis and spinal cord compression) and by determining whether other family members have hereditary spastic paraplegia. […] Blood tests to check for the genes that cause the disorder (genetic testing) are sometimes done. […] Consultation with a genetic counselor is recommended.

• #1 What is the diagnosis of Hereditary Spastic Paraplegia? | OnlyMyHealth

  https://www.onlymyhealth.com/what-diagnosis-hereditary-spastic-paraplegia-12977606077

  The diagnosis of Hereditary Spastic Paraplegia is primarily done by neurological examination and testing to rule out other disorders. Family history may also be taken to come to a accurate decision. […] Hereditary spastic paraplegias are diagnosed by the following ways: The doctor starts with the analyses of some typical symptoms of this disease, weakness and neurological findings of lower extremity spasticity. Family history; often times, if someone in the family such as a first-degree relative is affected by this disease, the patient is likely to have a greater risk of developing it. The exclusion of other disorders. […] Genetic testing has been becoming increasingly available and especially useful in the clinical diagnosis of HSP. Considering that molecular genetic testing currently does not include all the genes known to lead to HSP, an absence of the identified mutation in a gene that is known to cause HSP does not really exclude the diagnosis of HSP. […] Genetic counseling depends on an accurate diagnosis as well as determination of the mode of inheritance in every family. It may help in the determination of HSPs genetic type.

• #1 HSP : HSP & PLS : Spastic Paraplegia Foundation

  https://sp-foundation.org/understanding-pls-hsp/hsp.html

  What is the risk of getting HSP? There are some seventy different forms of HSP, with three different modes of inheritance: autosomal dominant, autosomal recessive and X-linked. Each mode has a different risk factor, which ranges from almost none to 50%. […] What other conditions cause spastic paraplegia and weakness of muscles? Muscle spasticity and weakness can also be caused by other conditions including (but not limited to) Tropical Spastic Paraparesis and conditions called Lathyrism and Konzo caused by toxins in the plants lathyrus sativus and cassava that also cause muscle spasticity and weakness.

• #1 Is Hereditary Spastic Paraplegia a Disability? Not to This Girl.

  https://www.brainandlife.org/articles/a-six-year-old-with-hereditary-spastic-paraplegia-keeps-moving

  „Years ago, only specialized centers could do the gene testing, but now [more sophisticated and faster methods] for gene analysis can be obtained commercially from different companies,” Dr. Blackstone says. […] HSP is a genetically complex disorder. „More than 70 different genesand the number is risingcause HSP, and this is more than almost any disease. We couldn’t test for many forms of HSP and similar diseases even five or 10 years ago, since the affected genes were not yet known,” Dr. Blackstone says. […] The fact that genetic diseases can now be identified so early in life affords the advantage of precious time. „Many patients develop symptoms in their late teens or 20s and 30s, and genetic tools can tell us who is at risk early on,” Dr. Fink says. „We want to understand HSP at its fundamental level and to develop interventions that can prevent the appearance and progression of symptoms.”

• #1

  https://journals.lww.com/annalsofian/fulltext/2019/22030/clinico_investigative_profile_of_hereditary.22.aspx

  Hereditary spastic paraplegia (HSP) is a group of neurogenetic disorders seen mainly in adults. With the advancement in genetics, more than 78 types of HSP have been identified, with increasing identification of HSP in children. […] A total of 11 patients had a diagnosis of HSP (genetically confirmed), with mean age of presentation at 21.7 months. […] The mean delay in diagnosis was 5.2 years after initial presentation. […] HSP is probably not uncommon. Recessive form of HSP is more frequently seen in children. Because of lack of awareness, there is delay in reaching the final diagnosis. […] Diagnosis of HSP in pediatric cases can be difficult in the absence of a positive family history. […] The nonprogress or very slow progression of the disease also justifies the diagnosis of cerebral palsy in many children.

• #1 Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq) | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT05354622/hereditary-spastic-paraplegia-genomic-sequencing-initiative-hspseq

  The purpose of the HSP Sequencing Initiative is to better understand the role of genetics in hereditary spastic paraplegia (HSP) and related disorders. […] In childhood-onset forms, initial symptoms are often non-specific and many children may not receive a diagnosis until progressive features are recognized, often leading to a significant diagnostic delay. Genetic testing in children with spastic paraplegia is not yet standard practice. […] The clinical diagnosis of HSP does not suggest anything about its molecular cause, with a wide range of outcomes dependent on the gene affected. […] The aims of this study include: To identify genetic findings (single nucleotide changes or copy number variants) in patients with progressive spastic paraplegia and related disorders. […] To correlate molecular findings with HSP phenotypes.

