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]

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

Hypertrophic cardiomyopathy and diabetes are common presentations of the condition. [elsevier.es]

Dysarthria and bladder dysfunction are often present. Cerebellar ataxia is common and some patients first present with this as a prominent sign in the first and second decades. [disorders.eyes.arizona.edu]

Patients with SPG3A were more likely to present at a younger age, with a mean age at symptom onset of 10.1 (SE 4.4) years ( p = 0.022) ( figure 3 ). [ng.neurology.org]

• Vomiting

  BSCL2/seipin Complicated: spastic paraplegia associated with amyotrophy of hand muscles (Silver Syndrome) SPG19 607152 (9q33-q34) Uncomplicated HSP SPG29 609727 (1p31.1-21.1) Complicated: spastic paraplegia associated with hearing impairment; persistent vomiting [mhmedical.com]

  The clinical phenotype is one of complicated HSP with the spastic paraparesis being associated with bilateral cataracts, gastroesophageal reflux with persistent vomiting, and distal amyotrophy secondary to an apparent axonal motor neuropathy. [jnnp.bmj.com]

• Brachydactyly

  It has been described in four males from one family (two brothers and two mater syndrome de maladie de Hirschsprung-brachydactylie type D SNOMEDCT-BE (type D brachydactyly). [wordscope.com]

  Brachydactyly. Branchiootorenal (BOR) syndrome. Breast cancer. Bruton agammaglobulinemia. Campomelic dysplasia. Camurati-Engelmann disease. Canavan disease. Cancer. Cancer genetics. Cardiofaciocutaneous syndrome. [cengage.com]

  Beckwith-Wiedemann- Syndrom ME030-C3 benigne hereditäre Chorea NKX2-1 Bethlem myopathy, Ullrich congenital muscular dystrophy COL6A3 Biotinidase Defizienz BTD Birt-Hogg-Dube-Syndrom FLCN Blau-Syndrom NOD2 Blepharophimose-Ptosis-Epicanthus-inversus-Syndrom FOXL2 Brachydactylie [meduniwien.ac.at]

  TRIP4 Congenital Muscular Dystrophy, Spinal Muscular Atrophy With Congenital Bone Fractures, Congenital Muscular Dystrophy-Respiratory- Skin Abnormalities- Joint Hyperlaxity Syndrome AR 99.92 3 of 3 TRPV4 Brachyrachia, Familial Digital Arthropathy- Brachydactyly [igenomix.es]

• Muscle Spasm

  Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. [genecards.org]

  Tightness in the legs and leg muscle spasm (often at night) are not uncommon. The consequences of abnormal walking pattern cause strain on the ankles, knees, hips, and back and often cause pain in these areas. [rarediseases.org]

• Hyperreflexia

  Affiliated tissues include brain, and related phenotypes are nystagmus and hyperreflexia Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the GBA2 gene on chromosome 9p. [malacards.org]

  The gait is spastic with weakness, hyperreflexia, and extensor plantar responses in the lower limbs. The upper limbs are variably involved and movements are dysmetric. Dysarthria and bladder dysfunction are often present. [disorders.eyes.arizona.edu]

  Hyperreflexia of the lower as well as the upper limbs was also observed. Brain MRI findings were similar to that of patient II3. [omicsonline.org]

  People with this form of spastic paraplegia can also experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); intellectual disability; exaggerated reflexes (hyperreflexia [ghr.nlm.nih.gov]

  […] limb muscle weakness Decreased arm strength Weak arm [ more ] 0003484 Upper limb spasticity Uncontrollable movement in upper arms 0006986 Percent of people who have these symptoms is not available through HPO Autosomal recessive inheritance 0000007 Hyperreflexia [rarediseases.info.nih.gov]

• Spastic Gait

  Table 134-1 Genetic Types of HSP (updated from Fink JK, 2011) View Table | Favorite Table | Download (.pdf) Table 134-1 Genetic Types of HSP (updated from Fink JK, 2011) Spastic Gait (SPG) Locus OMIM Number Protein (genetic locus if protein is unknown [mhmedical.com]

