Botulinum toxin (Botox) injection may be helpful when muscle tightness particular affects a limited number of muscles (e.g. Brain. 2015. https://doi.org/10.1136/jmedgenet-2014-102961. Hum Mutat. Neuropathology. Previously, it was considered that HSP caused symptoms only in the legs, and therefore, did not affect the strength or coordination of the arms and hands, or speech or swallowing. Rev Neurol (Paris). The study disclosed multiple pathogenic causes of 28 patients with suspected HSP though next-generation sequencing (NGS), and retrospectively analyzed clinic, laboratory, electromyographic and radiological data to summarize identification points. Spastic paraplegia type 5A is one of a group of genetic disorders known as hereditary spastic paraplegias. Cookies policy. Curr Opin Neurobiol. ARSACS was traditionally described as a trilogy, ataxia, pyramidal involvement, and axonal neuropathy. There are more than 80 different genetic types of HSP. Blackstone C. Converging cellular themes for the hereditary spastic paraplegias. Routine magnetic resonance imaging (MRI) of the brain is usually normal in uncomplicated HSP, and, depending on the genetic type and its neurologic features, in many forms of complicated HSP. Related Topics. The clinical presentation encompasses a variable degree of motor and sensory loss of the lower limbs, as well as bladder abnormalities and improper sphincter control. Prevalence of hereditary ataxia and spastic paraplegia in southeast Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, et al. Parkinsonism Relat Disord. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. This group of diseases . Hereditary Spastic Paraplegia. There also may be variation in severity and the nature of symptoms between affected family members. In the HSP group, ear of the lynx and thinning corpus callosum are common and characteristic findings for SPG11 (case 11 and 12) and SPG15 (case 13), especially for SPG11 [5, 8], and non-specific white matter lesions (case 14/SPG35) and cerebellar atrophy (case 15/SPG46) have been described. Synofzik M, Schule R. Overcoming the divide between ataxias and spastic paraplegias: shared phenotypes, genes, and pathways. Fink JK. Privacy Exercise programs should be developed by a neurologist, physiatrist, physical therapist or personal trainer who is experienced with HSP or similar disorders and should focus on the specific factors that make walking difficult for the specific individual. Rev Neurol (Paris) 2017 May;173:352-360. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n=17) matched for sex . National Spinal Cord Injury Statistical Center, Facts and Figures at a Glance. Medications such as oxybutynin may reduce urinary urgency. Combined with the clinical manifestations of the patients, we considered that they might be responsible lesions, and we would further conduct functional verification if possible. Hereditary spastic paraparesis (HSP) HSP is a group of nervous system disorders that cause weakness and stiffness or spasticity of the legs that get worse over time. Accessibility Several causative genes affect multiple of these functions, which are, most of the time, interconnected. Hereditary spastic paraplegia (HSP) is a syndromic designation for a clinically and genetically heterogeneous group of inherited neurodegenerative disorders in which the main neurological signs are lower-limb spasticity and weakness [1]. Paraparesis: Causes, Treatment, and More - Healthline What is hereditary spastic paraplegia? NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. Wang T, Guo H, Xiong B, Stessman HA, Wu H, Coe BP, et al. Pereira FS, Matte U, Habekost CT, de Castilhos RM, El Husny AS, Lourenco CM, et al. adductors or ankles). For these patients, daily exercise programs should focus on resistance exercises designed to maintain and very gradually increase the strength of these weak muscles. Treatment: management of symptoms Bookshelf Medscape. A. REEP1 c.17T>A, p.I6N B. FA2H c.1006C>G, p.H336D C. GBA2 c.2215G>T, p.D739Y D. MTHFR c.1808C>T, p.S603F E. POLR3A c.4044C>G, p.I1348M. Brain MRI of case 15/SPG46 showed cerebellar atrophy. a case 14/SPG35, FLAIR sequences showed hyperintensities in the white matter (A-C) b case22/X-ALD, FLAIR sequences demonstrated bilateral hyperintensities in the deep white matter, corpus callosum and internal capsules (D-F) c. case25/Krabbes Disease, FLAIR sequences showed hyperintensities in the corticospinal tracts starting in the precentral gyrus and extending to corona radiata, posterior limb of internal capsules, as well as in the terminal areas of white matter (G-I) d. case27/ARSACS, T2-FLAIR-sequencesshowed linear hypointensity in the pons and cerebellar atrophy (J-L). Hereditary Spastic Paraplegia Paralysis and Weakness. Brain. Detailed discussion of these alternative or co-existing diagnoses is beyond the scope of this review. Although many causal genes have been discovered with the development of genetic testing technology, there are still approximately in 5171% of all suspected cases of HSP without a genetic diagnosis [2, 5]. PDF Hereditary Spastic Paraplegia The main feature of the disease is progressive spasticity in the lower limbs due to pyramidal tract dysfunction. utilizing CRISPR/Cas9 methods) approaches offer additional treatment strategies. Genetic testing is most often able to find causative gene mutations for subjects with HSP who have a family history of a similarly affected first-degree relative. 