• #1 Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4503825/

  There is considerable clinical utility for HSP families in detecting their causative mutation. It gives diagnostic certainty, prevents further unnecessary investigations and opens the possibility of predictive and prenatal testing. […] However, this has changed with the introduction of next-generation sequencing, which allows cost-effective analysis of many genes together, using approaches including (1) sequencing of large panels of genes, (2) sequencing of all coding exons in the genome, or (3) sequencing of entire genomes. […] Although these developments are undeniably positive, there are pitfalls and caveats associated with next-generation sequencing approaches. […] Finally, while next-generation sequencing approaches have the potential to increase rates of molecular genetic diagnosis in HSP, they do not remove the need for careful phenotypingthis is still important, as it can help to focus bioinformatics analysis onto the most relevant genes.

• #1

  https://link.springer.com/article/10.1007/s00415-014-7598-y

  Although these developments are undeniably positive, there are pitfalls and caveats associated with next-generation sequencing approaches. […] Finally, while next-generation sequencing approaches have the potential to increase rates of molecular genetic diagnosis in HSP, they do not remove the need for careful phenotypingthis is still important, as it can help to focus bioinformatics analysis onto the most relevant genes.

• #1

  https://link.springer.com/article/10.1007/s11910-021-01099-x

  The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP. […] There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments.

• #1 Childhood Onset HSP | HSP Support Group

  https://hspgroup.org/childhood-onset-hsp/

  While hereditary spastic paraplegia (HSP) is more broadly known as an adult-onset rare neurological condition, it also affects children. […] The diagnosis of HSP in children in the UK usually begins with a comprehensive medical evaluation and neurological exam by a specialist, such as a neurologist or a geneticist. The doctor will review the child’s medical history, perform a physical examination, and assess the child’s motor skills, muscle tone, reflexes, and coordination. […] In general, genetic testing is required to confirm the diagnosis and identify the specific genetic mutation that is causing the disease. This may involve a blood or saliva test to analyse the child’s DNA. […] It’s important to note that the diagnostic process for HSP can be complex and may involve multiple tests and evaluations over time. A definitive diagnosis may take several months or even years to confirm, and may involve consultation with multiple medical specialists.

• #1 Is Hereditary Spastic Paraplegia a Disability? Not to This Girl.

  https://www.brainandlife.org/articles/a-six-year-old-with-hereditary-spastic-paraplegia-keeps-moving

  „Knowing about genetic disease from the time a person is born gives us the ability to intervene and alter disease progress before significant disability develops,” Dr. Blackstone adds. […] At present, the underlying nerve degeneration in HSP cannot be prevented, stopped, or reversed, but there are treatments that can alleviate the symptoms. […] Children with HSP require a different approach and treatment than adults because of their ongoing growth and development, says Mauricio Delgado, MD, FAAN, director of neurology at Texas Scottish Rite Hospital for Children and a professor of neurology at the University of Texas Southwestern Medical Center in Dallas. […] „Symptomatic therapies [that treat the symptoms but not the cause of the disease] do have some benefit, but they don’t result in dramatic improvement from the current medications,” says Dr. Blackstone.

• #2 Hereditary Spastic Paraplegia: What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia is a genetic condition that causes weakness and muscle tightness in your legs. […] A healthcare provider will perform a physical exam, neurological exam and testing to diagnose hereditary spastic paraplegia. […] If your provider suspects hereditary spastic paraplegia, they may suggest tests including: Electromyography, Genetic testing, Magnetic resonance imaging (MRI), Spinal tap (lumbar puncture). […] It can take some time to receive an accurate diagnosis in some cases. Hereditary spastic paraplegia symptoms can look very similar to other conditions like cerebral palsy, multiple sclerosis, Pelizaeus-Merzbacher disease, spinal stenosis. […] There isnt a cure available for hereditary spastic paraplegia, but treatment can help you manage symptoms, which may include medications, physical therapy, occupational therapy, medical shoe inserts, mobility devices.

