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

Acronym SPG49 Keywords Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. [uniprot.org]

When present, weakness does not affect all leg muscles, but rather is most obvious in muscles of hip flexion (iliopsoas), hip abduction (gluteus medius), knee flexion (hamstrings), and foot dorsiflexsion (bending the foot back toward the shin via tibialis [rarediseases.org]

Therefore, we present non-adjusted prevalence rates in order to increase comparability between studies. [karger.com]

Phenotypic homogeneity of the Huntington disease-like presentation in a SCA17 family. Neurology 2006;67(9):1701-3. Schneider SA, Walker RH, Bhatia KP. [books.google.com]

• Short Stature

  […] of Dental Crowding : 15q Overgrowth Syndrome 2q32q33 Microdeletion Syndrome 3Mc Syndrome 1 3q29 Microdeletion Syndrome Achondroplasia Acrocephalopolysyndactyly Type III Alpha-Thalassemia / Mental Retardation Syndrome, Chromosome 16-Related Asymmetric Short [familydiagnosis.com]

  stature and fibular hypoplasia Gay Feinmesser Cohen syndrome Lipoic acid synthetase deficiency Saito Kuba Tsuruta syndrome PARC syndrome Bone dysplasia lethal Holmgren type Glaucoma, Ectopia, Microspherophakia, Stiff joints and Short stature syndrome [checkrare.com]

  He manifests a short stature and mild macrocephalus. Initially, gait disturbance in the patient was noted by his younger brother. Seven years later, maximum walking distance with assistance was about 300-500 meter. By now, he is wheelchair-bound. [omicsonline.org]

  This HSP is characterized by early onset of spastic paraplegia, motor development delaying, mental retardation, dysmorphic features (short stature, round face, low anterior hairline, dental crowding, short broad neck, mild brachycephalic microcephaly, [intechopen.com]

  Symptoms vary from person to person but typically include delayed walking, balance problems, muscle stiffness (spasticity) and weakness in the legs, developmental delay with intellectual disability, distinct facial features, and short stature. [natera.com]

• Movement Disorder

  She has always had a great interest in movement disorders with focus on movement disorder genetics and electrophysiology. She holds a Ph.D. degree in neurosciences from University College London. [books.google.com]

  Movement Disord 2016; 31: S227-S. [hih-tuebingen.de]

  Movement Disorders, 27(4), 587-588. [More Information] Shahrizaila, N., Goh, K., Ahmad-Annuar, A., Chaudhry, R., Nicholson, G., Kennerson, M., Ly, C., Ryan, M. (2012). A family with 2 X-linked disorders: Charcot-Marie-Tooth disease and hemophilia A. [sydney.edu.au]

  Movement Disorders. 2008;23(2):228-33. ^ de Niet M, de Bot ST, van de Warrenburg BP, Weerdesteyn V, Geurts AC. [en.wikipedia.org]

• Lymphedema

  SPG56 ✓ ✓ CYP7B1 SPG5 ✓ ✓ ✓ DDHD1 SPG28 ✓ ✓ ✓ DDHD2 SPG54 ✓ ✓ ENTPD1 * SPG64 ✓ ✓ ERLIN1 * SPG62 ✓ ✓ ERLIN2 SPG18 ✓ ✓ EXOSC3 * ✓ ✓ pontocerebellar hypoplasia, type 1B FA2H SPG35 ✓ ✓ GBA2 SPG46 ✓ ✓ GJC2 SPG44 ✓ ✓ hypomyelinating leukodystrophy; hereditary lymphedema [invitae.com]

  Exstrophy of the bladder Familial hemiplegic migraine type 2 Spondyloepimetaphyseal dysplasia with hypotrichosis Maxillonasal dysplasia, Binder type Osteopetrosis Albinism ocular late onset sensorineural deafness Gastroschisis Lipedema Hypotrichosis-lymphedema-telangiectasia [checkrare.com]

  GBA2 Cerebellar ataxia with spasticity AR 11 22 GBE1 Glycogen storage disease AR 36 70 GCH1 Dopa-Responsive Dystonia Hyperphenylalaninemia, BH4-deficient, GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia AD/AR 48 240 GJC2 Spastic paraplegia, Lymphedema [blueprintgenetics.com]

