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Autosomal Dominant Spastic Paraplegia Type 8

Autosomal Dominant Spastic Paraplegia 8


Presentation

  • Phenotypic homogeneity of the Huntington disease-like presentation in a SCA17 family. Neurology 2006;67(9):1701-3. Schneider SA, Walker RH, Bhatia KP.[books.google.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]
  • Dysphagia is present and Rombergism and pseudoathetosis are observed. NCVs and nerve biopsy reveal demyelinating and axonal features. Anti-GD1b or GQ1b (consistently present) antibodies, IgM paraproteins and cold agglutinins are present.[neuroweb.us]
  • Strabismus is present in a minority of patients. Systemic Features: Delayed global development, cognitive impairment, and intellectual disability are major features of this form of mental retardation. Hypotonia is present early.[disorders.eyes.arizona.edu]
  • Results: Patients differ in several categories depending on the type of mutation present.[jnnp.bmj.com]
Pain
  • ., University of Iowa · Peripheral and Autonomic Nervous System Disorders and Pain-Nicholas Maragakis, Johns Hopkins University · Neoplastic and Paraneoplastic Diseases-Lisa DeAngelis, Memorial Sloan-Kettering Cancer Center · Infectious Diseases of the[books.google.com]
  • Spastic paraplegia complex also affect the structure or function of the brain and peripheral nervous system consists of the nerves that connect the brain and spinal cord to muscles and sensory cells that detect sensation like touch, pain, heat, and sound[ivami.com]
  • […] and no pain.[neuroweb.us]
  • Diagram: Unlike flat feet, highly arched feet tend to be painful because more stress is placed on the section of the foot between the ankle and toes (metatarsals). This condition can make it difficult to fit into shoes.[hspjourney.blogspot.com]
Movement Disorder
  • She has always had a great interest in movement disorders with focus on movement disorder genetics and electrophysiology. She holds a Ph.D. degree in neurosciences from University College London.[books.google.com]
  • New chapters include ones on reproductive and metabolic disorders with AED use, and on movement disorders.[books.google.ro]
  • Sherwood, Drosophila Models of Hereditary Spastic Paraplegia, Movement Disorders, 10.1016/B978-0-12-405195-9.00073-1, (1103-1122), (2015).[doi.org]
Wheelchair Bound
  • The disorder has an adult-onset and some affected individuals become wheelchair-bound as the disease progresses. Management of spastic paraplegia includes regular physical therapy, assistive walking devices and ankle-foot orthotics.[cags.org.ae]
  • Some patients may become wheelchair-bound after several decades. Other features may include upper limb spasticity, impaired vibration sense in the distal lower limbs, and urinary urgency or incontinence (summary by {1:de Bot et al., 2013}).[diseaseinfosearch.org]
  • Disability was assessed on a five-point scale: 1, normal gait or very slight stiffness in the legs; 2, moderate gait stiffness; 3, unable to run but able to walk alone; 4, walk with help; 5, wheelchair-bound.[academic.oup.com]
  • She became wheelchair bound from the age of 43 years. Examination at the age of 63 years showed severe cerebellar ataxia in truncus and extremities.[journals.plos.org]
  • Although 95% of patients will show initial improvement following immunosuppressive therapy, the relapse rate is high. 64% improved and are able to return to work and 11% become bedridden or wheelchair bound.[neuroweb.us]
Hoarseness
  • The voice may be hoarse. Genetics Heterozygous mutations in the TLK2 gene (17q23) are responsible for this condition. Treatment Treatment Options: No treatment has been reported.[disorders.eyes.arizona.edu]
Vascular Disease
  • disease and infectious causes (HIV, Lyme disease, leprosy, hepatitis C).[neuroweb.us]
Long Arm
  • This process is due to mutations in the KIAA0196 gene, located on the long arm of chromosome 8 (8q24.13). This gene encodes the protein estrumpellina. Although its exact function is unknown, this protein is active throughout the body.[ivami.com]
  • Some people with IAHSP experience a deletion mutation in their ALS2 gene, located on the long arm of chromosome 2 at 2q33.2. HSP can be transmitted as an autosomal dominant, autosomal reseccive, or x-linked recessive trait.[disabled-world.com]
Suggestibility
  • The tests helped uncover a de-novo mutation (c.1669G A, p.Ala557Thr) in the KIAA0196 gene of one patient, suggesting a diagnosis of spastic paraplegia 8.[cags.org.ae]
  • The structure of the protein suggests that it may interact with the cellular cytoskeleton. They have identified at least three mutations in the gene KIAA0196 causing the spastic paraplegia type 8.[ivami.com]
  • Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet. PubMed PMID: 24973356 Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer's disease. N Engl J Med.[books.google.com]
  • On the basis of maximum LOD score of 1.94 at theta (max) 0 with marker D2S367, we obtained suggestive evidence for linkage of ADHSP to SPG4 locus.[link.springer.com]
  • CONCLUSIONS: To our knowledge, this is the first report describing SPG10-HSP outside Europe, which suggests KIF5A mutation is a shared genetic etiology for HSP over ethnicities.[neurology.org]