• #2 Orphanet: Hereditary spastic paraplegia

  https://www.orpha.net/en/disease/detail/685

  A genetically and clinically heterogeneous group of slowly progressive neurological disorders which in the pure form is characterized by pyramidal signs (weakness, spasticity, brisk tendon reflexes, and extensor plantar responses) predominantly affecting the lower limbs and with possible association of sphincter disturbances and deep sensory loss; and in the complex form by the addition of variable neurological or non-neurological features. […] Diagnosis is based on the clinical symptoms, neurological examination, progressive course of the disease, biomarker dosages, brain and spine MRI, family history, molecular genetic testing, and exclusion of the differential diagnoses. […] Genetic testing is possible where a mutation has previously been identified in a family. […] Differential diagnosis includes multiple sclerosis, spinal vascular abnormality, vitamin B12 deficiency, HTLVI infection, primary lateral sclerosis, diplegic cerebral palsy, metabolic genetic diseases (dopa-responsive dystonia, leukodystrophies, brain metal accumulation disorders).

• #2 A Hundred Faces for a Unique Disorder: Hereditary Spastic Paraplegia

  https://www.imrpress.com/journal/JIN/23/6/10.31083/j.jin2306115/htm

  Hereditary Spastic Paraplegia (HSP), also known as Hereditary Spastic Paraparesis, Familial Spastic Paraplegia, and Strumpell-Lorrain syndrome, refers to a group of inherited neurodegenerative disorders characterized by lesions of the pyramidal tract. The disorder manifests with progressive lower limb spasticity and weakness, and exhibits wide clinical and genetic variability. […] Early diagnosis of HSP is based on the presence of gradually progressive weakness and stiffness in the lower limbs, a positive family history of a similar disorder, exclusion of other possible neurological diseases, and genetic analysis. Electrophysiological examinations, and brain and spinal MRIs may be useful in the differential diagnosis of other neurological disorders but they are not specific for diagnosing HSP.

• #2 Hereditary spastic paraplegia – UpToDate

  https://www.uptodate.com/contents/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia (HSP) refers to a group of familial diseases that are characterized by progressive degeneration of the corticospinal tracts. Clinically, they present with lower limb spasticity and weakness. […] The genetic classification of HSP is based upon mode of inheritance, chromosomal locus, and causative mutation (if known). Hereditary spastic paraplegias include autosomal dominant, autosomal recessive, and X-linked forms. […] The correlation of clinical classification (pure or complicated) with genetic classification (SPG type) is imperfect, and some genetic types of HSP are associated with both pure and complicated phenotypes.

• #2

  https://journals.lww.com/annalsofian/fulltext/2019/22030/clinico_investigative_profile_of_hereditary.22.aspx

  HSP can be transmitted in an AD, AR, or X-linked (XL) manner. […] To conclude, this study confirms the genetic and clinical heterogeneity of childhood-onset HSP. The absence of positive family history should not deter a clinician from considering HSP when more obvious etiologies have been excluded. Genetic studies using next generation sequencing techniques are very helpful in reaching the diagnosis. Pediatric HSP patients can present with delayed walking or variable gait difficulties even in toddlerhood. Investigating asymptomatic first-degree relatives would be sensible in both suspected and definitively diagnosed cases of HSP.

• #2 Hereditary spastic paraplegia

  https://www.nhs.uk/conditions/hereditary-spastic-paraplegia/

  Hereditary spastic paraplegia is diagnosed after a thorough clinical examination and the identification of typical symptoms. […] Other conditions that cause mobility problems and muscle stiffness and weakness, such as multiple sclerosis and cerebral palsy, need to be ruled out first. […] A number of specialised tests may be used during diagnosis, including MRI scans of the brain and spine and cerebrospinal fluid analysis. […] In some cases, genetic testing may also be needed.

• #2 Hereditary spastic paraplegia | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/hereditary-spastic-paraplegia?lang=us

  Hereditary spastic paraplegia (HSP) refers to a heterogeneous group of neurodegenerative conditions characterized by progressive degeneration of the corticospinal tracts and posterior column of the spinal cord. […] In its pure phenotype, patients tend to have progressive and symmetric lower limb upper motor neuron signs, including weakness, spasticity, and hyperreflexia. […] However, many patients also have atypical features such as sensory signs, intellectual disability or dementia, or ataxia. […] There are in excess of 70 types, with the most common types carrying an autosomal dominant pattern of inheritance. […] However, up to 40% of cases may be sporadic. […] Often non-specific and variable depending on the underlying genetic type, but features can include corpus callosum atrophy, increased T2 signal intensity in the posterior limb of the internal capsule, spinal cord atrophy, ears of the lynx sign, hypointense T2 signal of the globi pallidi, hydrocephalus, and cerebellar atrophy.

