Materiały źródłowe

• #1 Hereditary Spastic Paraplegia: An Update

  https://www.mdpi.com/1422-0067/23/3/1697

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. […] Hereditary spastic paraplegias (HSPs) are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.1–9.6 instances in every 100,000 around the world. […] The current need is to find a therapy applicable for various genes involved in HSPs. Identifying the biomarkers, such as chromosomal locus at its earlier stage, can provide more insight into the disease pathophysiology and cellular propagation networks. […] With the global prevalence of 0.1–9.6 in every 100,000 individuals, based on geographical location, HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations.

• #2 The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

  https://www.mdpi.com/1422-0067/23/14/7665

  Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). […] HSP is prevalent around the globe at a rate of 1–5 cases in every 100,000 individuals. […] According to a meta-analysis, the global prevalence of SPG is 1.8/100,000, with SPG3A, SPG4, and SPG11 subtypes predominating in registered cases and being infrequently diagnosed in consanguineous settings. […] The prevalence of familial inheritance is often higher than the sporadic form (2:1) in 70% of autosomal dominance linked to pure HSPs. […] To date, three HSPs are observed to be X-chromosome-linked and four mitochondrial genes cause HSP with a prevalence rate of 1–2% in the registered HSP cases. […] The presence of diverse genetic markers implies the existence of a wide range of clinical manifestations, from distinct pyramidal signs in the legs, primarily involving the upper motor neurons, to a group of other motor neurons to trigger other neurological manifestations, such as peripheral neuropathy, cognitive disability, and cerebellar ataxias.

• #3 Hereditary Spastic Paraplegia: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8835766/

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. HSPs are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.19.6 instances in every 100,000 around the world. HSPs can be triggered at infancy, toddling, puberty, or adulthood, with about 40% sporadic form. The critical manifestations include lower extremity bilateral spasticity, overactive reflexes, extensor plantar reflex, muscle fragility, and triggered gait deviations. HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations, with SPG4/SPAST mutations in 40%, SPG3A/ATL1 mutations in 10% at HSPs early beginning, about 10% SPG31/REEP1 mutations, and almost 3% SPG10/KIF5A mutations. On the other hand, AR HSPs are more complex and seen in a high degree of the consanguineous marriages population, with nearly 30% registered HSPs from the Middle East and northern Africa. SPG11 and SPG15 constitute a significant chunk of AR forms of HSPs. XLR HSPs shows complex phenotypes with few cases, and five HSPs are known to date with three genes identified as SPG22/SLC16A2, SPG1/L1CAM, and SPG2/PLP1.

• #4 Hereditary Spastic Paraplegia: An Update

  https://www.mdpi.com/1422-0067/23/3/1697

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. […] Hereditary spastic paraplegias (HSPs) are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.1–9.6 instances in every 100,000 around the world. […] The current need is to find a therapy applicable for various genes involved in HSPs. Identifying the biomarkers, such as chromosomal locus at its earlier stage, can provide more insight into the disease pathophysiology and cellular propagation networks. […] With the global prevalence of 0.1–9.6 in every 100,000 individuals, based on geographical location, HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations.

• #5 The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

  https://www.mdpi.com/1422-0067/23/14/7665

  Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). […] HSP is prevalent around the globe at a rate of 1–5 cases in every 100,000 individuals. […] According to a meta-analysis, the global prevalence of SPG is 1.8/100,000, with SPG3A, SPG4, and SPG11 subtypes predominating in registered cases and being infrequently diagnosed in consanguineous settings. […] The prevalence of familial inheritance is often higher than the sporadic form (2:1) in 70% of autosomal dominance linked to pure HSPs. […] To date, three HSPs are observed to be X-chromosome-linked and four mitochondrial genes cause HSP with a prevalence rate of 1–2% in the registered HSP cases. […] The presence of diverse genetic markers implies the existence of a wide range of clinical manifestations, from distinct pyramidal signs in the legs, primarily involving the upper motor neurons, to a group of other motor neurons to trigger other neurological manifestations, such as peripheral neuropathy, cognitive disability, and cerebellar ataxias.

• #6 Hereditary spastic paraplegia (HSP) | MedLink Neurology

  https://www.medlink.com/articles/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia has a global prevalence of 1.8 per 100,000 in their systemic review and meta-analysis of prevalence studies performed across various countries. A large, nationwide, epidemiological survey in Portugal reported the overall prevalence of hereditary spastic paraplegia at 4.1 per 100,000. In this survey, the prevalence of autosomal dominant hereditary spastic paraplegia was 5.6 per 100,000 and autosomal recessive hereditary spastic paraplegia was 3.3 per 100,000 population. However, large areas of the world remain without prevalence studies. Autosomal dominant, autosomal recessive, or X-linked modes of inheritance are reported, with 13% to 40% of cases being sporadic (ie, with no family history). […] There is significant variation in the reported prevalence of hereditary spastic paraplegia. This is likely due to the different genetic makeup of the populations and also methodical heterogeneity. In North American and north European hereditary spastic paraplegia populations, SPG4/SPAST mutations are evident in 40%, SPG3A/ATL1 mutations in 10%, SPG31/REEP1 mutations in 10%, and SPG10/KIF5A mutations in 3%. Autosomal recessive hereditary spastic paraplegias are more complex and seen in a high degree of the consanguineous marriage population, with nearly 30% registered hereditary spastic paraplegias from the Middle East and Northern Africa. SPG11 and SPG15 constitute a significant proportion of autosomal recessive forms of hereditary spastic paraplegias. Approximately 1% to 2% of cases show X and mitochondrial chromosomes mutations.

• #7 An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15 | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02595-4

  Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. […] The HSP global prevalence was estimated to be 3.6 per 100,000 for all HSP forms, whilst the estimated global prevalence per genetic subtype was 0.90 (SPG4), 0.22 (SPG7), 0.34 (SPG11), and 0.13 (SPG15), respectively. This equates to an estimated 3365 (SPG4) and 872 (SPG11) symptomatic patients, respectively, in the USA. […] This is the first epidemiological model of HSP prevalence at the genetic subtype-level reported at multiple geographic levels. This study offers additional data to better capture the burden of illness due to mutations in common genes causing HSP, that can inform public health policy and healthcare service planning, especially in regions with higher estimated prevalence of HSP.

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

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

  In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. A study by Ortega Suero et al estimated that the prevalence of HSP in Spain is 2.24 cases per 100,000 population. […] Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP. […] Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

• #9 Hereditary spastic paraplegia – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_spastic_paraplegia

  Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the United States, Hereditary Spastic Paraplegia is listed as a „rare disease” by the Office of Rare Diseases (ORD) of the National Institutes of Health which means that the disorder affects less than 200,000 people in the US population.

• #10 What is HSP? – HSP Research Foundation

  https://hspersunite.org.au/about-hsp/what-is-hsp/

  Hereditary Spastic Paraplegia (HSP) is a broad group of inherited, degenerative disorders characterised by impaired walking due to spasticity and weakness of the legs. […] The disease has been reported in nearly every country. Frequency estimates vary widely (from 0.5 to 12 people per 100,000 of population) and are an estimate or approximation as highly reliable data are not available. […] Based on the most recent and largest study so far on prevalence, a rate of 7.4/100,000 of population has been estimated. […] No differences in rate relating to gender have been found in most population studies, however in at least one larger study, prevalence in males was found to be significantly higher. […] Worldwide, HSP is thought to be under-diagnosed as mild cases (which go undiagnosed) exist.

