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X-Linked Spastic Paraplegia Type 2

SPG2


Presentation

  • Spastic paraplegia type 7 can often present with ataxia. 1 However, symptom onset in most of these cases is in the mid- to late-30s, which is later than symptom onset in the presented patient. 2 Clinical features, such as proximal weakness leading to[jamanetwork.com]
  • […] half of the patients presenting missense mutations.[jnnp.bmj.com]
  • HSP is classified according to the clinical phenotype as either pure or complex, the latter presenting with neurological and systemic impairments in addition to spastic paraparesis.[journals.lww.com]
  • Background: A 31 year old male presented with ten years of progressive walking difficulties, stiffness in his arms and legs, and distal paresthesias.[n.neurology.org]
  • Seizures may be present. Death usually occurs within the first decade of life.[ulf.org]
Disability
  • The disease spectrum for Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring[ncbi.nlm.nih.gov]
  • The mean disability score was 2.1. There is no significant difference between disability score and type of mutation.[jnnp.bmj.com]
  • […] centers, GPs Departments of regional hospital, diagnostic services, disability centers.[slideheaven.com]
  • Pure HSP kindreds The age of symptom onset, the rate of symptom progression, and the extent of disability are variable within and between HSP kindreds.[emedicine.medscape.com]
  • […] weight vest forward and lateral step up used to help motivate families to support child and motivate child to be active and optomistic Resting energy expenditure much lower and has a greater variety in those with cerebral palsy than those without the disability[quizlet.com]
Developmental Delay
  • His mother developed adult-onset mild spastic diplegia with dementia developing in later life, whereas his sister exhibited spastic diplegia from childhood, complicated by motor developmental delay and dysphagia.[ncbi.nlm.nih.gov]
  • […] and Mental Retardation with Facial Dysmorphism 2 Growth Mental Deficiency Syndrome of Myhre 1 Growth Retardation, Developmental Delay, Coarse Facies, and Early Death 2 Hadziselimovic Syndrome 0 Haspeslagh Fryns Muelenaere Syndrome 0 Holoprosencephaly[rgd.mcw.edu]
  • delay Developmental delay and marked lower limbs spasticity Delayed walking Speech delay (speech started at age 3 years) (speech started at age 2 and half years) - Speech dysarthria - Lower limbs Spasticity Markedly severe Markedly Severe Mild Back hypotonia[bmcmedgenet.biomedcentral.com]
  • Despite the prominent developmental delay of motor skills, patients often show slow development in the first decade of life, and then slowly deteriorate until death in mid-adulthood.[ulf.org]
  • Molecular genetic analysis is the best technique for carrier detection. [ 7 ] Presentation Generally, the clinical picture is one of: [ 2 ] Nystagmus Spastic quadriplegia Ataxia Developmental delay Typically, the disease begins in the first two months[patient.info]
Difficulty Walking
  • This leads to difficulty walking. As degeneration continues, symptoms worsen. [1] If only the lower body is affected, HSP is classified as uncomplicated or pure. HSP is classified as complicated or complex if other systems are involved.[rarediseases.info.nih.gov]
  • An early feature is difficulty walking due to spasticity and weakness, which typically affect both legs equally.[icdlist.com]
  • The primary symptom of HSP is difficulty walking due to weakness and tightness (spasticity) in the legs. Both legs are affected, usually to a relatively similar degree. The term “paraplegia” means severe weakness in both legs including paralysis.[rarediseases.org]
  • The hallmark of HSP is progressive difficulty walking due to increasingly weak and stiff (spastic) muscles. Symptoms appear in most people between the second and fourth decade of life, but they can start at any age.[sp-foundationorg.presencehost.net]
  • Most patients present with difficulty walking or gait disturbance, noticed either by themselves or a relative. In those with childhood onset, a delay in walking is not uncommon.[jnnp.bmj.com]
Progressive Dementia
  • He also developed progressive dementia and eventually became bed-ridden by 28 years after onset.[ncbi.nlm.nih.gov]
  • He also developed progressive dementia and eventually became bed-ridden by 28 years after… CONTINUE READING[semanticscholar.org]
Pallor
  • Histopathologically, the CNS showed widespread myelin pallor in the white matter. By contrast, the gray matter and peripheral nerves were well preserved.[ncbi.nlm.nih.gov]
  • There is diffuse myelin pallor of crossed and uncrossed corticospinal tracts. In addition, the gracile fasciculi in the centre of the dorsal columns show prominent myelin pallor. Anterior horn cells are normal in number and morphology.[jnnp.bmj.com]
Stridor
  • Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring hypotonia, respiratory distress, stridor[ncbi.nlm.nih.gov]
  • […] present at birth, and may include many of the following: Nystagmus: involuntary movements of the eyes Hypotonia: lack of muscle tone Ataxia: disturbance of gait (walking) or coordination Severe spasticity: tendency to have involuntary muscle contraction Stridor[ulf.org]
  • They often have stridor, respiratory difficulty and hypotonia . Seizures may occur. They have limited language, never walk and develop severe spasticity with little voluntary movement. They usually die in infancy or childhood.[patient.info]
Respiratory Distress
  • distress, stridor, nystagmus, and profound myelin loss.[ncbi.nlm.nih.gov]
  • Postnatally, he was admitted to the NICU because of respiratory distress; however, no mechanical ventilation was required. By the age of 4 months, his lower limbs were markedly spastic with scissoring.[bmcmedgenet.biomedcentral.com]
Pneumonia
  • In complicated SPG2 cases, patients deteriorate neurologically leading to a shorter life expectancy (between the fourth and seventh decade) typically from aspiration pneumonia, pulmonary embolism and other complications of generalized weakness.[rarediseases.info.nih.gov]
  • In complicated SPG2 cases, patients deteriorate neurologically leading to a shorter life expectancy (between the fourth and seventh decade) typically from aspiration pneumonia, pulmonary embolism and other complications of generalized weakness.Visit the[malacards.org]
Aspiration