55 Kenosia Avenue 2016 Feb;37(2):165-9 2006. https://doi.org/10.1038/ng1683. In addition to likely pathogenic and likely benign mutations, it is not uncommon for genetic testing to identify gene variations that are of uncertain significance. In addition, reversible signals in brain MRI could appear in MMA/MHTFR deficiency patients, such as case 16. The onset age of case 26 (SCAR8/SYNE1) was 13years old and case 27 (ARSACS/SACS) was 3years old, and the age of admission was 30 and 23years old respectively. 2022 Oct 24;11(21):3351. doi: 10.3390/cells11213351. Occasionally, dominantly inherited HSP skips a generation. Hereditary spastic paraplegias are often divided into two types: pure and complex. Chen W, Kubota S, Kim KS, Cheng J, Kuriyama M, Eggertsen G, et al. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis. It affects the nerves and causes progressive stiffness or spasticity and weakness in the lower body. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Cousyn L, Law-Ye B, Pyatigorskaya N, Debs R, Froissart R, Piraud M, et al. 6. 1. Axonal neuropathy was reported in the literatures, but, peripheral neuropathy is a rather infrequent feature in SYNE1 disease [48,49,50]. PubMed Central 2023 May 16;11(14):3288-3294. doi: 10.12998/wjcc.v11.i14.3288. Our perception of the intricate connections between clinical, genetic, and molecular aspects of neurodegenerative disorders has radically changed in recent years, thanks to improvements in genetic approaches. According to the standards of ACMG, the frameshift or nonsense mutations were pathogenic or likely pathogenic, while the five missense mutations were uncertain for pathogenicity. Walking pattern described as spastic gait occurs in which the following elements are present, each to variable degree in different individuals: a) heel strike is shifted forward (landing on the mid-foot or even further forward on the balls of the feet); b) there is reduced foot dorsiflexion (not bending the toes up, but instead tending to drag the toes, often catching them on carpet or when stepping over curbs, and causing the toes of the shoes to be worn out); c) stride length may become shorter; d) there may be circumduction or scissoring, with one leg crossing into the path of the other; e) there is a tendency for the knees to be maintained flexed (not fully extended in mid-stride), f) for thighs to be close together (adductor tightness), and g) hip flexion (knee lifting) to be reduced. There have been some reported exceptions to this however. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 9. Preventing further injury is critical to reducing the risk of permanent paralysis. 2019. https://doi.org/10.1111/jns.12348. All patients had spasm of lower limbs, and 2/5 (case 17 and 18) had positive Hoffmanns sign, and case 18 had hyperreflexia of the upper limbs. Hereditary spastic paraplegia: More than an upper motor neuron disease. 1900 Crown Colony Drive This is particularly true for hereditary spastic paraplegias, for which > 60 genes have been identified, highlighting (i) the considerable genetic heterogeneity of this group of clinically diverse disorders, (ii) the fuzzy border between recessive and dominant inheritance for several mutations, and (iii) the overlap of these mutations with other neurological conditions in terms of their clinical effects. Gleeson Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Knowing which specific muscles need strengthening, which specific muscles need spasticity-reduction (through medication, Botox injection, and stretching), and the degree of impairment of balance, speed, and precision of movement helps neurologists and physiatrists develop a proactive therapy approach to improve and maintain the ability to walk; and limit the cumulative impact of abnormal walking patterns on ankles, knees, hips, and spine. 2017. https://doi.org/10.1007/s12311-016-0803-z. SEP showed abnormalities of central segment in 2/4 cases (case 23 and 25), but EMG and NCS were normal in the two patients. Synofzik M, Nemeth AH. Cite this article. These syndromes are referred to as uncomplicated HSP. Neurol India. The occurrence of similarly affected family members is helpful in recognizing HSP but is not required for the diagnosis of HSP. PLoS One. 2012. https://doi.org/10.1371/journal.pone.0034195. This is particularly true for hereditary spastic paraplegias, for which > 60 genes have Update on the Genetics of Spastic Paraplegias Our perception of the intricate connections between clinical, genetic, and molecular aspects of neurodegenerative disorders has radically changed in recent years, thanks to improvements in genetic approaches. Conservation analysis was performed on the five new missense mutations, and we found that they were all located in highly conservative sequences (Fig. Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing. Terms and Conditions, Hereditary spastic paraplegia (HSP) describes a heterogeneous group of genetic neurodegenerative disorders in which the most severely a ected neurons are those of the spinal cord. Hereditary spastic paraplegias are a genetically heterogeneous group of neurological disorders. Each section has several vertebrae (singular is vertebra). Case 14 showed hyperintensity in the white matter, and enlargement of the pituitary gland. In those cases, a healthcare provider will provide guidance on what to do if and when paraplegia develops. In addition, for the case 24/HLD7, whether the variant c.4044C>G was pathogenic should be further evaluated, and follow-up was necessary. The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases. Spastic paraplegia is a neurological syndrome that may be seen in numerous conditions that affect the spinal cord, primarily of vascular and inflammatory origin. In addition, case 16 was readmitted 8 years later due to progressive mental decline and 1 month of psychiatric symptoms. Ann Neurol. Inspite of the fact that there was at least one change of the clinical features (neurological, dental, ophthalmic, and endocrine changes) in every HLD7 patient, case 24 only had spinal cord manifestations, so the variants of the patient need to be further verified for its pathogenicity, and follow-up was also very necessary. In: Rosenberg R, ed. Klebe S, Stevanin G, Depienne C. Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting. There may be significant variation in the severity of leg weakness (varying from none to marked), the degree of spasticity (varying from minimal to severe), and the occurrence of other neurologic symptoms between different genetic types of HSP; as well differences in the nature and severity of symptoms between individuals who have exactly the same genetic type of HSP. Despite discovery of more than 60 genes in which mutations cause various types of HSP, many individuals with HSP do not have an identified gene mutation. amyotrophic lateral sclerosis and primary lateral sclerosis). adrenomyeloneuropathy, mitochondrial myelopathy, spinocerebellar ataxia [SCA] including SCA3 and Friedreichs ataxia), cerebrotendinous xanthomatosis, copper deficiency (sometimes related to zinc toxicity), familial Alzheimers disease, [e.g. Mov Disord. Fink JK. Eur J Neurol. Although HSP is an upper motor neuron disease, the relevance of non-motor symptoms is increasingly recognized because of the potential response to treatment. Hereditary spastic paraplegia Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. NORD strives to open new assistance programs as funding allows. Cerebellum. Also, some cases of motor neuron involvement have been reported, emphasizing the role of AIFM1 in the development and function of motor neurons [52]. HSP can be transmitted in autosomal dominant (AD), autosomal recessive (AR), X-linked or mitochondrial maternal modes [4], with 1340% of cases being sporadic [5]. Clinical spectrum of AIFM1-associated disease in an Irish family, from mild neuropathy to severe cerebellar ataxia with colour blindness. Dysarthria in hereditary spastic paraplegia type 4 | Clinics Gene. Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. Depending on how it happens, this paralysis may have different effects on some body systems or processes. One caveat however: although early childhood-onset forms of HSP may be non-progressive, the degree of spasticity may increase slowly if adequate range-of-motion is not maintained through stretching exercises and muscle spasticity reduction. Ap4b1-knockout mouse model of hereditary spastic paraplegia type 47 displays motor dysfunction, aberrant brain morphology and ATG9A mislocalization. Falls (especially in older adults with bone density-related conditions like. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis. Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous disorders characterized by progressive spasticity, extremities weakness and dorsal column impairment. Browse by Disease. Those injuries can happen in many different ways. Birmingham, AL: University of Alabama at Birmingham, 2021. Recessive ataxias. Thirty-eight cases were applied in HSP-targeted sequencing, and we subsequently screened out 8 HSP cases with positive rate of 21%. An official website of the United States government. Hereditary spastic paraplegia is a group of inherited diseases characterized by a progressive gait disorder. In contrast, when HSP symptoms begin after early childhood (in adolescence or adulthood), symptoms usually worsen very slowly over a number of years. The only exceptions to this are when a healthcare provider diagnoses you with a medical condition that can lead to paraplegia. 