• #11 Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-epidemiology-ataxia-hereditary-spastic-paraplegia-S2173580823000238

  Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study […] Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. […] We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. […] A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. […] In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. […] There is currently no epidemiological map of the types of ataxia and HSP in Spain.

• #12 Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study | Neurología (English Edition)

  https://www.elsevier.es/en-revista-neurologia-english-edition–495-articulo-epidemiology-ataxia-hereditary-spastic-paraplegia-S2173580823000238

  Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study […] Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. […] The total estimated prevalence of ataxia and HSP amounts to 7.73 cases/100 000 population. […] The estimated prevalence of ataxia in our series, according to the data from the participating communities, amounts to 5.48 cases per 100 000 population […] The estimated prevalence of HSP in the same age group amounts to 2.24 cases per 100 000 population. […] Our study estimates the prevalence of ataxia and HSP in Spain at 5.48 and 2.24 cases per 100 000 population, respectively. […] These rates are similar to those reported for other countries.

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

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

  In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. A study by Ortega Suero et al estimated that the prevalence of HSP in Spain is 2.24 cases per 100,000 population. […] Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP. […] Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

• #14 Hereditary spastic paraplegia – Wikipedia

  https://en.wikipedia.org/wiki/Hereditary_spastic_paraplegia

  Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the United States, Hereditary Spastic Paraplegia is listed as a „rare disease” by the Office of Rare Diseases (ORD) of the National Institutes of Health which means that the disorder affects less than 200,000 people in the US population.

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

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

  Hereditary Spastic Paraplegia (HSP) is a group of rare, inherited neurological disorders. Their primary symptoms are progressive spasticity and weakness of the leg and hip muscles. Researchers estimate that some 90 different types of HSP exist; the genetic causes are known for about fifty. The HSP incidence rate in the United States is about 20,000 people. The condition is characterized by insidiously progressive lower extremity weakness and spasticity. HSP is classified as uncomplicated or pure if neurological impairment is limited to the lower body. HSP is classified as complicated or complex if other systems are involved or if there are other neurological findings such as seizures, dementia, amyotrophy, extrapyramidal disturbance, or peripheral neuropathy in the absence of other disorders such as diabetes mellitus.

• #16 Hereditary Spastic Paraplegia Market Poised for Significant

  https://www.openpr.com/news/4003805/hereditary-spastic-paraplegia-market-poised-for-significant

  Hereditary spastic paraplegias treatment market is poised for significant expansion over the coming years, driven by advances in gene therapy, improved diagnostic capabilities, and growing research into targeted treatments for this rare neurological disorder. […] The epidemiological data presented in the report indicate key trends in incidence, demographics, and the hereditary spastic paraplegias patient pool. Hereditary spastic paraplegias affect roughly 0.1 to 9.6 individuals per 100K globally, with the US reporting approximately 3 cases per 100K. Japan’s prevalence is lower at around 0.2 per 100K. […] The current hereditary spastic paraplegias therapeutic landscape is limited to symptomatic management, as no disease-modifying treatments are currently available. […] Despite these advances, significant challenges remain in the hereditary spastic paraplegia market, including diagnostic delays, genetic heterogeneity, and the complexity of developing therapies for rare disease populations. […] Looking ahead, the hereditary spastic paraplegia market is expected to witness continued growth driven by increasing disease awareness, improved genetic testing capabilities, and the potential approval of novel disease-modifying therapies.

• #17

  https://omim.org/entry/182600

  Autosomal dominant spastic paraplegia has been mapped to chromosomes 9q (SPG19; 607152), 1p31-p21 (SPG29; 609727), 12q23-q24 (SPG36; 613096), 8p21.1-q13.3 (SPG37; 611945), 4p16-p15 (SPG38; 612335), and 11p14.1-p11.2 (SPG41; 613364). […] SPG3A is transmitted in an autosomal dominant pattern and may show incomplete penetrance (Durr et al., 2004). […] Varga et al. (2013) reported 2 unrelated families with hereditary spastic paraplegia in which family pedigree analysis suggested different inheritance patterns, but whole-exome sequencing identified pathogenic mutations in the ATL1 gene, consistent with SPG3A. […] Khan et al. (2014) reported a consanguineous Pakistani family in which 6 males presented with pure SPG before 2 years of age. […] In a nationwide survey of Japanese patients, Hirayama et al. (1994) estimated the prevalence of all forms of spinocerebellar degeneration to be 4.53 per 100,000; of these, 3.9% were thought to have hereditary spastic paraplegia.

• #18 An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15 | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02595-4

  The current epidemiology reports provide limited incidence and prevalence data since the association between genetic subtypes and clinical phenotypes remains incomplete due to small sample size or restricted studies, which, in turn, do not allow for a realistic estimation of the social burden of the disease, especially at the genetic subtype level. […] The estimated global prevalence was 0.90 per 100,000, and the estimated global patient pool was 70,320, which includes 33% of patients in Eastern and South-Eastern Asia; 11% in Europe; and 5% in North America. For SPG11, the estimated global prevalence was 0.34 per 100,000, and the estimated global patient pool was 26,839, with an estimated 29% of patients in Northern Africa and Western Asia; 9% in Europe; and 3% in North America. For SPG7, the estimated global prevalence was 0.22 per 100,000, and the estimated global patient pool was 16,793, with an estimated 28% of patients in Northern Africa and Western Asia; 10% in Europe; and 4% in North America. Finally for SPG15, the estimated global prevalence was 0.13 per 100,000, and the estimated global patient pool was 10,318, with an estimated 28% of patients in Northern Africa and Western Asia; 9% in Europe; and 4% in North America.

• #19 Hereditary Spastic Paraplegia: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8835766/

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. HSPs are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.19.6 instances in every 100,000 around the world. HSPs can be triggered at infancy, toddling, puberty, or adulthood, with about 40% sporadic form. The critical manifestations include lower extremity bilateral spasticity, overactive reflexes, extensor plantar reflex, muscle fragility, and triggered gait deviations. HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations, with SPG4/SPAST mutations in 40%, SPG3A/ATL1 mutations in 10% at HSPs early beginning, about 10% SPG31/REEP1 mutations, and almost 3% SPG10/KIF5A mutations. On the other hand, AR HSPs are more complex and seen in a high degree of the consanguineous marriages population, with nearly 30% registered HSPs from the Middle East and northern Africa. SPG11 and SPG15 constitute a significant chunk of AR forms of HSPs. XLR HSPs shows complex phenotypes with few cases, and five HSPs are known to date with three genes identified as SPG22/SLC16A2, SPG1/L1CAM, and SPG2/PLP1.

• #20 Hereditary Spastic Paraplegia: An Update

  https://www.mdpi.com/1422-0067/23/3/1697

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. […] Hereditary spastic paraplegias (HSPs) are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.1–9.6 instances in every 100,000 around the world. […] The current need is to find a therapy applicable for various genes involved in HSPs. Identifying the biomarkers, such as chromosomal locus at its earlier stage, can provide more insight into the disease pathophysiology and cellular propagation networks. […] With the global prevalence of 0.1–9.6 in every 100,000 individuals, based on geographical location, HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations.