  • In complicated SPG2 cases, patients deteriorate neurologically leading to a shorter life expectancy (between the fourth and seventh decade) typically from aspiration pneumonia, pulmonary embolism and other complications of generalized weakness.[rarediseases.info.nih.gov]
  • In complicated SPG2 cases, patients deteriorate neurologically leading to a shorter life expectancy (between the fourth and seventh decade) typically from aspiration pneumonia, pulmonary embolism and other complications of generalized weakness.Visit the[malacards.org]
Dysphagia
  • A 29-year-old man developed progressive spastic quadriplegia from early childhood with dysarthria, ataxia, dysphagia, and intellectual delay, but he displayed no nystagmus.[ncbi.nlm.nih.gov]
  • End-stage disease consisted of loss of spontaneous speech, severe dysphagia, spastic tetraplegia with peripheral nerve involvement and contractures.[rug.nl]
  • Less common features include difficulty swallowing (dysphagia), high-arched feet (pes cavus), an abnormal curvature of the spine (scoliosis), and involuntary movements of the eyes (nystagmus).[icdlist.com]
  • Mutations in VAMP1 gene are causing spastic ataxia 1 (SPAX1), a rare neurodegenerative disorder characterized by lower-limb spasticity and ataxia in the form of head jerks, ocular movement abnormalities, dysphagia, dysarthria, and gait disturbance 19[centogene.com]
Muscle Spasticity
  • Interestingly, it is our experience that AT lengthening will often reduce the degree of post-operative calf muscle spasticity as well.[medicaljournals.se]
  • Muscle spasticity and weakness can also be caused by other conditions including (but not limited to) Tropical Spastic Paraparesis and conditions called Lathyrism and Konzo caused by toxins in the plants lathyrus sativus and cassava that also cause muscle[sp-foundationorg.presencehost.net]
  • Many symptoms that are common in people with HSP are not directly caused by HSP but are instead caused indirectly by muscle spasticity, weakness, or hyperactive reflexes. Spasticity Spasticity is an increase in muscle tone with resulting stiffness.[emedicine.medscape.com]
  • Spasticity Paraplegia Spastic Paraplegia, Hereditary Muscular Diseases Musculoskeletal Diseases Muscle Hypertonia Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases Signs and Symptoms Paralysis Hereditary Sensory and Motor[clinicaltrials.gov]
  • 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.[rarediseases.org]
Suggestibility
  • Our observations suggest that genomic rearrangements that do not include PLP1 coding sequences should be considered as yet another potential mutational mechanism underlying PLP1-related dysmyelinating disorders.[ncbi.nlm.nih.gov]
  • […] below. 9 Further subdivision of pure HSP was also suggested by Harding based on the age of onset of the disease.[jnnp.bmj.com]
  • In Reply Ramirez-Zamora and Okun suggested that the conditions of spastic paraplegia type 7 (SPG7) and adult-onset Alexander disease should have been included in the discussion of the differential diagnoses.[jamanetwork.com]
  • Their father was said to be “a little lame,” suggesting that the mode of inheritance might be autosomal dominant ( Strumpell 1880 ).[medlink.com]
Spastic Paraplegia
  • PLP1 partial deletion is a rare cause of spastic paraplegia type 2 and exhibits X-linked dominant inheritance with variable expressivity.[ncbi.nlm.nih.gov]
  • […] analysis of L1CAM and PLP1 genes) Hereditary spastic paraplegia, AR and X-linked (NGS panel for 33 genes) - Plus[cgcgenetics.com]
Ataxia
  • A 29-year-old man developed progressive spastic quadriplegia from early childhood with dysarthria, ataxia, dysphagia, and intellectual delay, but he displayed no nystagmus.[ncbi.nlm.nih.gov]
  • G11.0 Congenital nonprogressive ataxia G11.1 Early-onset cerebellar ataxia G11.2 Late-onset cerebellar ataxia G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia[icd10data.com]
  • Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia.[karger.com]
  • Ataxia is evident once voluntary movements are acquired and affects virtually all patients. In milder cases, the ataxia affects their speech.[patient.info]
  • (SCAs), Friedreich ataxia, spastic ataxia of Charlevoix-Saguenay, etc.[centogene.com]
Peripheral Neuropathy
  • All three individuals had initially mild but progressive neurological phenotypes, no nystagmus, normal brainstem auditory-evoked potentials, and demyelinating peripheral neuropathy, but with varying clinical severity.[ncbi.nlm.nih.gov]
  • For example, a person with pure HSP may have peripheral neuropathy caused by diabetes, or he or she may have unrelated epilepsy. Additional symptoms The classic symptom of HSP is progressive difficulty in walking, but the severity varies.[emedicine.medscape.com]
  • In these cases, additional symptoms, including impaired vision, ataxia , epilepsy , cognitive impairment, peripheral neuropathy , and/or deafness, occur. [1] [2] The different forms of HSP are caused by mutations in different genes .[rarediseases.info.nih.gov]
  • For example, someone with uncomplicated HSP may have peripheral neuropathy caused by diabetes. As noted above, the severity of symptoms and age of onset can vary widely, even within the same family.[sp-foundationorg.presencehost.net]
Spastic Gait
  • The disease spectrum for Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring[ncbi.nlm.nih.gov]
  • There are a number of references which give descriptions of a spastic gait - here's part of one I like: When a person has a spastic gait, his legs are typically weak and abnormally stiff.[hspjourney.blogspot.com]
  • Abstract Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP.[thieme-connect.com]
  • gait and autonomic dysfunction.[malacards.org]
  • Orpha Number: 99015 Disease definition Spastic paraplegia type 2 (SPG2) is an X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction.[rarediseases.info.nih.gov]
Spastic Gait
  • The disease spectrum for Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring[ncbi.nlm.nih.gov]
  • There are a number of references which give descriptions of a spastic gait - here's part of one I like: When a person has a spastic gait, his legs are typically weak and abnormally stiff.[hspjourney.blogspot.com]
  • Abstract Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP.[thieme-connect.com]
  • gait and autonomic dysfunction.[malacards.org]
  • Orpha Number: 99015 Disease definition Spastic paraplegia type 2 (SPG2) is an X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction.[rarediseases.info.nih.gov]