Incontinence
  • Patients also suffer from urinary urgency and incontinence. Hereditary spastic paraplegias have a combined prevalence of about 1 to 18 in 100,000 and SPG8 forms only a small percentage of these cases.[cags.org.ae]
  • Other features may include upper limb spasticity, impaired vibration sense in the distal lower limbs, and urinary urgency or incontinence (summary by {1:de Bot et al., 2013}).[diseaseinfosearch.org]
  • In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.[genecards.org]
  • 62% (87/141) Proximal muscle weakness in the lower limbs 54% (113/208) Distal muscle weakness in the lower limbs 36% (64/179) Distal muscle wasting 9% (16/176) Decreased vibration sense at ankles (abolished) 58% (111/208) (11% 24/208) Urinary urgency/incontinence[academic.oup.com]
  • He had symptoms of a neurogenic bladder, without incontinence. Electroencephalography (EEG), electromyography (EMG) and nerve conduction velocities (NCV) were normal.[journals.plos.org]
Hyperreflexia
  • Symptoms include hyperreflexia, extensor plantar responses, degeneration of the lateral corticospinal tracts, decreased vibratory sense in the lower limbs, pes cavus and atrophy of the shins.[cags.org.ae]
  • People with this condition may also have hyperreflexia, decreased ability to feel vibrations, muscular atrophy and decreased bladder control. Signs and symptoms of spastic paraplegia type 8 usually appear in early to mid-adulthood.[ivami.com]
  • Paraplegia 24, Autosomal Recessive Summaries for Spastic Paraplegia 24, Autosomal Recessive Symptoms & Phenotypes for Spastic Paraplegia 24, Autosomal Recessive Symptoms via clinical synopsis from OMIM: 57 Neurologic Central Nervous System: spasticity hyperreflexia[malacards.org]
  • Get Update Overview Spastic paraplegia-8 is an autosomal dominant neurologic disorder characterized by adult onset of progressive lower limb spasticity and hyperreflexia resulting in difficulty walking.[diseaseinfosearch.org]
  • People with this condition can also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, muscle wasting (amyotrophy), and reduced bladder control.[ghr.nlm.nih.gov]
Lower Extremity Spasticity
  • Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease.[ebi.ac.uk]
  • Spastic paraplegias are a diverse group of disorders in which the autosomal dominant forms are characterized by progressive, lower extremity spasticity caused by axonal degeneration in the terminal portions of the longest descending and ascending corticospinal[genecards.org]
  • Clinical Features  Symptoms depend on the type of HSP inherited  Main feature progressive spasticity in the lower limbs, due to pyramidal tract dysfunction  In the lower extremities, spasticity is increased at the hamstrings, quadriceps and ankles[slideshare.net]
Babinski Sign
  • Other common symptoms of HSP are urinary urgency and frequency, hyperactive reflexes, difficulty with balance, clonus, Babinski’s sign, diminished vibration sense in the feet, muscle spasms, and congenital foot problems such as pes cavus (high arched[sp-foundationorg.presencehost.net]
  • Examination at the age of 22 years after a traffic accident revealed failure of abduction of the left eye, hyperreflexia in all four extremities and Babinski sign.[journals.plos.org]
  • Babinski sign was negative. Video gait analysis was performed, which showed internal rotation of the hips and feet while walking and running. When walking barefooted she dragged the upper side of her toes, this was more pronounced when running.[omicsonline.org]
  • Clinically it is divided into a 'pure' or uncomplicated form with progressive spasticity as major symptom, associated with brisk reflexes, muscle weakness, positive Babinski's sign and urinary urgency as well as a 'complicated' form accompanied with other[link.springer.com]
  • Cranial neuropathies, particularly bilateral facial nerve palsy, transverse myelitis, spastic paraparesis, disturbances in micturition, Babinski sign are also observed during this stage.[neuroweb.us]
Spastic Gait
  • 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[rarediseases.org]
  • Diagnosis of SPG is established by the following clinical features 1, 2 : Typical clinical symptoms of spastic gait impairment and neurologic findings of spastic weakness, hyperreflexia, typically associated with bilateral extensor plantar responses A[centogene.com]
  • If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years.[en.wikipedia.org]
  • Winner B, Uyanik G, Gross C et al. (2004) Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11). Archives of Neurology 61: 117–121.[els.net]
  • Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus collasum in spastic gait gene 11 (SPG11). Arch Neurol 2004 ; 61 : 117 –21 Ohnishi J, Tomoda Y, Yokoyama K.[ajnr.org]
Neurologic Manifestation
  • Kosofsky, Weill-Cornell University Medical Center · Neurologic Manifestations of Medical Disorders-John C. Probasco, Johns Hopkins University[books.google.com]
  • Abetalipoproteinemia or Bassen-Kornzweig syndrome : Almost 50% of patients with abetalipoproteinemia present with neurological manifestations. Age of onset is usually in the 1 st or 2 nd decades of life.[neuroweb.us]

