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]

CASE PRESENTATION: We describe a Chinese family with ARHSP-TCC. Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. [hspersunite.org.au]

If the production of the normal or the abnormal transcript were gender dependent, it might provide an explanation for the sex difference observed in the present family. [jmg.bmj.com]

A 19-year-old young man, born out of a nonconsanguineous marriage, presented with a history of progressive difficulty in walking for the past 3 years. [neurologyindia.com]

Hypogonadotropic hypogonadism usually presenting in the first two decades of life Common, but less frequent features: Anterior hypopituitarism. [ncbi.nlm.nih.gov]

• Developmental Delay

  delay Blood: Creatine kinase ⇑ SIL1 (608005) SIL1 NPC (257220) 2–30 y Supranuclear ophthalmoplegia, splenomegaly, dystonia, cognitive deficits Leucocytes and/or fibroblasts: Chitotriosidase⇑ Oxysterol ⇑ Skin biopsy: Filipin test NPC1/NPC2 (607623/601015 [neupsykey.com]

  delay, learning disorders, speech difficulties (dysarthria), and mood swings. [flybase.org]

  Delay, Digitotalar Dysmorphism, Freeman-Sheldon Syndrome, Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome, Sheldon-Hall Syndrome AD,AR 99.97 69 of 69 NEB Nemaline Myopathy, Childhood-Onset Nemaline Myopathy, Distal Nebulin Myopathy AR 86.77 [igenomix.es]

  Congenital hypothyroidism and growth hormone deficiency can result in global developmental delay, severe cognitive impairment, and short stature. [ncbi.nlm.nih.gov]

• Anemia

  […] cell carcinoma Pelizaeus-Merzbacher-like due to HSPD1 mutation Persistent polyclonal B-cell lymphocytosis Peutz-Jeghers syndrome Piebaldism Primary peritoneal carcinoma Pseudohyperaldosteronism type 2 Renal pseudohypoaldosteronism type 1 Retinopathy - anemia [csbg.cnb.csic.es]

  […] cognitive deficits Leucocytes and/or fibroblasts: Chitotriosidase⇑ Oxysterol ⇑ Skin biopsy: Filipin test NPC1/NPC2 (607623/601015) NPC1/NPC2 Wilson disease (277900) 5–35 y Hepatopathy, dystonia, tremor, parkinsonism, Kayser–Fleischer rings, hemolytic anemia [neupsykey.com]

  Myopathy, Autosomal Dominant Centronuclear Myopathy AR 100 20 of 20 C12ORF65 Combined Oxidative Phosphorylation Deficiency, Autosomal Recessive Spastic Paraplegia AR na na CACNA1E Epileptic Encephalopathy AD 99.94 25 of 25 CASK Nonspherocytic Hemolytic Anemia [igenomix.es]

• Brachydactyly

  Detection Sanger Sequencing $1130 Sequencing with CNV PGxome $890 Primary Microcephaly, Autosomal Recessive, via WDR62 Gene Sequencing with CNV Detection Sanger Sequencing $1430 Sequencing with CNV PGxome $890 Robinow Syndrome and Autosomal Recessive Brachydactyly [preventiongenetics.com]

  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]

• Onset in Infancy or Childhood

  Marinesco-Sjögren syndrome: Marinesco-Sjögren syndrome is a rare disorder with onset in infancy or childhood. Homozygosity mapping in two large consanguineous families of Turkish and Norwegian origin mapped the disease gene on chromosome 5q31[ 45 ]. [wjgnet.com]

• Incontinence

  During follow-up, 94% developed sphincter problems, manifesting as urinary as well as fecal incontinence in 44%. Obesity was seen in 14 patients in total (78%), of whom 9 were non-ambulatory. [nature.com]

  In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. [genecards.org]

  He had symptoms of a neurogenic bladder, without incontinence. Electroencephalography (EEG), electromyography (EMG) and nerve conduction velocities (NCV) were normal. [journals.plos.org]

• Urinary Incontinence

  During follow-up, 94% developed sphincter problems, manifesting as urinary as well as fecal incontinence in 44%. Obesity was seen in 14 patients in total (78%), of whom 9 were non-ambulatory. [nature.com]

