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Autosomal Recessive Spastic Paraplegia Type 18


Presentation

  • Autosomal recessive spastic paraplegia type 18 (SPG18) is a rare, complex type of HSP that presents in early childhood.[cags.org.ae]
  • He was awarded the 1st Distinguished Neurology Alumnus Award of the Neurological Institute; Columbia University Medical Center; 1994.He has been the Editor in Chief, JAMA Neurology (1997- present) and a member of the Editorial Board of JAMA (1997-present[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]
  • […] of life [ 6 ] but milder variations may not present until childhood.[patient.info]
  • Presentation on theme: "Spinal chord.[slideplayer.com]
Weakness
  • They also had symptoms of pseudobulbar palsy including increased jaw and glabellar reflexes and weak cough sound. They had mild-moderate distal pyramidal weakness, with only a flicker of movement at the fingers and forearms noted.[cags.org.ae]
  • Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking.[genecards.org]
  • […] and UMN findings ipsilateral to lesion 27 Syringomyelia Fluid filled cavitation in the center of the cord Cervical cord most common site Loss of pain and temperature related to the crossing fibers occurs early cape like sensory loss Weakness of muscles[slideplayer.com]
  • Based on patient's age at onset Type I 35 years Spasticity weakness muscle weakness urinary symptoms sensory loss spasticity 9.[slideshare.net]
  • Like all hereditary spastic paraplegias, spastic paraplegia type 8 involves spasticity of the leg muscles and muscle weakness.[ghr.nlm.nih.gov]
Disability
  • It is characterized by progressive spastic paraplegia associated with delayed motor development, severe intellectual disability and joint contractures. There is no treatment that can prevent or reverse nerve degeneration in HSP.[cags.org.ae]
  • MalaCards based summary : Spastic Paraplegia 18, also known as intellectual disability, motor dysfunction, and joint contractures , is related to spastic paraplegia 18, autosomal recessive and recessive intellectual disability-motor dysfunction-multiple[malacards.org]
  • SPG18  Mutation in Gene Erlin-2  Characterised by joint contractures and intellectual disability  Locus 8p11.23 Autosomalrecessive 16. Neuropathology . 17. Neuropathology cont…. 18. In Neuron Level Axonal Degeneration • Lesser Extent 19.[slideshare.net]
  • On the pediatric side, genetics is driven by neurodevelopmental disorders (including autism, intellectual disability, and epilepsy) and genetics of rare recessive disorders.[epilepsygenetics.net]
  • Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life.[en.wikipedia.org]
Epilepsy
  • Ingo Helbig is a child neurologist and epilepsy genetics researcher working at the Children’s Hospital of Philadelphia (CHOP), USA. He also leads the epilepsy genetics group at the University of Kiel, Germany.[epilepsygenetics.net]
  • Genetic Testing - Epilepsy-aphasia spectrum ..., (Epilepsy-aphasia spectrum) - Gen GRIN2A. Genetic Testing - epilepsy with febrile seizures generalized (Generalized epilepsy febrile seizures With) - Gen GABRG2.[ivami.com]
  • , juvenile myoclonic, susceptibility to, 8} 607628 600570 Autosomal dominant CLCN2 3q27.1 {Epilepsy, juvenile absence, susceptibility to, 2} 607628 600570 Autosomal dominant CLCN2 3q27.1 {Epilepsy, idiopathic generalized, susceptibility to, 11} 607628[mnglabs.com]
  • In some cases symptoms also include lactic acidosis, epilepsy, myopathy with ragged red fibres, and liver disease.[elsevier.es]
  • […] members in a pedigree, the association could have been coincidental, given the high prevalence of epilepsy in the community.[jnnp.bmj.com]
Developmental Delay
  • They all presented in the first 2 years of life with developmental delay, delayed walking, abnormal gait, and mild to severe mental retardation. They also had spasticity of the lower limbs, and a very thin corpus callosum.[cags.org.ae]