• #21 Hereditary spastic paraplegia (HSP) | MedLink Neurology

  https://www.medlink.com/articles/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia has a global prevalence of 1.8 per 100,000 in their systemic review and meta-analysis of prevalence studies performed across various countries. A large, nationwide, epidemiological survey in Portugal reported the overall prevalence of hereditary spastic paraplegia at 4.1 per 100,000. In this survey, the prevalence of autosomal dominant hereditary spastic paraplegia was 5.6 per 100,000 and autosomal recessive hereditary spastic paraplegia was 3.3 per 100,000 population. However, large areas of the world remain without prevalence studies. Autosomal dominant, autosomal recessive, or X-linked modes of inheritance are reported, with 13% to 40% of cases being sporadic (ie, with no family history). […] There is significant variation in the reported prevalence of hereditary spastic paraplegia. This is likely due to the different genetic makeup of the populations and also methodical heterogeneity. In North American and north European hereditary spastic paraplegia populations, SPG4/SPAST mutations are evident in 40%, SPG3A/ATL1 mutations in 10%, SPG31/REEP1 mutations in 10%, and SPG10/KIF5A mutations in 3%. Autosomal recessive hereditary spastic paraplegias are more complex and seen in a high degree of the consanguineous marriage population, with nearly 30% registered hereditary spastic paraplegias from the Middle East and Northern Africa. SPG11 and SPG15 constitute a significant proportion of autosomal recessive forms of hereditary spastic paraplegias. Approximately 1% to 2% of cases show X and mitochondrial chromosomes mutations.

• #22 Hereditary Spastic Paraplegia: An Update

  https://www.mdpi.com/1422-0067/23/3/1697

  On the other hand, AR HSPs are more complex and seen in a high degree of the consanguineous marriages population, with nearly 30% registered HSPs from the Middle East and northern Africa. […] XLR HSPs shows complex phenotypes with few cases, and five HSPs are known to date with three genes identified as SPG22/SLC16A2, SPG1/L1CAM, and SPG2/PLP1.

• #23 Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias | Scientific Reports

  https://www.nature.com/articles/s41598-021-01635-2

  The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). […] Prevalence estimations of HSP in different geographical regions ranges from 2 to 10 per 100,000 individuals. […] However, there is a lack of epidemiological data about HSP in Latin America, with a few studies suggesting SPG4 as the most frequent autosomal dominant and SPG11 as the most frequent autosomal recessive HSP subtype in Brazil. […] Little is known about clinical and molecular epidemiology of childhood onset HSPs. […] Our study indicates that SPG4, closely followed by SPG3A, is the most frequent childhood-onset subtype in Brazil. […] A slightly predominance of complex forms (52%) was found among probands with childhood-onset HSP, which is similar to previous studies.

• #24 Frontiers | Case report: Hereditary spastic paraplegia with a novel homozygous mutation in ZFYVE26

  https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1160110/full

  Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with genetic and clinical heterogeneity characterized by spasticity and weakness of the lower limbs. It includes four genetic inheritance forms: autosomal dominant inheritance (AD), autosomal recessive inheritance (AR), X-linked inheritance, and mitochondrial inheritance. To date, more than 82 gene loci have been found to cause HSP, and SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs) with a thin corpus callosum (TCC), presents with early cognitive impairment and slowly progressive leg weakness. […] The prevalence is ~1.8/100,000. […] Until now, over 82 gene loci have been found to cause HSP. […] The pathogenesis of HSP remains unknown, and the axonal degeneration caused by the various types of HSP has different molecular pathogenesis. There are four modes of mutation, namely, AD, AR, X-linked inheritance, and mitochondrial inheritance.

• #25 Hereditary Spastic Paraparesis/Paraplegia – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/hereditary-spastic-paraplegia/

  HSP is a rare disease. It affects only about 0.007% of people worldwide. […] HSP occurs due to gene mutations. Two gene mutations are most often responsible when HSP begins in childhood. These are mutations in the SPG3A and SPG4 genes. However, over 80 genes are known to affect HSP. […] HSP is a genetic disorder. It can be caused by a mutation in any of a large number of genes. […] There is currently no cure for HSP. However, there are many treatments for the symptoms.

• #26 An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15 | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02595-4

  Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. […] The HSP global prevalence was estimated to be 3.6 per 100,000 for all HSP forms, whilst the estimated global prevalence per genetic subtype was 0.90 (SPG4), 0.22 (SPG7), 0.34 (SPG11), and 0.13 (SPG15), respectively. This equates to an estimated 3365 (SPG4) and 872 (SPG11) symptomatic patients, respectively, in the USA. […] This is the first epidemiological model of HSP prevalence at the genetic subtype-level reported at multiple geographic levels. This study offers additional data to better capture the burden of illness due to mutations in common genes causing HSP, that can inform public health policy and healthcare service planning, especially in regions with higher estimated prevalence of HSP.

• #27 Orphanet: Hereditary spastic paraplegia

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

  The prevalence of hereditary spastic paraplegia (HSP) is highly variable, ranging from 1/11,000-77,000 in Europe. […] Patterns of inheritance include mostly autosomal dominant and autosomal recessive, and rarely X-linked and mitochondrial. […] Management is symptomatic with physiotherapy, anti-spasticity drugs (baclofen, tizanidine, diazepam, botulinum toxin), and orthoses. […] Prognosis depends on the phenotype (pure/complex form), genotype, and is highly variable due to incomplete penetrance and variable gene expression.

• #28 Hereditary spastic paraplegia – UpToDate

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

  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.

• #29 The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

  https://www.mdpi.com/1422-0067/23/14/7665

  Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). […] HSP is prevalent around the globe at a rate of 1–5 cases in every 100,000 individuals. […] According to a meta-analysis, the global prevalence of SPG is 1.8/100,000, with SPG3A, SPG4, and SPG11 subtypes predominating in registered cases and being infrequently diagnosed in consanguineous settings. […] The prevalence of familial inheritance is often higher than the sporadic form (2:1) in 70% of autosomal dominance linked to pure HSPs. […] To date, three HSPs are observed to be X-chromosome-linked and four mitochondrial genes cause HSP with a prevalence rate of 1–2% in the registered HSP cases. […] The presence of diverse genetic markers implies the existence of a wide range of clinical manifestations, from distinct pyramidal signs in the legs, primarily involving the upper motor neurons, to a group of other motor neurons to trigger other neurological manifestations, such as peripheral neuropathy, cognitive disability, and cerebellar ataxias.

• #30

  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. […] The prevalence of AD HSP ranges from 0.5 to 5.5 per 100,000 and that of AR HSP from 0.3 to 5.3 per 100,000. […] In this review, we discuss current challenges to reach a genetic diagnosis in 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. […] There is a large overlap between HSP and other disorders such as inherited forms of hereditary ataxia, peripheral neuropathy, amyotrophic lateral sclerosis (ALS) and Parkinsons disease.