• Hoarseness

  […] disease Ataxia-oculomotor apraxia type 1 49,XXXXX syndrome Bardet-Biedl syndrome Radial hypoplasia, triphalangeal thumbs and hypospadias Limb-girdle muscular dystrophy Intestinal atresia multiple Autosomal recessive Charcot-Marie-Tooth disease with hoarseness [checkrare.com]

• Heart Disease

  Disease Syndrome Potocki-Lupski Syndrome Robinow Syndrome, Autosomal Dominant Robinow Syndrome, Autosomal Dominant 2 Robinow Syndrome, Autosomal Recessive Rubinstein-Taybi Syndrome 1 Ruvalcaba Syndrome Seckel Syndrome 1 Short Stature-Valvular Heart Disease-Characteristic [familydiagnosis.com]

  Your recognised location is United States (US) Coronary heart disease This article is freely available only to users in the UK. Your recognised location is United States (US) Melanoma This article is freely available only to users in the UK. [evidence.nhs.uk]

  Too much iron in the body causes joint pain (arthritis), liver disease, diabetes, skin discoloration, excessive tiredness, and heart disease that usually becomes severe by age 30. [natera.com]

  I25.10 - I25.9 Chronic ischemic heart disease M81.0 - M81.8 Osteoporosis without current pathological fracture Q24.8 Other specified congenital malformations of heart [Brugada syndrome] Q44.6 Cystic disease of liver Q61.11 - Q61.3 Polycystic kidney Q76.1 [aetna.com]

  […] polydactyly heart disease Amino aciduria with mental deficiency, dwarfism, muscular dystrophy, osteoporosis and acidosis Refsum disease Spastic paraplegia 25 Camptodactyly-ichthyosis syndrome BRCA1 hereditary breast and ovarian cancer syndrome Multicentric [checkrare.com]

• Vascular Disease

  Other conditions, specifically Meniere's disease and structural and vascular brainstem disease, must be excluded (Black, 2006). [aetna.com]

• Suggestibility

  […] below. 9 Further subdivision of pure HSP was also suggested by Harding based on the age of onset of the disease. [jnnp.bmj.com]

  In addition, a missense mutation in exon 10 resulted in predominant optical nerve atrophy, which might suggest deleterious interactions of this SPG7 variant with its substrate OPA1, the mutated gene product in optic atrophy type 1. [hspersunite.org.au]

  With exception of few missense mutations all mutations cause a premature truncation of the protein suggesting “loss of function” as the likely pathogenic mechanism. [omicsonline.org]

  A study by Agosta et al suggested that the various neurologic disorders designated as HSP share a common neurodegenerative cascade. [emedicine.medscape.com]

  Preliminary results suggest that the STCH 3’UTR single nucleotide substitution significantly affects the luciferase activity. [research.unipd.it]

• Round Face

  This HSP is characterized by early onset of spastic paraplegia, motor development delaying, mental retardation, dysmorphic features (short stature, round face, low anterior hairline, dental crowding, short broad neck, mild brachycephalic microcephaly, [intechopen.com]

• Dystonia

  She has received many awards, among others the European Dystonia Society David Marsden Award and the AAN Jon Stolk Award in Movement Disorders for Young Investigators. [books.google.com]

  Other disease features encountered in this cohort included cervical dystonia, vertical gaze palsy, ptosis and severe intellectual disability. [hspersunite.org.au]

  […] syndrome Wolf-Hirschhorn syndrome Intellectual disability - hypoplastic corpus callosum - preauricular tag Osteogenesis imperfecta type II Achalasia microcephaly syndrome Adrenomyodystrophy Orofaciodigital syndrome 3 Stiff person syndrome Myoclonus-dystonia [checkrare.com]

  Hyperphenylalaninemia, BH4-deficient, GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia AD/AR 48 240 GJC2 Spastic paraplegia, Lymphedema, hereditary, Leukodystrophy, hypomyelinating AD/AR 26 57 HACE1 Spastic paraplegia and psychomotor retardation [blueprintgenetics.com]

  Spartin Complex Early childhood Yes – Mental retardation, shortness of stature SPG21 ( Simpson et al ., 2003 ) 15q21–q22 Maspardin Complex 20–40 Yes Yes Extrapyramidal syndrome, dementia, thin CC, periventricular white matter hyperintensities, cataract, dystonia [academic.oup.com]

• Spastic Gait

  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]