Workup

  • It is divided into the following sections: Overview Differential Diagnoses & Workup Treatment & Medication Follow-up Multimedia[hspersunite.org.au]
  • 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]
  • Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis.[link.springer.com]

Treatment

  • Fatemi Oxford University Press, ١٨‏/٠٨‏/٢٠١٦ - 1488 من الصفحات The second edition of Neurobiology of Disease includes nearly 200 articles surveying all major disorders of the nervous system in both adults and children, focusing on relevant diagnosis and treatments[books.google.com]
  • Treatment Treatment Options: No treatment has been reported.[disorders.eyes.arizona.edu]
  • Patients show clinical improvement with this treatment. Treatment options for surgery or destructive therapy is for lesions that don't respond to the above treatment.[en.wikipedia.org]
  • CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes.[diseaseinfosearch.org]

Prognosis

  • 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]
  • […] ataxia(1), 劣性遺伝(1), 統合脳・病態脳(55) 研究分野 内科系臨床医学 / 神経内科学 / 神経科学 / 神経科学一般 / 経歴 テキストで表示 1 2 3 2004年 - 2009年 新潟大学 脳研究所 教授 2003年 - 2004年 新潟大学 医学部 教授 2000年 国際医療福祉大学 教授 1999年 国際医療福祉大学 保健学部 教授 1998年 自治医科大学 医学部・神経内科 助教授 論文 テキストで表示 1 2 3 4 [Clinical features of poor-prognosis[researchmap.jp]
  • Favorable prognosis is indicated by preserved action potential preserved R1 or reappearance of R1 after 3 weeks. About 15% of patients will have permanent sequelae.[neuroweb.us]

Etiology

  • Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet. PubMed PMID: 24973356 Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer's disease. N Engl J Med.[books.google.com]
  • CONCLUSIONS: To our knowledge, this is the first report describing SPG10-HSP outside Europe, which suggests KIF5A mutation is a shared genetic etiology for HSP over ethnicities.[neurology.org]
  • Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet 1987 ; 41 : 933 –43 Goldblatt J, Ballo R, Sachs B, et al. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype.[ajnr.org]
  • Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability . Hum Mutat. 2017 Jun;38(6):621-636.[disorders.eyes.arizona.edu]
  • Tijana Copf, Impairments in dendrite morphogenesis as etiology for neurodevelopmental disorders and implications for therapeutic treatments, Neuroscience & Biobehavioral Reviews, 10.1016/j.neubiorev.2016.04.008, 68, (946-978), (2016).[doi.org]

Epidemiology

  • Recessive Epidemiology: Most Caucasian; 10 patients Clinical Onset age: 8 months to 7 years Extrapyramidal Dystonia Rigidity Choreoathetosis Cerebellum: Ataxia; Nystagmus Spasticity Mental development Poor speech Mental deficiency: Mild to Severe Other[neuromuscular.wustl.edu]
  • Sections address general anatomic, hormonal, epidemiologic, and drug aspects of women's health; neurologic conditions that arise during childhood, pregnancy, adulthood, and old age in females; and particular neurologic conditions that present differently[books.google.ro]
  • The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83.[invitae.com]
  • "Genetic epidemiology of Darier's disease: a population study in the west of Scotland". Br. J. Dermatol . 146 (1): 107–9. doi : 10.1046/j.1365-2133.2002.04559.x . PMID 11841374 . a b Burge SM, Wilkinson JD (July 1992).[en.wikipedia.org]
  • ., Epidemiological characteristics of hereditary spastic paraplegia in the Republic of Bashkortostan, Med. Genet. , 2013, vol. 12, no. 7, pp. 12–16. Google Scholar 4.[link.springer.com]
Sex distribution
Age distribution

Pathophysiology

  • DESIGN This is an observational study of autosomal dominant forms of hereditary spastic paraplegia progression, pathophysiology, and biomarkers.[clinicaltrials.gov]
  • 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]

Prevention

  • Affected patients must undergo regular neurological examinations to evaluate disease progression as well as urological analysis to prevent secondary complications such as urinary tract infections.[cags.org.ae]
  • Treatment No specific treatment is known that would prevent, slow, or reverse HSP Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being 26. Gen. Spas ticity Oral Agents Foc.[slideshare.net]
  • No treatments are currently available to prevent, stop, or reverse HSP.[sp-foundationorg.presencehost.net]
  • Treatment [ edit ] No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being.[en.wikipedia.org]
  • Even though physical therapy does not either prevent or reduce degenerative changes to the person's spinal cord, it is believed that receiving regular therapy can play an important part in assisting people with HSP to maintain and increase their muscle[disabled-world.com]

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