• #31 Hereditary Spastic Paraplegia: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8835766/

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. HSPs are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.19.6 instances in every 100,000 around the world. HSPs can be triggered at infancy, toddling, puberty, or adulthood, with about 40% sporadic form. The critical manifestations include lower extremity bilateral spasticity, overactive reflexes, extensor plantar reflex, muscle fragility, and triggered gait deviations. HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations, with SPG4/SPAST mutations in 40%, SPG3A/ATL1 mutations in 10% at HSPs early beginning, about 10% SPG31/REEP1 mutations, and almost 3% SPG10/KIF5A mutations. On the other hand, AR HSPs are more complex and seen in a high degree of the consanguineous marriages population, with nearly 30% registered HSPs from the Middle East and northern Africa. SPG11 and SPG15 constitute a significant chunk of AR forms of HSPs. XLR HSPs shows complex phenotypes with few cases, and five HSPs are known to date with three genes identified as SPG22/SLC16A2, SPG1/L1CAM, and SPG2/PLP1.

• #32

  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. […] The prevalence of AD HSP ranges from 0.5 to 5.5 per 100,000 and that of AR HSP from 0.3 to 5.3 per 100,000. […] In this review, we discuss current challenges to reach a genetic diagnosis in 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. […] There is a large overlap between HSP and other disorders such as inherited forms of hereditary ataxia, peripheral neuropathy, amyotrophic lateral sclerosis (ALS) and Parkinsons disease.

• #33 Hereditary Spastic Paraplegia | PM&R KnowledgeNow

  https://now.aapmr.org/hereditary-spastic-paraplegia/

  The prevalence of HSP is estimated to be at 3 to 10 cases per 100,000. The onset of the disease process begins anywhere from early childhood to 70 years of age. […] The mean age of onset for the most common autosomal-dominant HSP subtype (SPG4) is 31.7 years but cases have been reported with onset up to 70 years. […] Less than 30% of patient with HSP demonstrate an autosomal-recessive inheritance pattern. […] X-linked recessive inheritance patterns comprise 1-2% of HSP cases. […] The increasing number of genes being identified in association with HSP has led to the growing recognition about the heterogeneous nature of this disorder.

• #34 Hereditary spastic paraplegia (HSP) | MedLink Neurology

  https://www.medlink.com/articles/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia has a global prevalence of 1.8 per 100,000 in their systemic review and meta-analysis of prevalence studies performed across various countries. A large, nationwide, epidemiological survey in Portugal reported the overall prevalence of hereditary spastic paraplegia at 4.1 per 100,000. In this survey, the prevalence of autosomal dominant hereditary spastic paraplegia was 5.6 per 100,000 and autosomal recessive hereditary spastic paraplegia was 3.3 per 100,000 population. However, large areas of the world remain without prevalence studies. Autosomal dominant, autosomal recessive, or X-linked modes of inheritance are reported, with 13% to 40% of cases being sporadic (ie, with no family history). […] There is significant variation in the reported prevalence of hereditary spastic paraplegia. This is likely due to the different genetic makeup of the populations and also methodical heterogeneity. In North American and north European hereditary spastic paraplegia populations, SPG4/SPAST mutations are evident in 40%, SPG3A/ATL1 mutations in 10%, SPG31/REEP1 mutations in 10%, and SPG10/KIF5A mutations in 3%. Autosomal recessive hereditary spastic paraplegias are more complex and seen in a high degree of the consanguineous marriage population, with nearly 30% registered hereditary spastic paraplegias from the Middle East and Northern Africa. SPG11 and SPG15 constitute a significant proportion of autosomal recessive forms of hereditary spastic paraplegias. Approximately 1% to 2% of cases show X and mitochondrial chromosomes mutations.

• #35 Hereditary spastic paraplegia (HSP) | MedLink Neurology

  https://www.medlink.com/articles/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia has a global prevalence of 1.8 per 100,000 in their systemic review and meta-analysis of prevalence studies performed across various countries. A large, nationwide, epidemiological survey in Portugal reported the overall prevalence of hereditary spastic paraplegia at 4.1 per 100,000. In this survey, the prevalence of autosomal dominant hereditary spastic paraplegia was 5.6 per 100,000 and autosomal recessive hereditary spastic paraplegia was 3.3 per 100,000 population. However, large areas of the world remain without prevalence studies. Autosomal dominant, autosomal recessive, or X-linked modes of inheritance are reported, with 13% to 40% of cases being sporadic (ie, with no family history). […] There is significant variation in the reported prevalence of hereditary spastic paraplegia. This is likely due to the different genetic makeup of the populations and also methodical heterogeneity. In North American and north European hereditary spastic paraplegia populations, SPG4/SPAST mutations are evident in 40%, SPG3A/ATL1 mutations in 10%, SPG31/REEP1 mutations in 10%, and SPG10/KIF5A mutations in 3%. Autosomal recessive hereditary spastic paraplegias are more complex and seen in a high degree of the consanguineous marriage population, with nearly 30% registered hereditary spastic paraplegias from the Middle East and Northern Africa. SPG11 and SPG15 constitute a significant proportion of autosomal recessive forms of hereditary spastic paraplegias. Approximately 1% to 2% of cases show X and mitochondrial chromosomes mutations.

• #36 Hereditary spastic paraplegia (HSP) | MedLink Neurology

  https://www.medlink.com/articles/hereditary-spastic-paraplegia

  Hereditary spastic paraplegia has a global prevalence of 1.8 per 100,000 in their systemic review and meta-analysis of prevalence studies performed across various countries. A large, nationwide, epidemiological survey in Portugal reported the overall prevalence of hereditary spastic paraplegia at 4.1 per 100,000. In this survey, the prevalence of autosomal dominant hereditary spastic paraplegia was 5.6 per 100,000 and autosomal recessive hereditary spastic paraplegia was 3.3 per 100,000 population. However, large areas of the world remain without prevalence studies. Autosomal dominant, autosomal recessive, or X-linked modes of inheritance are reported, with 13% to 40% of cases being sporadic (ie, with no family history). […] There is significant variation in the reported prevalence of hereditary spastic paraplegia. This is likely due to the different genetic makeup of the populations and also methodical heterogeneity. In North American and north European hereditary spastic paraplegia populations, SPG4/SPAST mutations are evident in 40%, SPG3A/ATL1 mutations in 10%, SPG31/REEP1 mutations in 10%, and SPG10/KIF5A mutations in 3%. Autosomal recessive hereditary spastic paraplegias are more complex and seen in a high degree of the consanguineous marriage population, with nearly 30% registered hereditary spastic paraplegias from the Middle East and Northern Africa. SPG11 and SPG15 constitute a significant proportion of autosomal recessive forms of hereditary spastic paraplegias. Approximately 1% to 2% of cases show X and mitochondrial chromosomes mutations.

• #37 Hereditary Spastic Paraplegia: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8835766/

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. HSPs are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.19.6 instances in every 100,000 around the world. HSPs can be triggered at infancy, toddling, puberty, or adulthood, with about 40% sporadic form. The critical manifestations include lower extremity bilateral spasticity, overactive reflexes, extensor plantar reflex, muscle fragility, and triggered gait deviations. HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations, with SPG4/SPAST mutations in 40%, SPG3A/ATL1 mutations in 10% at HSPs early beginning, about 10% SPG31/REEP1 mutations, and almost 3% SPG10/KIF5A mutations. On the other hand, AR HSPs are more complex and seen in a high degree of the consanguineous marriages population, with nearly 30% registered HSPs from the Middle East and northern Africa. SPG11 and SPG15 constitute a significant chunk of AR forms of HSPs. XLR HSPs shows complex phenotypes with few cases, and five HSPs are known to date with three genes identified as SPG22/SLC16A2, SPG1/L1CAM, and SPG2/PLP1.

