Presentation
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]
Entire Body System
- Weakness
Although the disorder is typically referred to as hereditary spastic paraplegia the degree of weakness is variable and ranges from no weakness (full strength) to marked weakness (paraplegia). [rarediseases.org]
Lower extremity weakness Lower limb weakness Muscle weakness in lower limbs [ more ] 0007340 Spastic paraplegia 0001258 30%-79% of people have these symptoms Abnormal cerebellum morphology Cerebellar abnormality Cerebellar abnormalities Abnormality of [rarediseases.info.nih.gov]
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]
2005, Vol.11, No.3 doi: 10.1212/01.CON.0000293721.86238.6a Article Article Related Links Abstract Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of motor disorders characterized by bilateral leg spasticity and weakness [journals.lww.com]
Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. [genecards.org]
- Disability
For a subset of patients (n = 65), disability was evaluated using the SPATAX-EUROSPA disability score, ranging from 0 (no disability) to 7 (severe disability/confined to bed). [ng.neurology.org]
Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life. [en.wikipedia.org]
There may be wide variability in age-of-symptom onset, rate of worsening, degree of disability, and presence (and severity) of additional of neurologic involvement both within and between different genetic types of HSP. [mhmedical.com]
Individuals with complicated HSP exhibit additional neurologic features such as intellectual disability, seizures, ataxia, peripheral neuropathy, deafness, cataracts, retinal degeneration, or muscle atrophy, depending on which gene is causative. [invitae.com]
- Developmental Disorder
Diseases-Merit Cudkowicz, Massachusetts General Hospital - Paroxysmal Disorders-Solomon Moshe, Albert Einstein College of Medicine - Pediatric Neurology and Developmental Disorders-Tanjala Gipson and Deepa Menon, Kennedy Krieger Institute and Johns Hopkins [books.google.com]
Burd L et al. (1985) Inquiry into the incidence of hyperlexia in a statewide population of children with pervasive developmental disorder. [^] 13. [moldiag.com]
Gastrointestinal
- 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]
Musculoskeletal
- Muscle Spasticity
Spasticity primarily affects muscles of leg extension (quadriceps), knee flexion (hamstrings), hip adduction (bringing the knees together, thigh adductor muscles), and muscles that extend the feet (gastrocnemius-soleus [Achilles tendon]). [rarediseases.org]
A recessive form of spastic paraplegia with distal muscle wasting. Arch Neurol 1967, 16 :473–485. PubMed Google Scholar 55. [link.springer.com]
- Leg Weakness
The primary symptom of HSP is difficulty walking due to weakness and tightness (spasticity) in the legs. Both legs are affected, usually to a relatively similar degree. The term “paraplegia” means severe weakness in both legs including paralysis. [rarediseases.org]
Neurologic
- Spastic Paraplegia
OMIM : 57 Autosomal recessive spastic paraplegia-46 (SPG46) is a neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. [malacards.org]
Company Science NGS Panel – Genetic Testing for Spastic Paraplegia Hereditary Spastic Paraplegia (HSP), Spastic paraplegia, SPG, Familial Spastic Paraplegia, Hereditary Spastic Paraparesis, Strumpell-Lorrain Syndrome Hereditary Spastic Paraplegia (HSP [centogene.com]
paraplegia 42, autosomal dominant AD/AR 6 7 SPAST Spastic paraplegia AD 193 723 SPG11 Spastic paraplegia, Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease AR 162 274 SPG20 Spastic paraplegia (Troyer syndrome) AR 9 7 SPG7 Spastic paraplegia [blueprintgenetics.com]
Spastic paraplegia type 11 is a complex hereditary spastic paraplegia. Like all hereditary spastic paraplegias, spastic paraplegia type 11 involves spasticity of the leg muscles and muscle weakness. [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]
- Ataxia
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]
Friedreich ataxia was the most frequent AR-HCA, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia. [karger.com]
Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity. Am J Hum Genet. 2013 Feb 7;92(2):245-51. PubMed PMID: 23332917. [disorders.eyes.arizona.edu]
(SCAs), Friedreich ataxia, spastic ataxia of Charlevoix-Saguenay, etc. [centogene.com]
[…] by Boukhris et al., 2010 and Martin et al., 2013). (614409) MalaCards based summary : Spastic Paraplegia 46, Autosomal Recessive, also known as spg46, is related to hereditary spastic paraplegia and paraplegia, and has symptoms including cerebellar ataxia [malacards.org]
- Cerebellar Ataxia
Mutations in GBA2 cause autosomal-recessive cerebellar ataxia with spasticity. Am J Hum Genet. 2013 Feb 7;92(2):245-51. PubMed PMID: 23332917. [disorders.eyes.arizona.edu]
Recessive, also known as spg46, is related to hereditary spastic paraplegia and paraplegia, and has symptoms including cerebellar ataxia and abnormal pyramidal signs. [malacards.org]
Palau F, Espinós C: Autosomal recessive cerebellar ataxias. Orphanet J Rare Dis 2006;1:47. le Ber I, Brice A, Dürr A: New autosomal recessive cerebellar ataxias with oculomotor apraxia. Curr Neurol Neurosci Rep 2005;5: 411-417. [karger.com]
The term spinocerebellar ataxia is used to describe progressive ataxias following an autosomal dominant inheritance pattern, whereas recessive ataxias characterised mainly by cerebellar atrophy are referred to as autosomal recessive cerebellar ataxias [elsevier.es]
- 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]
Workup
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 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
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]
Etiology
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]
Epidemiology
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
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
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]