• Ataxia

  Metabolic ataxias: The subgroup of metabolic ataxias includes disorders characterized by progressive ataxia, recurrent ataxia and ataxia as a minor feature. [wjgnet.com]

  Ataxia without neuropathy ( Pure cerebellar ataxia, possibly associated with other symptoms ) ARCA1 (610743) Late onset: 32 y (17–46 y) Pure cerebellar ataxia, late onset, tendon reflexes⇑ – SYNE1 (608441) SYNE1 ARCA2 (612016) 4 y (1–11 y) Epilepsy, myoclonus [neupsykey.com]

  […] spastic ataxia of Charlevoix-Saguenay Autosomal recessive spastic ataxia of Charlevoix-Saguenay (disorder) Autosomal recessive spastic paraplegia type 11 Autosomal recessive spastic paraplegia type 11 (disorder) Autosomal recessive spastic paraplegia [medicbind.com]

• Hyperreflexia

  […] spastic paraplegia 2017 Billable/Specific Code Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by varying degrees of lower limb spasticity, pyramidal weakness, hyperreflexia [medicbind.com]

  People with spastic paraplegia type 31 can also experience progressive muscle wasting (amyotrophy) in the lower limbs, exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, reduced bladder control, and high-arched feet ( pes cavus [ghr.nlm.nih.gov]

  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]

• Babinski Sign

  Neurological examination disclosed mild spasticity and weakness in the legs, hyperreflexia in all limbs, and bilateral Babinski sign. [bmcmedgenet.biomedcentral.com]

  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 pure forms, clinical features consist of isolated pyramidal signs, such as brisk reflexes, Babinski sign, spasticity and motor deficit, which can be associated with sphincter disturbances and deep sensory loss. [academic.oup.com]

• Abnormal Gait

  Many mutated genes are linked to abnormal lipid metabolism. [en.wikipedia.org]

  […] examination, and (4) definitely affected with abnormal gait and neurological examination. [jmg.bmj.com]

• Akinesia

  Neurogenetic fetal akinesia and arthrogryposis: genetics, expanding genotype-phenotypes and functional genomics. Journal of medical genetics, jmedgenet-2020-106901. [igenomix.es]

  […] disease Partial androgen insensitivity syndrome Progressive supranuclear palsy - corticobasal syndrome Progressive supranuclear palsy - parkinsonism Progressive supranuclear palsy - progressive non fluent aphasia Progressive supranuclear palsy - pure akinesia [csbg.cnb.csic.es]

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]

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]

Fatemi Oxford University Press, ١٨‏/٠٨‏/٢٠١٦ - 1488 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]

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]

Effects of intensive voice treatment (the Lee Silverman Voice Treatment [LSVT]) on ataxic dysarthria: a case study. [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: 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]

[…] 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]

Accordingly, plasma oxysterols are biomarkers that should be included in the screening of any spastic paraplegia of unknown etiology. [oxfordmedicine.com]

Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies. Hum Mol Genet. PubMed PMID: 24973356 Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer's disease. N Engl J Med. [books.google.com]

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

Yet, mutations in SPG4/ SPAST represent the most frequent molecular etiology in autosomal dominant (AD) patients and sporadic cases. [bmcmedgenet.biomedcentral.com]

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]

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]

[…] hormone deficiency with ataxia Classification (Orphanet): - Rare endocrine disease - Rare genetic disease - Rare gynecologic or obstetric disease - Rare infertility - Rare neurologic disease Classification (ICD10): - Diseases of the nervous system - Epidemiological [csbg.cnb.csic.es]

Ruano L, Melo C, Silva MC, Coutinho P: The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 2014;42:174-183. [karger.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]

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]

This is the first step towards the identification of a new gene crucial for understanding the underlying pathophysiology of HSP. [academic.oup.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]

Prevention of Secondary Complications Daily physical therapy is recommended to maintain and improve coordination, muscle strength, and gait; reduce spasticity; and prevent contractures. [ncbi.nlm.nih.gov]