• #38 The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

  https://www.mdpi.com/1422-0067/23/14/7665

  Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). […] HSP is prevalent around the globe at a rate of 1–5 cases in every 100,000 individuals. […] According to a meta-analysis, the global prevalence of SPG is 1.8/100,000, with SPG3A, SPG4, and SPG11 subtypes predominating in registered cases and being infrequently diagnosed in consanguineous settings. […] The prevalence of familial inheritance is often higher than the sporadic form (2:1) in 70% of autosomal dominance linked to pure HSPs. […] To date, three HSPs are observed to be X-chromosome-linked and four mitochondrial genes cause HSP with a prevalence rate of 1–2% in the registered HSP cases. […] The presence of diverse genetic markers implies the existence of a wide range of clinical manifestations, from distinct pyramidal signs in the legs, primarily involving the upper motor neurons, to a group of other motor neurons to trigger other neurological manifestations, such as peripheral neuropathy, cognitive disability, and cerebellar ataxias.

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

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

  Hereditary Spastic Paraplegia (HSP) is a group of rare, inherited neurological disorders. Their primary symptoms are progressive spasticity and weakness of the leg and hip muscles. Researchers estimate that some 90 different types of HSP exist; the genetic causes are known for about fifty. The HSP incidence rate in the United States is about 20,000 people. The condition is characterized by insidiously progressive lower extremity weakness and spasticity. HSP is classified as uncomplicated or pure if neurological impairment is limited to the lower body. HSP is classified as complicated or complex if other systems are involved or if there are other neurological findings such as seizures, dementia, amyotrophy, extrapyramidal disturbance, or peripheral neuropathy in the absence of other disorders such as diabetes mellitus.

• #40 Hereditary Spastic Paraplegia – Neuropedia

  https://neuropedia.net/articles/neurology/hereditary-spastic-paraplegia/

  Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by motor neuron degeneration in the lower extremities, with relative sparing of the rest of the body. HSPs are generally considered non-life-threatening but are linked with a poor quality of life. They can be classified as pure or complex, the latter associated with additional neurological features. […] HSP is further divided according to the mode of inheritance, phenotype, and pathophysiology. The disease may be autosomal dominant, recessive, X-linked, or a mitochondrial trait. Moreover, the familial form is twice as widespread as the sporadic form in 70% of autosomal dominant HSP. Almost 80 spastic paraplegia genes (SPGs) are present, with an incidence of up to 5 to 100,000 individuals worldwide. […] Patients outcomes are highly variable and dependent on the associated genotype. Generally, patients with pure-type HSP have an average life expectancy and don’t suffer many complications. Hence, the prognosis is variable and dependent on the patients themselves.

• #41 The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

  https://www.mdpi.com/1422-0067/23/14/7665

  Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). […] HSP is prevalent around the globe at a rate of 1–5 cases in every 100,000 individuals. […] According to a meta-analysis, the global prevalence of SPG is 1.8/100,000, with SPG3A, SPG4, and SPG11 subtypes predominating in registered cases and being infrequently diagnosed in consanguineous settings. […] The prevalence of familial inheritance is often higher than the sporadic form (2:1) in 70% of autosomal dominance linked to pure HSPs. […] To date, three HSPs are observed to be X-chromosome-linked and four mitochondrial genes cause HSP with a prevalence rate of 1–2% in the registered HSP cases. […] The presence of diverse genetic markers implies the existence of a wide range of clinical manifestations, from distinct pyramidal signs in the legs, primarily involving the upper motor neurons, to a group of other motor neurons to trigger other neurological manifestations, such as peripheral neuropathy, cognitive disability, and cerebellar ataxias.

• #42 The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment

  https://www.mdpi.com/1422-0067/23/14/7665

  Inherited neurodegenerative pathology characterized by lower muscle tone and increasing spasticity in the lower limbs is termed hereditary spastic paraplegia (HSP). […] HSP is prevalent around the globe at a rate of 1–5 cases in every 100,000 individuals. […] According to a meta-analysis, the global prevalence of SPG is 1.8/100,000, with SPG3A, SPG4, and SPG11 subtypes predominating in registered cases and being infrequently diagnosed in consanguineous settings. […] The prevalence of familial inheritance is often higher than the sporadic form (2:1) in 70% of autosomal dominance linked to pure HSPs. […] To date, three HSPs are observed to be X-chromosome-linked and four mitochondrial genes cause HSP with a prevalence rate of 1–2% in the registered HSP cases. […] The presence of diverse genetic markers implies the existence of a wide range of clinical manifestations, from distinct pyramidal signs in the legs, primarily involving the upper motor neurons, to a group of other motor neurons to trigger other neurological manifestations, such as peripheral neuropathy, cognitive disability, and cerebellar ataxias.

• #43

  https://omim.org/entry/182600

  A number sign (#) is used with this entry because autosomal dominant spastic paraplegia-3A (SPG3A) is caused by heterozygous mutation in the ATL1 gene (606439) on chromosome 14q22. […] The hereditary spastic paraplegias are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). Zhao et al. (2001) noted that hereditary spastic paraplegia in the families of the SPG3A variety is characterized by early onset (before age 10 and usually before age 5 years). […] SPG is classified according to both the mode of inheritance (autosomal dominant, autosomal recessive (see 270800), and X-linked (see 303350)) and whether progressive spasticity occurs in isolation (’uncomplicated SPG’) or with other neurologic abnormalities (’complicated SPG’), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness.

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

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

  In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. A study by Ortega Suero et al estimated that the prevalence of HSP in Spain is 2.24 cases per 100,000 population. […] Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP. […] Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

• #45 SciELO Brazil – Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population

  https://www.scielo.br/j/anp/a/VkqR54NGVgBKQbtMPXGpxcy/?lang=en

  Studies involving HSP in children are scarce in the international literature. A recent study on historical aspects of these diseases points out the absence of such studies in Brazil. Our goals were to highlight the clinical and epidemiological aspects of pediatric HSP in a Brazilian sample. […] Thirty-five patients were studied, of whom 12 (34.2%) had HSP-S and 23 (65.8%) had HSP-C. […] The mean age at onset of symptoms was 2.9 years in HSP-S and 1.6 years in HSP-C (p = 0.023). The mean time between onset of symptoms and diagnosis was 3.0 years in HSP-S and 6.4 years in HSP-C. […] Complicated HSP was most frequently associated with intellectual disability. In our series, this association was present in 87% of the patients. […] There were no statistical differences between the simple and complicated groups in relation to skin color, sex, presence or absence of familial cases, and age at first appointment. However, there was a statistically significant difference regarding the age of onset of symptoms and the time elapsed between the onset of symptoms and final diagnosis between the two groups. […] All patients underwent brain MRI. Scans were normal in all patients with HSP-S. In patients with HSP-C, scans were normal in 10 (43.4%) patients, whereas in six (26.1%) patients nonspecific changes were present in white matter.

• #46 Hereditary spastic paraplegia – UpToDate

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

  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.