• #2 Hereditary Spastic Paraplegia | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/hereditary-spastic-paraplegia

  Healthcare providers use several methods to diagnose hereditary spastic paraplegia (HSP). Theyll take a family and medical history to learn about the persons symptoms and whether family members have similar issues. […] Doctors can diagnose HSP if genetic testing identifies a related gene mutation and the symptoms align with the condition. […] The healthcare provider may also order genetic testing that looks for changes in specific genes linked to HSP. This testing can confirm an HSP diagnosis and identify the type. […] In some cases, doctors may order imaging tests such as an MRI (magnetic resonance imaging, to check for brain or spinal cord issues that may explain the symptoms. […] Blood tests, nerve conduction studies, or lumbar punctures can rule out other conditions with similar symptoms.

• #2 Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next-generation sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4503825/

  There is considerable clinical utility for HSP families in detecting their causative mutation. It gives diagnostic certainty, prevents further unnecessary investigations and opens the possibility of predictive and prenatal testing. […] However, this has changed with the introduction of next-generation sequencing, which allows cost-effective analysis of many genes together, using approaches including (1) sequencing of large panels of genes, (2) sequencing of all coding exons in the genome, or (3) sequencing of entire genomes. […] Although these developments are undeniably positive, there are pitfalls and caveats associated with next-generation sequencing approaches. […] Finally, while next-generation sequencing approaches have the potential to increase rates of molecular genetic diagnosis in HSP, they do not remove the need for careful phenotypingthis is still important, as it can help to focus bioinformatics analysis onto the most relevant genes.

• #2

  https://link.springer.com/article/10.1007/s11910-021-01099-x

  Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis. […] In this review, we discuss current challenges to reach a genetic diagnosis in HSP. These include (i) the large number of genes involved and the rapid rate of gene discovery, (ii) major phenotypic overlap between HSP and other disorders and (iii) disorders that mimic HSP. […] An accurate, timely genetic diagnosis in HSP may become particularly relevant as new, targeted therapies are on the horizon. […] There are many genes causative of HSP resulting in a high level of genetic heterogeneity. […] Currently, the Online Mendelian Inheritance in Man (OMIM) lists 81 distinct genetic forms of HSP. […] Due to the rapid rate of progress of HSP research, new genes are being identified on a regular basis.

• #2

  https://link.springer.com/article/10.1007/s11910-021-01099-x

  Genetic testing is often performed with gene panels that are tailored to a specific disease category, and therefore an accurate clinical classification becomes a critical step able to significantly influence the diagnostic yield. […] It is critical to remember that CNVs (e.g. exonic deletions in SPAST) are important to consider and may require a separate test (e.g. multiplex ligation probe amplification or MLPA), unless using a method that provides reliable detection such as WGS. […] There are several options for reaching a genetic diagnosis in individuals with HSP and it can be challenging for the clinician to decide upon which approach to adopt. […] A genetic diagnosis rarely leads to findings with direct management implications. However, it may hold future value in that it could be used to enrol patients in clinical trials that target the disease mechanism.

• #2

  https://link.springer.com/article/10.1007/s00415-014-7598-y

  The hereditary spastic paraplegias (HSPs) are a group of genetic conditions in which spastic paralysis of the legs is the principal clinical feature. […] In this review, we will provide a brief overview of the classification, clinical features and genetics of HSP, highlighting selected HSP subtypes that are of particular clinical interest. We will then discuss appropriate investigation strategies for HSPs, suggesting how these might evolve with the introduction of next-generation sequencing technology. […] The traditional approach to investigating a patient with possible HSP is to define the phenotype and inheritance pattern, exclude alternative causes, then attempt to make a definitive molecular genetic diagnosis, where possible using clinical and family history information to focus genetic investigations appropriately.

• #2 Hereditary Spastic Paraplegia – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/spinal-cord-disorders/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia is a group of rare hereditary disorders characterized by progressive, spinal, nonsegmental spastic leg paresis, sometimes with intellectual disability, seizures, and other extraspinal deficits. Diagnosis is clinical and sometimes by genetic testing. […] Diagnosis of hereditary spastic paraplegia is by exclusion of other causes and sometimes (eg, if the cause is unclear) by genetic testing. Consultation with a genetic counselor is recommended. […] Suspect hereditary spastic paraplegia in patients with a family history and signs of spastic paraplegia; exclude other causes and if the diagnosis is unclear, consider genetic testing.