  • 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]
  • delay, and congenital heart defects Short stature, SHOX-linked Short-rib thoracic dysplasia with or without polydactyly Short-rib thoracic dysplasia with or without polydactyly 01 Short-rib thoracic dysplasia with or without polydactyly 02 Short-rib[moldiag.com]
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 617069 188250 Autosomal recessive TKT 3p21.1 Short stature, developmental delay, and congenital heart defects 617044 606781 Autosomal recessive TLL1 4q32.3 Atrial[mnglabs.com]
  • Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly.[ncbi.nlm.nih.gov]
Physician
  • This information is not intended to be patient education, does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.[diseaseinfosearch.org]
  • A Team of Genetic Counselors Genetic Counselors can provide information on the nature, inheritance and implications of genetic disorders to help the physician guide the patient and family in making informed medical and personal decisions.[1pdf.net]
  • Those cases were described more extensively in 1888 by Maurice Lorrain, a French physician. [8] Due to their contribution in describing the disease, it is still named Strümpell-Lorrain disease in French speaking countries.[en.wikipedia.org]
Cough
  • They also had symptoms of pseudobulbar palsy including increased jaw and glabellar reflexes and weak cough sound. They had mild-moderate distal pyramidal weakness, with only a flicker of movement at the fingers and forearms noted.[cags.org.ae]
  • Suctioning and cough assist device Management of Dysphagia Sialorrhea Management Glycopyrrolate (Robunil)- 1-2 mg every 4 hours Benztropine, Amitriptyline Transdermal hyoscine patch Topical atropine drops - 1% every 4 hours Botox or Myobloc injection[slideplayer.com]
Muscle Spasticity
  • Key words: hereditary spastic paraplegia; spastic paraplegia; muscle spasticity; genetics; mutation RESUMO Paraplegias espásticas hereditárias (PEH) constituem um grupo de desordens geneticamente determinadas caracterizadas por espasticidade e paraparesia[scielo.br]
Severe Mental Retardation
  • They all presented in the first 2 years of life with developmental delay, delayed walking, abnormal gait, and mild to severe mental retardation. They also had spasticity of the lower limbs, and a very thin corpus callosum.[cags.org.ae]
  • Severe mental retardation. SPG51 AP4E1 15q21.2 Adaptor-related protein complex 5, zeta 1 subunit Complicated: neonatal hypotonia that progresses to hypertonia. Severe mental retardation. Same phenotype as SPG50.[scielo.br]
  • X-LINKED LOCUS SPG1 The family with complicated HSP linked to SPG1 has marked phenotypic differences compared with the earlier pedigrees, which included the absence of cerebellar involvement, severe mental retardation, and congenital musculoskeletal abnormalities[jnnp.bmj.com]
Spastic Paraplegia
  • To date, 72 different spastic disease-loci have been identified, and 55 spastic paraplegia genes (SPGs) have already been cloned. Autosomal recessive spastic paraplegia type 18 (SPG18) is a rare, complex type of HSP that presents in early childhood.[cags.org.ae]
  • Spastic paraplegia type 8 is a pure hereditary spastic paraplegia. Like all hereditary spastic paraplegias, spastic paraplegia type 8 involves spasticity of the leg muscles and muscle weakness.[ghr.nlm.nih.gov]
  • Spastic paraplegia type 2 is part of a group of genetic disorders known as hereditary spastic paraplegias.[ghr.nlm.nih.gov]
  • Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. 2008 ; 7 : 1127 - 1138. 2. Fink, JK. Hereditary spastic paraplegia overview. In: Pagon RA, Adam MP, Ardinger HH, et al ., editors. GeneReviews.[cambridge.org]
  • spastic paraplegia (HSP) associated with pure or complicated phenotypes.[tmu.pure.elsevier.com]
Ataxia
  • MJD is now the most common autosomal domiant spinocerebellar ataxia world-wide.Dr. Rosenberg has published over 270 original scientific papers, chapters, reviews and editorials.[books.google.com]