• #47 Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias | Scientific Reports

  https://www.nature.com/articles/s41598-021-01635-2

  The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). […] Prevalence estimations of HSP in different geographical regions ranges from 2 to 10 per 100,000 individuals. […] However, there is a lack of epidemiological data about HSP in Latin America, with a few studies suggesting SPG4 as the most frequent autosomal dominant and SPG11 as the most frequent autosomal recessive HSP subtype in Brazil. […] Little is known about clinical and molecular epidemiology of childhood onset HSPs. […] Our study indicates that SPG4, closely followed by SPG3A, is the most frequent childhood-onset subtype in Brazil. […] A slightly predominance of complex forms (52%) was found among probands with childhood-onset HSP, which is similar to previous studies.

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

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

  In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. A study by Ortega Suero et al estimated that the prevalence of HSP in Spain is 2.24 cases per 100,000 population. […] Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP. […] Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

• #49 Hereditary spastic paraplegia – Knowledge @ AMBOSS

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

  Hereditary spastic paraplegias (HSP) are a rare group of inherited neurodegenerative diseases which mainly affect the longest axons of the corticospinal tract and the dorsal column (which supply the lower limbs). […] Epidemiological data refers to the US, unless otherwise specified. […] Incidence: general population. […] Age of onset: variable (from early childhood till the 8th decade of life).

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

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

  In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. A study by Ortega Suero et al estimated that the prevalence of HSP in Spain is 2.24 cases per 100,000 population. […] Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP. […] Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

• #51 Hereditary Spastic Paraplegia | PM&R KnowledgeNow

  https://now.aapmr.org/hereditary-spastic-paraplegia/

  The prevalence of HSP is estimated to be at 3 to 10 cases per 100,000. The onset of the disease process begins anywhere from early childhood to 70 years of age. […] The mean age of onset for the most common autosomal-dominant HSP subtype (SPG4) is 31.7 years but cases have been reported with onset up to 70 years. […] Less than 30% of patient with HSP demonstrate an autosomal-recessive inheritance pattern. […] X-linked recessive inheritance patterns comprise 1-2% of HSP cases. […] The increasing number of genes being identified in association with HSP has led to the growing recognition about the heterogeneous nature of this disorder.

• #52 Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias | Scientific Reports

  https://www.nature.com/articles/s41598-021-01635-2

  SPG4 was the most frequent childhood-onset HSP in the present study, representing 22% of probands with solved genetic diagnosis, followed by SPG3A, representing 16% of probands. […] Our data confirmed the slow progression to handicap for SPG4 and SPG3A, which was in accordance with the slow cross-sectional SPRS progression for these subtypes. […] These results are paramount to understand the epidemiology of early-onset HSP in Brazil, as well as to understand better these disease progressions.

• #53 Hereditary Spastic Paraparesis/Paraplegia – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/hereditary-spastic-paraplegia/

  HSP is a rare disease. It affects only about 0.007% of people worldwide. […] HSP occurs due to gene mutations. Two gene mutations are most often responsible when HSP begins in childhood. These are mutations in the SPG3A and SPG4 genes. However, over 80 genes are known to affect HSP. […] HSP is a genetic disorder. It can be caused by a mutation in any of a large number of genes. […] There is currently no cure for HSP. However, there are many treatments for the symptoms.

• #54 SciELO Brazil – Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population

  https://www.scielo.br/j/anp/a/VkqR54NGVgBKQbtMPXGpxcy/?lang=en

  Studies involving HSP in children are scarce in the international literature. A recent study on historical aspects of these diseases points out the absence of such studies in Brazil. Our goals were to highlight the clinical and epidemiological aspects of pediatric HSP in a Brazilian sample. […] Thirty-five patients were studied, of whom 12 (34.2%) had HSP-S and 23 (65.8%) had HSP-C. […] The mean age at onset of symptoms was 2.9 years in HSP-S and 1.6 years in HSP-C (p = 0.023). The mean time between onset of symptoms and diagnosis was 3.0 years in HSP-S and 6.4 years in HSP-C. […] Complicated HSP was most frequently associated with intellectual disability. In our series, this association was present in 87% of the patients. […] There were no statistical differences between the simple and complicated groups in relation to skin color, sex, presence or absence of familial cases, and age at first appointment. However, there was a statistically significant difference regarding the age of onset of symptoms and the time elapsed between the onset of symptoms and final diagnosis between the two groups. […] All patients underwent brain MRI. Scans were normal in all patients with HSP-S. In patients with HSP-C, scans were normal in 10 (43.4%) patients, whereas in six (26.1%) patients nonspecific changes were present in white matter.

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

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

  In Europe, the frequency of HSP is estimated to be 1-9 cases per 100,000 population. A study by Ortega Suero et al estimated that the prevalence of HSP in Spain is 2.24 cases per 100,000 population. […] Because HSP is rare, it is often misdiagnosed, making the actual frequency difficult to determine. A reasonable estimate, however, is that it affects approximately 3 persons per 100,000 population. This represents fewer than 10,000 cases in the United States. Further estimates indicate that about 10% of people with HSP have complicated HSP. […] Pure HSP may occur at any age, from infancy through late adulthood. However, most patients experience the onset of symptoms between the second and fourth decades of life.

• #56 SciELO Brazil – Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population Hereditary spastic paraplegia: a clinical and epidemiological study of a Brazilian pediatric population

  https://www.scielo.br/j/anp/a/VkqR54NGVgBKQbtMPXGpxcy/?lang=en

  Studies involving HSP in children are scarce in the international literature. A recent study on historical aspects of these diseases points out the absence of such studies in Brazil. Our goals were to highlight the clinical and epidemiological aspects of pediatric HSP in a Brazilian sample. […] Thirty-five patients were studied, of whom 12 (34.2%) had HSP-S and 23 (65.8%) had HSP-C. […] The mean age at onset of symptoms was 2.9 years in HSP-S and 1.6 years in HSP-C (p = 0.023). The mean time between onset of symptoms and diagnosis was 3.0 years in HSP-S and 6.4 years in HSP-C. […] Complicated HSP was most frequently associated with intellectual disability. In our series, this association was present in 87% of the patients. […] There were no statistical differences between the simple and complicated groups in relation to skin color, sex, presence or absence of familial cases, and age at first appointment. However, there was a statistically significant difference regarding the age of onset of symptoms and the time elapsed between the onset of symptoms and final diagnosis between the two groups. […] All patients underwent brain MRI. Scans were normal in all patients with HSP-S. In patients with HSP-C, scans were normal in 10 (43.4%) patients, whereas in six (26.1%) patients nonspecific changes were present in white matter.

• #57 Frontiers | Case report: Hereditary spastic paraplegia with a novel homozygous mutation in ZFYVE26

  https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1160110/full

  Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with genetic and clinical heterogeneity characterized by spasticity and weakness of the lower limbs. It includes four genetic inheritance forms: autosomal dominant inheritance (AD), autosomal recessive inheritance (AR), X-linked inheritance, and mitochondrial inheritance. To date, more than 82 gene loci have been found to cause HSP, and SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs) with a thin corpus callosum (TCC), presents with early cognitive impairment and slowly progressive leg weakness. […] The prevalence is ~1.8/100,000. […] Until now, over 82 gene loci have been found to cause HSP. […] The pathogenesis of HSP remains unknown, and the axonal degeneration caused by the various types of HSP has different molecular pathogenesis. There are four modes of mutation, namely, AD, AR, X-linked inheritance, and mitochondrial inheritance.