Workup

  • High-arched feet (pescavus) are generally present and are usually prominent in older patients. workup Genetic Testing 43. Imaging Studies MRI scans may demonstrate atrophy of the spinal cord.[slideshare.net]
  • Methods: This paper reviews the pathophysiology, diagnostic workup, and management of balance impairments in hereditary spastic paraplegia.[medicaljournals.se]
  • Our findings confirm that this is indeed not an uncommon presentation of this disorder and we suggest that SPG7 gene analysis should be included in the diagnostic workup of autosomal recessive PEO, especially if spasticity is present.[journals.plos.org]

Treatment

  • The continuing definition of pathogenetic mechanisms operative in Pelizaeus-Merzbacher disease and spastic paraplegia type 2, together with advances in neural cell transplant therapy, augurs well for future treatment of the severe forms of Pelizaeus-Merzbacher[ncbi.nlm.nih.gov]
  • […] for each treatment [ Time Frame: 2 months ] 27-hydroxycholesterol will be measured on fasten blood samples for the 12 patients included before and after the 2-month treatment period for each treatment Secondary Outcome Measures : Modification of the[clinicaltrials.gov]
  • Food and Drug Administration has chosen Wave Life Sciences’ planned phase 2/3 study of suvodirsen, its lead experimental therapy for the treatment of Duchenne muscular dystrophy, to break new ground.[globalgenes.org]
  • If you’re seeking treatment for paralysis, ask your doctor for more information about your specific diagnosis, treatment plan, and long-term outlook.[healthline.com]
  • What is the treatment for PMD and SPG2? There is no treatment for PMD or SPG2; treatment is currently symptomatic and supportive.[ulf.org]