  SPG7 mutations are a frequent cause of middle-aged onset of spastic gait when strict inclusion criteria are applied and should, therefore, be tested in autosomal recessive or sporadic hereditary spastic paraplegia. [antikoerper-online.de]

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

• Tremor

  13q14 – Pure 1 No – – SPG25 ( Zortea et al ., 2002 ) 6q23-q24.1 – Complex 30–46 No Yes Multiple disc herniation, bilateral cataract, congenital glaucoma SPG26 ( Wilkinson et al ., 2005 ) 12p11.1–12q14 – Complex 22–42 No Yes Emotional lability, tongue tremor [academic.oup.com]

  Only one of five patients with hereditary spastic paraplegia showed clinical indication of extrapyramidal involvement in the form of subtle bradykinesia and slight resting tremor. [intechopen.com]

  Other symptoms may also occur including muscle weakness, delayed motor skills, and involuntary movements such as tremors. [natera.com]

  Myopathy- Abnormal Genitalia Syndrome X,XR,G 99.98 NA of NA MUSK Fetal Akinesia Deformation Sequence, Congenital Myasthenic Syndrome AR 95.58 23 of 25 MYBPC1 Distal Arthrogryposis Type 1b, Lethal Congenital Contracture Syndrome, Congenital Myopathy With Tremor [igenomix.es]

  Genetics of essential tremor: Meta-analysis and review. Neurology. 2014;82(11):1000-1007. Taylor RW, Pyle A, Griffin H, et al. [aetna.com]

• Cerebellar Sign

  Although spastic paraparesis is clearly the major sign in SPG30, superficial examination could miss the associated neurological signs (e.g. cerebellar signs) leading to the initial diagnosis of pure and not complicated HSP. [academic.oup.com]

  Cerebellar signs were present in 4 patients (family I) and consisted of a dysarthric cerebellar speech, dysmetria, and abnormal rapid alternating movements in the upper extremities. [ajnr.org]

  A trace of terminal dysmetria may also be found in the upper limbs, but more florid cerebellar signs are not seen. [jnnp.bmj.com]

  There were subtle cerebellar signs in the upper limbs and mild cerebellar dysarthria. Ophthalmological examination showed normal retinal and macular findings, but visual acuity was 0.3–0.5. [journals.plos.org]

• Dysmetria

  Cerebellar signs were present in 4 patients (family I) and consisted of a dysarthric cerebellar speech, dysmetria, and abnormal rapid alternating movements in the upper extremities. [ajnr.org]

  A trace of terminal dysmetria may also be found in the upper limbs, but more florid cerebellar signs are not seen. [jnnp.bmj.com]

  Moderate truncal ataxia was present with bilateral dysmetria and dysdiadochokinesia. It was not possible to assess cerebellar function in the legs due to weakness. [journals.plos.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]

Lifelong treatment with biotin supplementation can prevent the symptoms from occurring. With early diagnosis and treatment with biotin, people with Holocarboxylase Synthetase Deficiency can live healthy lives. [natera.com]

HSP cannot be prevented, slowed or reversed, but treatments can relieve some of the symptoms and help the person manage day-to-day activities. [campbellspharmacy.co.uk]

Upon obtaining the gene test results, it is possible to apply specific treatment, to perform screening for the mutations within family or population of affected patients, and in general, to improve patient’s quality of life. [ncbi.nlm.nih.gov]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice . [uniprot.org]

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]

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]

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]

The presence of syndactyly seems to represent a different genetic variant of LQTS also associated with a poor prognosis. [aetna.com]

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]

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]

Candidates for diagnostic testing include infants, children, and adults with generalized hypotonia and proximal muscle weakness of unknown etiology. [aetna.com]

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]

Epidemiology The prevalence of HSP varies in different studies. Such variation is probably due to a combination of differing diagnostic criteria, variable epidemiological methodology, and geographical factors. [jnnp.bmj.com]

The majority of individuals with HSP have a normal life expectancy. [16] Epidemiology [ edit ] Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. [34] A Norwegian study of more than 2.5 [en.wikipedia.org]

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]

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

HSP cannot be prevented, slowed or reversed, but treatments can relieve some of the symptoms and help the person manage day-to-day activities. [campbellspharmacy.co.uk]

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]

While pharmacotherapies have made some impact on the prevention of SCD, the introduction of implantable cardioverter-defibrillator (ICD) therapy has been the single major advance in the prevention of SCD in the young. [aetna.com]