• #2 Is Hereditary Spastic Paraplegia a Disability? Not to This Girl.

  https://www.brainandlife.org/articles/a-six-year-old-with-hereditary-spastic-paraplegia-keeps-moving

  „Knowing about genetic disease from the time a person is born gives us the ability to intervene and alter disease progress before significant disability develops,” Dr. Blackstone adds. […] At present, the underlying nerve degeneration in HSP cannot be prevented, stopped, or reversed, but there are treatments that can alleviate the symptoms. […] Children with HSP require a different approach and treatment than adults because of their ongoing growth and development, says Mauricio Delgado, MD, FAAN, director of neurology at Texas Scottish Rite Hospital for Children and a professor of neurology at the University of Texas Southwestern Medical Center in Dallas. […] „Symptomatic therapies [that treat the symptoms but not the cause of the disease] do have some benefit, but they don’t result in dramatic improvement from the current medications,” says Dr. Blackstone.

• #2

  https://link.springer.com/article/10.1007/s00415-014-7598-y

  For those individuals in whom the above baseline investigations are unremarkable and/or where the family history and clinical features point towards a specific genetic diagnosis, it is then appropriate to test for the suspected mutation. […] There is considerable clinical utility for HSP families in detecting their causative mutation. It gives diagnostic certainty, prevents further unnecessary investigations and opens the possibility of predictive and prenatal testing. […] However, until very recently, in many healthcare systems, economic factors necessitated that genetic investigations were restricted to analysis of HSP genes in which there was the highest chance of detecting a mutation, as the expense of analysing rarely-causative genes was not justified by the low mutation detection rate per additional gene analysed.

• #3 Hereditary Spastic Paraplegia – Brain, Spinal Cord, and Nerve Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/spinal-cord-disorders/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia is diagnosed by excluding other disorders that cause similar symptoms (such as multiple sclerosis and spinal cord compression) and by determining whether other family members have hereditary spastic paraplegia. […] Blood tests to check for the genes that cause the disorder (genetic testing) are sometimes done. […] Consultation with a genetic counselor is recommended.

• #3 A Hundred Faces for a Unique Disorder: Hereditary Spastic Paraplegia

  https://www.imrpress.com/journal/JIN/23/6/10.31083/j.jin2306115/htm

  The differential diagnosis of HSP includes: the diplegic form of cerebral palsy; structural, vascular abnormalities and demyelinating disorders; amyotrophic lateral sclerosis; multiple sclerosis; nutritional disorders (including copper deficiency, Vitamin B12, and E deficiencies); and the large group of metabolic disorders for some of which an early diagnosis and early treatment may prevent the progression of the clinical signs. […] There is currently no definite cure for HSP. Symptomatic treatments aim to reduce symptoms severity and prevent complications. Available treatment may be used to manage symptoms: amelioration of spasticity; physical therapy including strengthening, stretching, balance, and agility exercise; reducing urinary urgency; and prevention of complications related to secondary cardiac dysfunction and to orthopedic complications.

• #3 Childhood Onset HSP | HSP Support Group

  https://hspgroup.org/childhood-onset-hsp/

  While hereditary spastic paraplegia (HSP) is more broadly known as an adult-onset rare neurological condition, it also affects children. […] The diagnosis of HSP in children in the UK usually begins with a comprehensive medical evaluation and neurological exam by a specialist, such as a neurologist or a geneticist. The doctor will review the child’s medical history, perform a physical examination, and assess the child’s motor skills, muscle tone, reflexes, and coordination. […] In general, genetic testing is required to confirm the diagnosis and identify the specific genetic mutation that is causing the disease. This may involve a blood or saliva test to analyse the child’s DNA. […] It’s important to note that the diagnostic process for HSP can be complex and may involve multiple tests and evaluations over time. A definitive diagnosis may take several months or even years to confirm, and may involve consultation with multiple medical specialists.

• #3 Is Hereditary Spastic Paraplegia a Disability? Not to This Girl.

  https://www.brainandlife.org/articles/a-six-year-old-with-hereditary-spastic-paraplegia-keeps-moving

  „The goal is to improve our understanding of pediatric-onset HSP, standardize assessments, and identify the best treatments for these patients.” […] Dr. Fink is encouraged by the pace of advancing research, which is focusing on three main areas. […] „None of us thinks of ourselves as just working on rare diseases, because we know we can apply the knowledge of what we find to other neurological conditions,” says Dr. Blackstone. […] The more science brings rare diseases together and links them in a common thread, the more likely it becomes that new therapies will emerge and interest major pharmaceutical companies.

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