• #58

  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. […] The genetic diagnosis of HSP is complex and can represent a major challenge for clinicians. […] 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.

• #59

  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. […] The prevalence of AD HSP ranges from 0.5 to 5.5 per 100,000 and that of AR HSP from 0.3 to 5.3 per 100,000. […] In this review, we discuss current challenges to reach a genetic diagnosis in 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. […] There is a large overlap between HSP and other disorders such as inherited forms of hereditary ataxia, peripheral neuropathy, amyotrophic lateral sclerosis (ALS) and Parkinsons disease.

• #60 MR Imaging Findings in Autosomal Recessive Hereditary Spastic Paraplegia | American Journal of Neuroradiology

  https://www.ajnr.org/content/30/5/936

  Hereditary spastic paraplegia (HSP) is a disorder characterized by degeneration of the corticospinal tracts and posterior column of the spinal cord. […] The MR imaging findings of HSP are nonspecific and variable; however, the most prominent features include atrophy of the corpus callosum, T2 signal intensity in the posterior limb of the internal capsule, and spinal cord atrophy. […] The radiologic findings of HSP are nonspecific, including mild-to-moderate brain atrophy, thinning of the corpus callosum, nonspecific white matter lesions in the cerebral hemispheres, abnormal T2 high signal intensity in the posterior limb of the internal capsules, and atrophy of the spinal cord. […] The severity of the findings was graded subjectively by the 2 neuroradiologists because, to our knowledge, there is no international standard rating scale for brain atrophy and white matter lesions. […] The MR imaging findings are nonspecific; however, the most known characteristic features include atrophy of the corpus callosum, T2 high signal intensity in the posterior limb of the internal capsule, and spinal cord atrophy.

• #61 Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses | Journal of Human Genetics

  https://www.nature.com/articles/jhg2013139

  Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. […] To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. […] The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP. […] Thus, the comprehensive molecular epidemiology of HSP is largely unestablished. […] To accomplish high sensitivities for detection of various kinds of mutations, we have conducted comprehensive mutational analyses incorporating custom-made resequencing microarrays, which enable comprehensive detection of single-nucleotide variations, custom-made comparative genomic hybridization (CGH) microarrays, which enable efficient detection of large insertion/deletion variants, and Sanger sequencing, which enables detection of small insertions/deletions in addition to single base substitutions.

• #62 Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias | Scientific Reports

  https://www.nature.com/articles/s41598-021-01635-2

  The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). […] Prevalence estimations of HSP in different geographical regions ranges from 2 to 10 per 100,000 individuals. […] However, there is a lack of epidemiological data about HSP in Latin America, with a few studies suggesting SPG4 as the most frequent autosomal dominant and SPG11 as the most frequent autosomal recessive HSP subtype in Brazil. […] Little is known about clinical and molecular epidemiology of childhood onset HSPs. […] Our study indicates that SPG4, closely followed by SPG3A, is the most frequent childhood-onset subtype in Brazil. […] A slightly predominance of complex forms (52%) was found among probands with childhood-onset HSP, which is similar to previous studies.

• #63 Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-epidemiology-ataxia-hereditary-spastic-paraplegia-S2173580823000238

  Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study […] Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. […] We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. […] A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. […] In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. […] There is currently no epidemiological map of the types of ataxia and HSP in Spain.

• #64 Hereditary Spastic Paraplegia: An Update

  https://www.mdpi.com/1422-0067/23/3/1697

  Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. […] Hereditary spastic paraplegias (HSPs) are a myriad of monogenic neurological defects aiding corticospinal and dorsal spinal cord axonal atrophy with a prevalence of 0.1–9.6 instances in every 100,000 around the world. […] The current need is to find a therapy applicable for various genes involved in HSPs. Identifying the biomarkers, such as chromosomal locus at its earlier stage, can provide more insight into the disease pathophysiology and cellular propagation networks. […] With the global prevalence of 0.1–9.6 in every 100,000 individuals, based on geographical location, HSP is mainly observed in AD pure form in about 80% of the North American and north European HSP populations.

• #65 MR Imaging Findings in Autosomal Recessive Hereditary Spastic Paraplegia | American Journal of Neuroradiology

  https://www.ajnr.org/content/30/5/936

  Hereditary spastic paraplegia (HSP) is a disorder characterized by degeneration of the corticospinal tracts and posterior column of the spinal cord. […] The MR imaging findings of HSP are nonspecific and variable; however, the most prominent features include atrophy of the corpus callosum, T2 signal intensity in the posterior limb of the internal capsule, and spinal cord atrophy. […] The radiologic findings of HSP are nonspecific, including mild-to-moderate brain atrophy, thinning of the corpus callosum, nonspecific white matter lesions in the cerebral hemispheres, abnormal T2 high signal intensity in the posterior limb of the internal capsules, and atrophy of the spinal cord. […] The severity of the findings was graded subjectively by the 2 neuroradiologists because, to our knowledge, there is no international standard rating scale for brain atrophy and white matter lesions. […] The MR imaging findings are nonspecific; however, the most known characteristic features include atrophy of the corpus callosum, T2 high signal intensity in the posterior limb of the internal capsule, and spinal cord atrophy.

• #66 Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153283

  Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system (pure forms). […] The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. […] We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. […] The ability of DTI to provide indications of the status of the cortico-spinal tract (CST), the Achilles heel of the central nervous system, suggests that this technique may complement the clinical measures and provide a more accurate quantification of disease severity and progression.

• #67 Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153283

  The neurophysiological assessment provided some confirmatory data and some novelties. A significant delay in LL mCCT was a constant feature in all but one patient, but the involvement of the motor and sensory tracts for the ULs found in a third of cases, even in absence of any clinical sign, is a clear indication that the condition is not exclusively affecting the longest tracts. […] Our results confirm for DTI technique a very interesting novel role, shading light on the microstructural organization of the brain in HSP patients in vivo. […] The predictive value of the indicators described in this paper can be established only through a prospective study, which is currently underway. Indeed, our expectation is that SPRS and DTI may serve as indicators of disease progression and could signal response to treatment.

• #68 Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153283

  The neurophysiological assessment provided some confirmatory data and some novelties. A significant delay in LL mCCT was a constant feature in all but one patient, but the involvement of the motor and sensory tracts for the ULs found in a third of cases, even in absence of any clinical sign, is a clear indication that the condition is not exclusively affecting the longest tracts. […] Our results confirm for DTI technique a very interesting novel role, shading light on the microstructural organization of the brain in HSP patients in vivo. […] The predictive value of the indicators described in this paper can be established only through a prospective study, which is currently underway. Indeed, our expectation is that SPRS and DTI may serve as indicators of disease progression and could signal response to treatment.

• #69 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2024.0234

  Hereditary spastic paraplegia (HSP) 76 is a rare form of spastic paraparesis caused by mutations in CAPN1. It is inherited in an autosomal recessive manner, and about 50 cases have been reported worldwide. […] The ear of the lynx sign has been observed in cases with HSP11, -15, and -78. Brain MRI in HSP76 cases has mostly produced normal results or revealed mild cerebellar atrophy, but the ear of the lynx sign was described in two HSP76 patients with ataxia. […] This report adds to the clinicoradiological and genetical spectrum of HSP76. We recommend considering genetic screening for recessive HSP in cases with the ear of the lynx sign.