  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]

  0002061 Optic atrophy 0000648 Paraplegia Leg paralysis 0010550 Progressive Worsens with time 0003676 Spastic gait Spastic walk 0002064 Urinary incontinence Loss of bladder control 0000020 Showing of 36 | Last updated: 5/1/2019 Making a diagnosis for [rarediseases.info.nih.gov]

  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]

  Hereditary spastic paraplegia ( HSP ) is a group of inherited diseases whose main feature is a progressive gait disorder. [en.wikipedia.org]

• Lower Extremity Spasticity

  HSP clinical syndromes may be limited to difficulty walking due to lower extremity spastic weakness (“uncomplicated HSP”) or may include other neurologic or systemic disturbances (“complicated HSP”). [mhmedical.com]

  […] to slowly progressive lower extremity spasticity and weakness. [research.unipd.it]

  All forms of HSP, complicated and uncomplicated, share the primary symptom of lower-extremity spastic weakness. [invitae.com]

  Non-syndromic spastic paraplegias are characterized by slowly progressive spasticity and weakness of the lower extremity, often associated with hypertonic urinary disturbances, mild reduction of lower extremity vibration sense and, occasionally, of joint [blueprintgenetics.com]

  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

  Showing of 36 | 80%-99% of people have these symptoms Babinski sign 0003487 Impaired vibratory sensation Decreased vibration sense Decreased vibratory sense Diminished vibratory sense Impaired vibratory sense [ more ] 0002495 Lower limb muscle weakness [rarediseases.info.nih.gov]

  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]

  Detailed neurological examination showed predominantly bilateral proximal pronounced paresis (3/4) of the lower limbs with hyperreflexia and positive bilateral Babinski sign. He also complains about urinary urgency. [omicsonline.org]

  In some cases of late-onset ARSACS, pyramidal signs are less severe and patients display hearing loss. [elsevier.es]

• Spastic Paralysis

  Spastic paralysis AR 33 68 AP4B1 Spastic paraplegia 47, autosomal recessive AR 17 18 AP4E1 Stuttering, familial persistent, 1, Spastic paraplegia 51, autosomal recessive AR 7 15 AP4M1 Spastic paraplegia 50, autosomal recessive AR 16 13 AP4S1 * Spastic [blueprintgenetics.com]

  Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++) ALS2 606352 amyotrophic lateral sclerosis 2; Spastic paralysis, infantile onset ascending AR 20 AMPD2 102771 pontocerebellar hypoplasia 9 AR 7 AP4B1 607245 [centogene.com]

  Infantile ascending hereditary spastic paralysis (IAHSP): clinical features in 11 families. Neurology 2003 ; 60 : 674 –82 Marti-Fabregas J, Pujol J. [ajnr.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 Treatment Options: No effective treatment is known for the neurological deficits but cataract surgery may be beneficial for visually significant cataracts. [disorders.eyes.arizona.edu]

Ali Fatemi Oxford University Press, 2016 - 1398 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]

PROGNOSIS: Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. [ncbi.nlm.nih.gov]

Abstract Although SPG11 is the most common complicated hereditary spastic paraplegia, our knowledge of the long-term prognosis and life expectancy is limited. [nature.com]

Prognosis — probable outcome of the disease. Resources — bibliographies or contact information are provided for books, Web sites, national organizations and support groups. Symptoms — physical and mental signs of the disorder. [cengage.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]

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

Arthrogryposis (multiple congenital contractures): Diagnostic approach to etiology, classification, genetics, and general principles. European Journal of Medical Genetics, 57(8), 464-472. doi:10.1016/j.ejmg.2014.03.008 Request Information [igenomix.es]

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

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

EPIDEMIOLOGY: The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. [ncbi.nlm.nih.gov]

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]

The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83. [invitae.com]

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]

MANAGEMENT: To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. [ncbi.nlm.nih.gov]

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]

Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption. Neuropsychopharmacology 39, 981–988. Petit, E., Mougin, F., Bourdin, H., Tio, G., and Haffen, E. (2014). [neurosciences.univ-fcomte.fr]

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]