Symptoma

Autosomal Recessive Spastic Paraplegia Type 56

SPG56

Each entry follows a 5 section structure that will cover (1) essential features of the disorder (2) physiological basis of the disorder (3) neuropsychological and other clinical presentation (4) assessment and diagnostic practices (5) evidence-based treatments [books.google.com]

Autosomal recessive spastic paraplegia type 18 (SPG18) is a rare, complex type of HSP that presents in early childhood. [cags.org.ae]

Muscle weakness when present is seen in iliopsoas, tibialis anterior and, to a lesser extent, the hamstrings. [jnnp.bmj.com]

Asymptomatic patients are also present. [emedicine.medscape.com]

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]

  • Muscle Weakness

    Abstract Hereditary spastic paraplegia (HSP) is a neurological disorder characterized by a progressive spasticity and muscle weakness of the lower limbs. It is divided into two subtypes, uncomplicated and complicated forms. [nature.com]

    Type II was defined as having late onset (older than 35 years), with rapidly developing symptoms and muscle weakness that was more prominent than spasticity. [medlink.com]

    Like all hereditary spastic paraplegias, spastic paraplegia type 4 involves spasticity of the leg muscles and muscle weakness. [ghr.nlm.nih.gov]

    Nonetheless, not all patients reach an apparent “leveling off” or functional plateau but instead experience continuous worsening of walking ability due to very slowly progressive muscle weakness and tightness. [rarediseases.org]

  • Visual Impairment

    Accompanying clinical features include intellectual disability, dystonia, cerebellar ataxia, subclinical peripheral neuropathy, visual impairment, as well as abnormalities in brain magnetic resonance imaging. [nature.com]

    Additional features include cerebellar ataxia, peripheral neuropathy, amyotrophy, extrapyramidal symptoms, cognitive impairment, deafness and visual impairment [1]. [journals.plos.org]

  • Encephalopathy

    De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nat. Genet. 45, 445–449 (2013). 10. Salinas, S., Proukakis, C., Crosby, A. & Warner, T. T. [nature.com]

    The KCNA2 gene was previously identified in patients with epileptic encephalopathies. [epilepsygenetics.net]

    […] of childhood Familial acute necrotizing encephalopathy Generalized congenital lipodystrophy with myopathy Congenital myopathy with excess of thin filaments Idiopathic pulmonary fibrosis Intermediate nemaline myopathy Severe congenital nemaline myopathy [csbg.cnb.csic.es]

    Charcot-Marie-Tooth Disease Familial Cervical Artery Dissection Gitelman Syndrome Glut1 Deficiency Syndrome 1 Ichthyosis, Congenital, Autosomal Recessive 2 Inhalational Botulism Mitochondrial DNA Depletion Syndrome 4A (Alpers Type) Pineoblastoma Steroid-Responsive Encephalopathy [familydiagnosis.com]

    3A AD 37 ATP2B4 108732 0 BICD2 609797 autosomal dominant lower extremity-predominant spinal muscular atrophy type 2 AD 13 BSCL2 606158 Lipodystrophy, congenital generalized, type 2; spastic paraplegia 17; Neuropathy, distal hereditary motor, type V; Encephalopathy [centogene.com]

  • Babinski Sign

    Affiliated tissues include globus pallidus, and related phenotypes are lower limb hyperreflexia and babinski sign Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the CYP2U1 gene on chromosome 4q25. [malacards.org]

    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]

    III-1 III-3 Age at examination 63 53 Onset 58 48 Leg spasticity Limb ataxia Thigh muscle atrophy Patellar Tendon Reflex (PTR) Achilles Tendon Reflex (ATR) Babinski sign Vibration sense Normal Normal Sphincter involvement Mini-Mental State Examination [intechopen.com]

    Primary lateral sclerosis The age of onset for primary lateral sclerosis (PLS) is usually between 40 and 60 years, with spasticity in the legs accompanied by hyperactive deep tendon reflexes, clonus, and Babinski sign. [emedicine.medscape.com]

Diagnostic workup may be complicated, as SOX10 mutations can present in a mosaic state, with a mild clinical manifestation. SOURCE: Neurol Genet. 2017 May 15;3(3):e151. doi: 10.1212/NXG.0000000000000151. eCollection 2017 Jun. [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]

[…] disorders across the lifespan (pediatric, adult, and geriatric populations) Includes interventions and methods of treatment for the outcomes patients may experience [books.google.com]

For people with HSP who experience bladder control issues, treatment with oxybutynin might help to relieve bladder spasticity. [disabled-world.com]

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]

Gene Tests for HSP As genes are discovered and assays are developed, Athena Diagnostics brings you additional tests to detect genetic forms of HSP, rule out other significant causes of spastic paraplegia including ALS and guide optimal treatment for the [1pdf.net]

• Treatment is largely supportive with the hope that increasing knowledge regarding the genetics and pathogenesis of these disorders will translate into effective therapeutic strategies. [medlink.com]

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]

This distinction is important for genetic counseling of family members and for the patient’s prognosis, in that HSP generally carries a more favorable prognosis. [2] Other components of the differential diagnosis of HSP are similar to those of PLS. [emedicine.medscape.com]

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]

[…] inversely correlated with quality of life in a previous study. 31 As the majority of patients in our cohort who met the clinical criteria for HSP did not have a genetic diagnosis, this illustrates the need for studies of clinical parameters which influence prognosis [ng.neurology.org]

Risch N et al. (1999) A genomic screen of autism: evidence for a multilocus etiology. [ ] 26. [moldiag.com]

Primary lateral sclerosis The etiology of primary lateral sclerosis (PLS) is unknown, but it may be similar to that proposed for ALS. [emedicine.medscape.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]

Through the past 15 years, significant progress has been made in improving our understanding of the genetic etiology of the ARCA. [wjgnet.com]

MtDNA defects of either primary or secondary etiology are known to segregate predominantly in clinically affected tissues. [journals.plos.org]

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]

Consequently, they are often approached together in epidemiological studies. [karger.com]

Relevant External Links for CYP2U1 Genetic Association Database (GAD) CYP2U1 Human Genome Epidemiology (HuGE) Navigator CYP2U1 Atlas of Genetics and Cytogenetics in Oncology and Haematology: CYP2U1 No data available for Genatlas for CYP2U1 Gene CYP2U1 [genecards.org]

Genetic epidemiology of autosomal recessive spastic ataxia of Charlevoix-Saguenay in northeastern Quebec. Genet Epidemiol. 1993 ; 10 : 17 – 25. 27. Hara, K, Onodera, O, Endo, M, Kondo, H, Shiota, H, Miki, K, et al. [cambridge.org]

Jorde LB et al. (1990) The UCLA-University of Utah epidemiologic survey of autism: genealogical analysis of familial aggregation. [ ] 6. Abramson RK et al. (1989) Elevated blood serotonin in autistic probands and their first-degree relatives. [ ] 7. [moldiag.com]

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]

Koenig[ 10 ] proposed a classification of ARCA based on topographical and pathophysiological criteria, while in the next year the group of Filla proposed a pathogenic classification of the hereditary ataxias[ 11 ]. [wjgnet.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]

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]

Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology. [karger.com]