  • Keywords: Recessive ataxia Friedreich ataxia Ataxia-telangiectasia Refsum disease Wilson disease Niemann-Pick disease type C Resumen Introducción Las ataxias espinocerebelosas de herencia recesiva constituyen un amplio grupo de enfermedades del cerebelo[elsevier.es]
  • EFNS Guidelines on the molecular diagnosis of ataxias and spastic paraplegias. Eur J NEurol 2010;17:179-188. Finsterer J. Ataxias with autosomal, X-choromosal or Maternal Inheritance. Can J Neurol Sci 2009; 36:409-428.[rarediseases.org]
  • 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]
  • Differential diagnosis Differential diagnoses include other autosomal recessive ataxias, such as Friedreich ataxia and ataxia with vitamin E deficiency (AVED), and hereditary forms of spastic paraplegia (see these terms), in particular spastic paraplegia[orpha.net]
Peripheral Neuropathy
  • See Hereditary Peripheral Neuropathies Testing Algorithm in Special Instructions Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Inherited peripheral neuropathies are a relatively[mayomedicallaboratories.com]
  • Onset of the peripheral neuropathy generally occurs later and leads to absence of the Achilles tendon reflex, distal amyotrophy and deep sensory disturbances (impaired vibration sense).[orpha.net]
  • CMT2X patients manifest a slowly progressive, peripheral neuropathy affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Some patients also have upper limb involvement. {ECO:0000269 PubMed:26556829}.[genecards.org]
  • neuropathy and mild cerebellar ataxia7 13 – 23 yrs AR Complicated Insidious progressive bilateral lower-limb weakness, spasticity.[1pdf.net]
  • .  additional symptoms in complicated form include: peripheral neuropathy, amyotrophy, ata xia, mentalretardation, ichthyosis, epile psy,optic neuropathy, dementia, deafne ss, or problems with speech, swallowing or breathing 22.[slideshare.net]
Cerebellar Ataxia
  • It is associated with a CYP7B1 founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients.[tmu.pure.elsevier.com]
  • 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, unspecified G12 Spinal muscular atrophy and related syndromes G12.0[icd10data.com]
  • Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology, 56 (2001), pp. 849-855 [35] M.C. Moreira, S. Klur, M. Watanabe, A.H. Nemeth, I. le Ber, J.C. Moniz, et al.[elsevier.es]
  • Also seizures, cerebellar ataxia, speech and swallowing problems, extra pyramidal signs and skeletal deformities may occur.[neurology.org]
  • Other early signs of cerebellar ataxia include dysarthria and nystagmus. The spasticity is progressive and eventually dominates the clinical picture. The pyramidal syndrome is characterised by brisk patellar tendon reflexes and the Babinski sign.[orpha.net]
Seizure
  • His 3-year-old sister had a similar course to him, but with the absence of seizures.[cags.org.ae]
  • In addition, the sister carrying the R294H variant had several prolonged febrile seizures; her sister only had a single febrile seizure. Spasticity was not noted at age 20 in the sister carrying the pathogenic variant. From EE to HSP.[epilepsygenetics.net]
  • Also seizures, cerebellar ataxia, speech and swallowing problems, extra pyramidal signs and skeletal deformities may occur.[neurology.org]
  • […] birth in 80 % of cases. [4] Most common location of ARACHNOID CYST SYLVIAN FISSURE (50% CASES) [5] Acute infantile SPINAL MUSCULAR ATROPHY is also nown as WERDNIG HOFFMAN DISEASE* [6] RASMUSSEN’S ENCEPHALITIS Progressive subacute unilateral intractable seizure[pguploads.wordpress.com]
  • Affects the legs only More common Bladder symptoms may occur eg “urgency” Complicated HSP  Spastic paraplegia with a variety of other problems  Other neurological problems eg ataxia (poor balance) Intellectual disability, dementia, extrapyramidal signs,Seizures[slideshare.net]

