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Autosomal Dominant Spastic Paraplegia Type 13

Autosomal Dominant Spastic Paraplegia 13


Presentation

  • It presents the clinical phenotypes of the most commonly inherited neurologic diseases, and their molecular pathogenesis, followed by a description of the appropriate tests to be used in diagnosis.[books.google.de]
  • 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]
  • When present, autonomic disturbances manifest as hypohydrosis.[avensonline.org]
  • Small hands and sometimes joint laxity are commonly present. Cervical spine abnormalities including clefting, improper fusion, and segmentation anomalies are common. Brain MRI may be normal but a small corpus callosum was present in some patients.[disorders.eyes.arizona.edu]
  • The sister carrying the R294H variant had an ataxic gait and hand tremor at 3 years, which was not present in her sister.[epilepsygenetics.net]
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.de]
  • Patients with HSAN-I suffer from loss of pain and temperature sensation beginning in the lower limbs and spreading proximally.[avensonline.org]
  • In addition to the muscles and brain, spastic paraplegia type 15 affects the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound[ghr.nlm.nih.gov]
Movement Disorder
  • To further enhance the scope and quality of this new edition, the following Section Editors provided oversight of their respective sections: · Movement Disorders-Joel Perlmutter, Washington University · Dementias-David Knopman, Mayo Clinic · Motorneuron[books.google.de]
  • Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force. Movement Disorders , 31(4), 436-457.[sydney.edu.au]
  • Sherwood , Drosophila Models of Hereditary Spastic Paraplegia , Movement Disorders , 10.1016/B978-0-12-405195-9.00073-1 , (1103-1122) , (2015) .[doi.org]
  • Movement Disord 2016; 31: S227-S.[hih-tuebingen.de]
Physician
  • Pulst Oxford University Press, 2000 - 458 Seiten Neurogenetics is intended for any physician or scientist who manages patients with inherited diseases of the nervous system.[books.google.de]
  • 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]
  • Signs are the objective evidence of the disorder, documented, for example by physician examination, laboratory studies, or magnetic resonance images (MRI).[rarediseases.org]
  • Editor’s Note: One of our community members, who is a primary care physician with HSP, submitted an article about pain management. Please see Articles – Pain. Most people with HSP have uncomplicated HSP.[sp-foundationorg.presencehost.net]
Developmental Disabilities
  • disability, and seizures 617157 610087 Autosomal recessive PRNP 20p13 {Kuru, susceptibility to} 245300 176640 PRNP 20p13 Huntington disease-like 1 603218 176640 Autosomal dominant PRNP 20p13 Cerebral amyloid angiopathy, PRNP-related 137440 176640 Autosomal[mnglabs.com]
Pathologist
  • PMID: 24603320 Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion[invitae.com]
Proximal Muscle Weakness
  • 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 38% (74[academic.oup.com]
Prominent Occiput
  • Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia.[genecards.org]
Hyperreflexia
  • 33 HP:0002395 Symptoms via clinical synopsis from OMIM: 58 Neurologic Central Nervous System: lower limb spasticity ankle clonus spastic gait lower limb hyperreflexia extensor plantar responses more Neurologic Peripheral Nervous System: decreased vibration[malacards.org]
  • 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 can also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, muscle wasting (amyotrophy), and reduced bladder control.[ghr.nlm.nih.gov]
  • Clinical Characteristics Clinical Description Spastic paraplegia 8 (SPG8) is characterized by progressive lower-limb spasticity (hyperreflexia and extensor plantar reflexes).[ncbi.nlm.nih.gov]
Spastic Gait
  • gait 60 33 occasional (7.5%) Occasional (29-5%) HP:0002064 12 hyperreflexia in upper limbs 60 33 occasional (7.5%) Occasional (29-5%) HP:0007350 13 progressive pes cavus 60 33 occasional (7.5%) Occasional (29-5%) HP:0008075 14 ankle clonus 33 occasional[malacards.org]
  • 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]
Lower Extremity Spasticity
  • 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]
  • All forms of HSP, complicated and uncomplicated, share the primary symptom of lower-extremity spastic weakness.[invitae.com]
  • “Complicated” HSP is the diagnosis given to an individual who suffers with lower extremity spasticity along with such neurological problems as peripheral neuropathy, seizures, ataxia, optic neuropathy, retinopathy, dementia, mental retardation, and deafness[medschool.lsuhsc.edu]
  • The following individuals are candidates for spastic paraplegia-related gene testing: Individuals with a family history of hereditary spastic paraplegia and presentation of lower extremity spasticity and weakness and other common symptoms Individuals[centogene.com]
Babinski Sign
  • HPO Frequency Orphanet Frequency HPO Source Accession 1 degeneration of the lateral corticospinal tracts 60 33 hallmark (90%) Very frequent (99-80%) HP:0002314 2 progressive spastic paraplegia 60 33 hallmark (90%) Very frequent (99-80%) HP:0007020 3 babinski[malacards.org]
  • 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]
  • Pedigree number Gender Age at examination (years) Onset of symptoms  (years) SPRS SARA INAS Hyperreflexia UL/LL Babinski sign Clonus Decreased vibration sense Bladder disturbances Degree of disability MMSE Other signs PED1/II-1 proband M 56 40 24/52[omicsonline.org]
Sleep Disturbance
  • Roos, Indiana University · Sleep Disturbances-Mark Dyken, University of Iowa · Substance Abuse and Toxicology Disorders-Barry E. Kosofsky, Weill-Cornell University Medical Center · Neurologic Manifestations of Medical Disorders-John C.[books.google.de]
  • The patient complained of sleep disturbances only. His parents are nonconsanguineous and he has no siblings. The family history was negative for congenital malformations, dysmorphic features, and neurological and behavioural disturbances.[omicsonline.org]