Prognosis

  • AB - Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited.[rug.nl]
  • SPG2 - these patients tend to have a normal lifespan. [ 6 ] There may appear to be periods of stability but the prognosis is for gradual deterioration.[patient.info]
  • Prognosis Pure SPG2 patients show a normal life expectancy.[rarediseases.info.nih.gov]
  • Prognosis: predicting symptoms and course of HSP As noted above, there is significant variation in HSP symptoms and their severity. This limits the certainty of making predictions.[rarediseases.org]
  • Prognosis [ edit ] Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals.[en.wikipedia.org]

Etiology

  • Accordingly, plasma oxysterols are biomarkers that should be included in the screening of any spastic paraplegia of unknown etiology.[oxfordmedicine.com]
  • Pure SPG2 manifests as early as infancy or early childhood ( Etiology SPG2 is due to missense substitutions affecting the PLP1 gene .[rarediseases.info.nih.gov]
  • MtDNA defects of either primary or secondary etiology are known to segregate predominantly in clinically affected tissues.[journals.plos.org]

Epidemiology

  • Consequently, they are often approached together in epidemiological studies.[karger.com]
  • Pugliatti M, Rosati G, Carton H et al (2006) The epidemiology of multiple sclerosis in Europe. Eur J Neurol 13:700–722 20.[slideheaven.com]
  • A community-based epidemiological survey of female urinary incontinence: the Norwegian EPINCONT study. Epidemiology of incontinence in the county of Nord-Trondelag. J Clin Epidemiol. 2000;53(11):1150–7.[ojrd.biomedcentral.com]
  • Epidemiology The prevalence and incidence of SPG2 have not been reported, but as part of the Pelizaeus-Merzbacher (PMD; see this term) spectrum, SPG2 roughly accounts for about 20 % of cases. There have been approximately 20 cases published on SPG2.[rarediseases.info.nih.gov]
  • The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83.[invitae.com]
Sex distribution
Age distribution

Pathophysiology

  • PATHOPHYSIOLOGY 6. Impaired cellular membrane trafficking 7. More particularly axonal transport of macromolecules and organelles. 8. Mutation of proteins, spastin and atlastin-1 causes impaired cellular membrane trafficking.[slideshare.net]
  • Methods: This paper reviews the pathophysiology, diagnostic workup, and management of balance impairments in hereditary spastic paraplegia.[medicaljournals.se]
  • Pathophysiology [ edit ] The major feature of HSP is a length dependent axonal degeneration. [21] These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis .[en.wikipedia.org]
  • Neurosurgery , London , UK 3 Department of Neurology and Neurosurgery , Institute of Emergency Medicine , Chisinau , Republic of Moldova 4 Division of Pathology , Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico , Milano , Italy 5 Department of Pathophysiology[jnnp.bmj.com]
  • Epidemiology, pathophysiology, and classification of fecal incontinence: state of the science summary for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) workshop. Am J Gastroenterol. 2015;110(1):127–36.[ojrd.biomedcentral.com]

Prevention

  • Preventing infections The key to preventing UTI is to halt the spread of bacteria into the bladder. Meticulous hygiene and proper handling of urinary care supplies can help prevent infection.[christopherreeve.org]
  • The findings, scientists say, could have important implications for the prevention and treatment of these kinds of metabolic diseases in humans.[elbiruniblogspotcom.blogspot.com]
  • Treating hereditary spastic paraplegia It isn't possible to prevent, slow or reverse hereditary spastic paraplegia, but some of the symptoms can be managed so that day-to-day activities become easier.[nhs.uk]
  • […] foot drop, pronation -control knee -increases ability to walk and do things without support of other people Physical Activity does what for people with CP 1. controls weight, improves chances of living longer, and helps prevent osteoporosis 2. sports[quizlet.com]
  • There are no specific treatments to prevent, slow, or reverse HSP. Individual symptoms may be treated with medications and/or physical therapy . [2] [3] Last updated: 4/24/2016[rarediseases.info.nih.gov]

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