Workup

  • While this adds considerable challenges in the diagnostic workup, certain specific complicating features may guide the differential diagnosis between the different HSPs.[scielo.br]

Treatment

  • Nestler's research is to better understand the molecular mechanisms of addiction and depression based on work in animal models, and to use this information to develop improved treatments of these disorders.[books.google.com]
  • There is no treatment that can prevent or reverse nerve degeneration in HSP. Oman Al-Yahyaee et al. (2006) described two families diagnosed with autosomal recessive hereditary spastic paraplegia.[cags.org.ae]
  • Management and treatment Treatment is symptomatic aiming towards controlling the spasticity and should include physiotherapy, pharmacotherapy and use of ankle-foot orthoses. Prognosis Most patients become wheelchair-bound by the 5th decade of life.[orpha.net]
  • 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]
  • 37 Treatment Physical therapy Nerve and muscle trophic drugs Treatment of complications Treatment of heart disorders 38 Lateral Amiotrophic Sclerosis 39 Lateral Amiotrophic Sclerosis (ALS) Degenerative disease of the central nervous system Degeneration[slideplayer.com]

Prognosis

  • 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 Most patients become wheelchair-bound by the 5th decade of life. Death generally occurs during the sixth decade but survival into the seventies has been reported.[orpha.net]
  • 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]
  • Identification of the specific mutation concerned is essential to establishing a prognosis and providing satisfactory treatment and proper genetic counselling.[elsevier.es]
  • Disorders, the prognosis of which differs significantly from HSP, such as multiple sclerosis and familial motor neuron disease should also be excluded. The necessity for investigations will vary depending on the individual clinical picture.[jnnp.bmj.com]

Etiology

  • Accordingly, plasma oxysterols are biomarkers that should be included in the screening of any spastic paraplegia of unknown etiology.[oxfordmedicine.com]
  • Etiology ARSACS is caused by autosomal recessive mutations in the SACS gene (13q11), which encodes a large protein of unknown function named sacsin.[orpha.net]
  • The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.[genecards.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]

Epidemiology

  • Summary Epidemiology It was initially described in the Charlevoix-Saguenay region of Quebec where incidence of ARSACS at birth has been estimated at 1 in 1,932.[orpha.net]
  • Relevant External Links for SPG11 Genetic Association Database (GAD) SPG11 Human Genome Epidemiology (HuGE) Navigator SPG11 Atlas of Genetics and Cytogenetics in Oncology and Haematology: SPG11 No data available for Genatlas for SPG11 Gene Mutations in[genecards.org]
  • The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83.[invitae.com]
  • Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 2013;41:118-130. [ Links ]. Vanacore N, Bonifati V, Fabbrini G, et al. Epidemiology of multiple system atrophy.[scielo.br]
  • Epidemiology [ 6 ] This is a rare disease with an international incidence that is probably between 0.1 and 1 per 100,000 of the population.[patient.info]
Sex distribution
Age distribution

Pathophysiology

  • The group led by Giovanni Stevanin , INSERM/EPHE researcher, within the team of Alexis Brice at the ICM, has been working for the last several years on studying the genetic and pathophysiological mechanisms implicated in these disorders, and has already[icm-institute.org]
  • See Hereditary Peripheral Neuropathies Testing Algorithm in Special Instructions Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Inherited peripheral neuropathies are a relatively[mayomedicallaboratories.com]
  • Pathophysiology HSPs are characterized by retrograde degeneration of the longest neurons of the spinal cord, the corticospinal tract and the posterior columns 35.[scielo.br]
  • 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

  • This DNA vaccine has the potential to be a safe and effective therapy to prevent Alzheimer disease.He described Machado-Joseph disease (MJD), an autosomal dominant ataxia, with William Nyhan, M.D. Ph.D, in 1976, for the first time.[books.google.com]
  • There is no treatment that can prevent or reverse nerve degeneration in HSP. Oman Al-Yahyaee et al. (2006) described two families diagnosed with autosomal recessive hereditary spastic paraplegia.[cags.org.ae]
  • Con PREVENT se hace realidad un modelo de prevención de más de 300 enfermedades monogénicas recesivas, de forma FÁCIL, SEGURA y COSTE/EFICIENTE Qué es PREVENT, qué supone para ti PREVENT PREVENT consiste en incorporar Estudio de Idoneidad Genética (Matching[ceifer.com]
  • 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]
  • 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]

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