• #70 An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15 | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02595-4

  This is the first reported epidemiological model to describe HSP prevalence at the genetic subtype level globally, as well as at the region and country-level. Given the limited available epidemiological evidence on HSP, this study offers additional data to better capture the burden of illness of this disease.

• #71 Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study | BMJ Open

  https://bmjopen.bmj.com/content/12/1/e054011

  Currently, there is no specific treatment for any form of HSP. The development of improved treatment methods requires a better understanding of the natural history of the disease. […] Understanding the mechanistic contributions of HSP subtypes to disease variety and severity will allow for data set integration and an attempt to employ innovative means of classifying HSPs according to their molecular mechanisms.

• #72

  https://www.dzne.de/en/research/studies/clinical-studies/hsp-net/

  Hereditary spastic paraplegia (HSP) is a rare, slowly progressing disease that characteristically causes patients to have spastic gaits. The HSP project calls for the establishment and execution of a multicentric study on the natural longitudinal course of hereditary spastic paraplegia. […] It affects an average of only 2-4 out of every 100,000 persons, in the course of their lives. […] The research is aimed especially at identifying new genetic causes of HSP. […] In cases in which no genetic causes have been identified, genetic testing for all known HSP genes will be carried out. […] In family groups in which the causes of the disease remain unclear, a search for new HSP genes will be conducted, entailing sequencing of all gene regions that encode information for human-protein formation.

• #73

  https://www.dzne.de/en/research/studies/clinical-studies/hsp-net/

  Hereditary spastic paraplegia (HSP) is a rare, slowly progressing disease that characteristically causes patients to have spastic gaits. The HSP project calls for the establishment and execution of a multicentric study on the natural longitudinal course of hereditary spastic paraplegia. […] It affects an average of only 2-4 out of every 100,000 persons, in the course of their lives. […] The research is aimed especially at identifying new genetic causes of HSP. […] In cases in which no genetic causes have been identified, genetic testing for all known HSP genes will be carried out. […] In family groups in which the causes of the disease remain unclear, a search for new HSP genes will be conducted, entailing sequencing of all gene regions that encode information for human-protein formation.

• #74 An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15 | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02595-4

  This is the first reported epidemiological model to describe HSP prevalence at the genetic subtype level globally, as well as at the region and country-level. Given the limited available epidemiological evidence on HSP, this study offers additional data to better capture the burden of illness of this disease.

• #75 Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study | BMJ Open

  https://bmjopen.bmj.com/content/12/1/e054011

  Currently, there is no specific treatment for any form of HSP. The development of improved treatment methods requires a better understanding of the natural history of the disease. […] Understanding the mechanistic contributions of HSP subtypes to disease variety and severity will allow for data set integration and an attempt to employ innovative means of classifying HSPs according to their molecular mechanisms.

• #76

  https://journals.lww.com/jbioxresearch/fulltext/2022/06000/hereditary_spastic_paraplegia_type_56__what_a.2.aspx

  Hereditary spastic paraplegia type 56 (SPG56-HSP) is a rare autosomal recessive disorder caused by loss of function mutations in CYP2U1, leading to an early-onset limbs spasticity, often complicated by additional neurological or extra-neurological manifestations. Given its low prevalence, the molecular bases underlying SPG56-HSP are still poorly understood, and effective treatment options are still lacking. […] SPG56-HSP is one of the least frequent HSP subtypes (prevalence 1/1,000,000), estimated affecting 1.5% of HSP patients. […] As for other forms of HSPs, the extreme phenotypic heterogeneity observed in these SPG56-HSP families cannot be entirely explained by the causative mutation itself. Further analyses aimed to identify additional genetic, epigenetic, and environmental factors acting as modifiers could help unveil the various players contributing to SPG56-HSP variability.

• #77 What is HSP? – HSP Research Foundation

  https://hspersunite.org.au/about-hsp/what-is-hsp/

  Overall, total numbers with HSP are likely to be underestimated. […] At present there is no cure for HSP, nor any way to reverse the disease nor halt its progress. […] Research to find an effective treatment for HSP has been and remains the major focus of the Foundation. […] The HSP Research Program initiated in 2007 has proved highly successful. […] A huge challenge for HSP clinical trials is the lack of a reliable, valid and widely-accepted measure of HSP status.

• #78 An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15 | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02595-4

  Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. […] The HSP global prevalence was estimated to be 3.6 per 100,000 for all HSP forms, whilst the estimated global prevalence per genetic subtype was 0.90 (SPG4), 0.22 (SPG7), 0.34 (SPG11), and 0.13 (SPG15), respectively. This equates to an estimated 3365 (SPG4) and 872 (SPG11) symptomatic patients, respectively, in the USA. […] This is the first epidemiological model of HSP prevalence at the genetic subtype-level reported at multiple geographic levels. This study offers additional data to better capture the burden of illness due to mutations in common genes causing HSP, that can inform public health policy and healthcare service planning, especially in regions with higher estimated prevalence of HSP.

• #79

  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. […] The prevalence of AD HSP ranges from 0.5 to 5.5 per 100,000 and that of AR HSP from 0.3 to 5.3 per 100,000. […] In this review, we discuss current challenges to reach a genetic diagnosis in 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. […] There is a large overlap between HSP and other disorders such as inherited forms of hereditary ataxia, peripheral neuropathy, amyotrophic lateral sclerosis (ALS) and Parkinsons disease.

• #80 Hereditary Spastic Paraplegia Market Poised for Significant

  https://www.openpr.com/news/4003805/hereditary-spastic-paraplegia-market-poised-for-significant

  Hereditary spastic paraplegias treatment market is poised for significant expansion over the coming years, driven by advances in gene therapy, improved diagnostic capabilities, and growing research into targeted treatments for this rare neurological disorder. […] The epidemiological data presented in the report indicate key trends in incidence, demographics, and the hereditary spastic paraplegias patient pool. Hereditary spastic paraplegias affect roughly 0.1 to 9.6 individuals per 100K globally, with the US reporting approximately 3 cases per 100K. Japan’s prevalence is lower at around 0.2 per 100K. […] The current hereditary spastic paraplegias therapeutic landscape is limited to symptomatic management, as no disease-modifying treatments are currently available. […] Despite these advances, significant challenges remain in the hereditary spastic paraplegia market, including diagnostic delays, genetic heterogeneity, and the complexity of developing therapies for rare disease populations. […] Looking ahead, the hereditary spastic paraplegia market is expected to witness continued growth driven by increasing disease awareness, improved genetic testing capabilities, and the potential approval of novel disease-modifying therapies.

• #81 Spastic paraplegia type 15 | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/spastic-paraplegia-type-15/

  Hereditary spastic paraplegias are a group of disorders that cause progressive muscle stiffness (spasticity) in the lower limbs, leading to paralysis (paraplegia). […] Incidence of autosomal-recessive hereditary spastic paraplegias is approximately 1 in 50,000 births. SPG15 accounts for 3 to 15% of cases of autosomal-recessive hereditary spastic paraplegias, depending on region. In areas where relatedness between parents of offspring (consanguinity) is common, the frequency of cases is likely higher. […] The Spastic Paraplegia Foundation is a non-profit organization dedicated to providing information about these conditions, creating opportunities for support and sharing, and funding research towards discovering the cures for hereditary spastic paraplegias and primary lateral sclerosis.

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