Workup

  • Given these findings, along with prior negative workup, a neurology consult was obtained, and the patient was diagnosed with HSAN. The blisters were unroofed, and local wound care resulted in ultimate improvement of these lesions ( Figure 2 ).[avensonline.org]
  • 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

  • Adams, Ali Fatemi Oxford University Press, 2016 - 1398 Seiten 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.de]
  • 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]
  • Treatment Treatment Options: No treatment has been reported.[disorders.eyes.arizona.edu]
  • 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]
  • The disease has a fairly good prognosis, but the prominent weakness and spasticity may cause disability later in life. [6] In CMT-5 patients, NCV studies, usually, show a homogeneous reduction in NCV in the common peroneal nerve. [7] , [8] Our patient[sudanmedicalmonitor.org]
  • As there is a continual increase in WES-generated data on genetic variants, the pool of modifier genes likewise grows and diagnostic inferences will become more accurate, thus providing the grounds for a more precise prognosis.[wjgnet.com]
  • Prognosis This varies widely, but most often HSP is compatible with a normal life expectancy. The rate of progression varies considerably and is influenced by the mode of inheritance.[encyclopedia.com]

Etiology

  • Frontonasal dysplasia (median cleft face syndrome): Comments on etiology and pathogenesis. Birth Defects Original Article Series, 7 , 117–119. PubMed Google Scholar DeMeyer, W. (1967).[link.springer.com]
  • 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]
  • 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]
  • 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]
  • 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]
  • Ishiura, Yuji Takahashi, Toshihiro Hayashi, Kayoko Saito, Hirokazu Furuya, Mitsunori Watanabe, Miho Murata, Mikiya Suzuki, Akira Sugiura, Setsu Sawai, Kazumoto Shibuya, Naohisa Ueda, Yaeko Ichikawa, Ichiro Kanazawa, Jun Goto and Shoji Tsuji , Molecular epidemiology[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • Pathophysiological insights into ALS with C9ORF72 expansions. Journal of Neurology, Neurosurgery and Psychiatry, 84(8), 931-935.[sydney.edu.au]

Prevention

  • 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]
  • 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]
  • For patients with walking (gait) problems, canes, walkers, and wheelchairs will facilitate mobility and help to prevent falling and subsequent injury. A number of drugs are available to reduce some of the symptoms of HSP.[medschool.lsuhsc.edu]
  • Supportive care includes physical therapy, which helps to improve muscle strength, range of motion, prevent contractures of joints, and bedsores.[encyclopedia.com]
  • Prevention of secondary complications: Bladder function should be routinely monitored to avoid urinary tract infections.[ncbi.nlm.nih.gov]

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