1995;56(5):10529. Many individuals with HSP do not have similarly affected family members. [from HPO] Term Hierarchy GTR MeSH CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar CROGVSpastic paraplegia Disease Disorder by Site Disorder of nervous system Non-Neoplastic Nervous System Disorder Nerve palsy Paraplegia Spastic paraplegia Spastic paraplegia 7 (SPG7) is characterized by insidiously progressive bilateral leg weakness and spasticity. 2012. https://doi.org/10.1016/j.bbadis.2012.03.012. The ONLY exception to this is if the person is in immediate danger if you dont move them (such as from a motor vehicle crash where the vehicle the person is in may catch fire). Enhanced pituitary MRI showed no intensification. Adolescent/adult-onset homocysteine remethylation disorders characterized by gait disturbance with/without psychiatric symptoms and cognitive decline: a series of seven cases. [44] described that spinal cord syndrome existed for many years before the classic symptomatology became manifest in CTX, and tendinoxanthoma occurred in 71% of patients. Therefore, it is generally not possible to predict with certainty the severity or exact nature of symptoms associated with given genetic type of HSP. Neurosci Lett. 5. The best things you can do to prevent paraplegia or reduce your risk of developing it are: A healthcare provider should ALWAYS examine and treat paraplegia. The term paraplegia means severe weakness in both legs including paralysis. Chaudhry V, Moser HW, Cornblath DR. Nerve conduction studies in adrenomyeloneuropathy. Thereby, upper motor neuron signs were more likely to occur in the four extremities. Mutations in the CYP7B1 (SPG5), SPG7 (SPG7), SPG11 (SPG11), and ZFYVE26 (SPG15) genes are described as the most frequent causes for ARHSP [6]. Finsterer J, Loscher W, Quasthoff S, Wanschitz J, Auer-Grumbach M, Stevanin G. Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. The research was approved by the Ethical Committee of the Third Affiliated Hospital of Hebei Medical University and was conducted in accordance with the Declaration of Helsinki. Some of these diseases can manifest as not onlycomplicated HSP, such as HA, but pure forms, such as Krabbes disease and X-linked adrenoleukodystrophy (X-ALD) [4, 8]. HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. -galactocerebrosidase enzyme of case 25 was 2.6nmol/17h/mgPr, and the reference range was 1968.2nmol/17h/mgPr. Diagnosis is clinical and sometimes by genetic testing. Noreau A, Dion PA, Rouleau GA. Molecular aspects of hereditary spastic paraplegia. This impairs nerve transmission from the brain through the spinal cord. Signs and symptoms [ edit] Symptoms depend on the type of HSP inherited. Acta Neuropathol 2013;126:307-328. 2018. https://doi.org/10.1016/j.conb.2018.04.025. Phone: 203-744-0100 Hereditary Spastic Paraplegia Hereditary spastic paraplegia (HSP), also called familial spastic paraparesis (FSP), refers to a group of inherited disorders that are characterized by progressive weakness and spasticity (stiffness) of the legs. 1996. https://doi.org/10.1007/BF02265264. 2017. https://doi.org/10.1016/j.neurol.2017.03.034. Various types of HSP are classified according to a) the mode of inheritance (dominant, recessive, X-linked, maternal); b) the gene in which the mutation occurs; and c) the clinical syndrome (pattern of symptoms and neurologic findings). HSP is diagnosed by the following: 1) typical symptoms (lower extremity spastic weakness that may be non-worsening (early childhood onset) or slowly progressive over many years; 2) findings on neurologic examination (lower extremity hyperreflexia usually accompanied by some degree of spasticity and sometimes a specific pattern of muscle weakness); and 3) by the exclusion of alternate disorders (by history, examination, neuroimaging, and laboratory studies as needed). Lynch DS, Koutsis G, Tucci A, Panas M, Baklou M, Breza M, et al. Identifying a causative gene mutation can bring closure to a diagnostic odyssey, contribute insight into the prognosis and can be applied to genetic counseling and prenatal diagnosis. Periventricular hyperintensity was observed in case 16 and 17. J Neurol. Available at: http://emedicine.medscape.com/article/306713-overview Accessed June 21, 2017. The subtypes in the group included SPG3A/ATL1 (1/15)SPG4/SPAST (4/15)SPG5A/ CYP7B1 (2/15)SPG10/KIF5A (2/15)SPG11/SPG11 (2/15)SPG15/ZFYVE26 (1/15)SPG31/REEP1 (1/15)SPG35/FA2H (1/15) and SPG46/GBA2 (1/15). Both legs are affected, usually to a relatively similar degree. 1-3 Uncomplicated HSP is the most common and is .
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