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]

• Asymptomatic

  The father, brother, and uncle were both asymptomatic while the grandfather was wheelchairbound and the mother had abnormal gait. [omicsonline.org]

  The phenotype was one of pure HSP with a wide range of disease severity with some patients requiring a wheelchair whereas others remained asymptomatic at the age of 40 years. [jnnp.bmj.com]

  The parents (II-1 and 2), who were first cousins, were neurologically asymptomatic. Arrow indicates the proband, and dots indicate the persons who permit analysis of their DNAs. [intechopen.com]

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

  This issue is especially relevant in studies based on genetic centre records, where clinical inclusion criteria are clearly needed to differentiate clinically affected patients from asymptomatic or presymptomatic carriers. [karger.com]

• Anemia

  […] leukemia Retinitis pigmentosa Familial prostate cancer Baraitser-Winter syndrome Acute promyelocytic leukemia Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Adrenocortical carcinoma Li-Fraumeni syndrome Papilloma of choroid plexus Fanconi anemia [csbg.cnb.csic.es]

  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]

  […] syndromes Spasticity, Childhood-onset, with Hyperglycinemia (SPAHGC) : Spastic ataxia ● Glutaredoxin 5 (GLRX5) ; 14q32.13; Recessive Epidemiology: Lebanese & Chinese families Genetics Mutations: K51del; 8-BP ins, NT82 Allelic disorder: Sideroblastic anemia [neuromuscular.wustl.edu]

  SLC19A2, SLC25A38, SLC4A1, SLX4, SPTA1, SPTB, TCN2, THBD, TMPRSS6, TPI1, TRNT1, TSR2, XRCC2, YARS2)Pan39Anemia di Diamond-Blackfan (GATA1, RPL11, RPL35A, RPL5, RPL15, RPL26, RPL27, RPS10, RPS17, RPS19, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, TSR2)Pan50 Anemia [bredagenetics.com]

• Vomiting

  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]

• 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]

  To date, treatment of HSPs is primarily directed symptomatically towards reducing muscle spasticity. [els.net]

  A recessive form of spastic paraplegia with distal muscle wasting. Arch Neurol 1967, 16 :473–485. PubMed Google Scholar 55. [link.springer.com]

• Myalgia

  Postpolio syndrome Most patients with postpolio syndrome (PPS) present with new, slowly progressive muscle weakness, frequently accompanied by muscle pain (myalgias) and fatigue, which can occur in both previously affected and unaffected muscles. [emedicine.medscape.com]

• Ectopia Lentis

  lentis and megalocornea Greenberg dysplasia Griscelli disease type 1 Griscelli disease type 3 Hamel cerebro-palato-cardiac syndrome Hereditary hypercarotenemia and vitamin A deficiency Hereditary proximal myopathy with early respiratory failure Hypocalcemic [csbg.cnb.csic.es]

• Psychomotor Retardation

  Recessive Genetics: Mutations Val61Ala Stop codon (540delG) RPIA protein Converts ribulose-5-phosphate to ribose-5-phosphate Deficiency leads to accumulation of pentoses & pentose phosphates Epidemiology: Single patient identified Onset Early childood Psychomotor [neuromuscular.wustl.edu]

  Spinocerebellar ataxia autosomal recessive type 11: A slowly progressive new type of ARCA accompanied by psychomotor retardation has been recently described in a small consanguineous Japanese family with two affected individuals and is known as spinocerebellar [wjgnet.com]

• Tremor

  […] the complex form of spastic paraplegia type 2 have lower limb spasticity and can also experience problems with movement and balance (ataxia); involuntary movements of the eyes (nystagmus); mild intellectual disability; involuntary, rhythmic shaking (tremor [ghr.nlm.nih.gov]

  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]

  R731X (Stop); Deletion KIF1C protein Axon transport, Anterograde Kinesins: Other disorders Onset Age: Range 1 to 69 years; Often 6 to 18 years Dysphagia Falling Clinical Cerebellar ataxia Dysarthria Gait disorder Nystagmus: Horizontal; Some patients Tremor [neuromuscular.wustl.edu]

  The SCA7 autosomal-dominant inheritance pattern is similar to a mutant ATXN5-induced gain in Gcn5 HAT. [9] Spinocerebellar ataxia type 15 has been classified as an ADCA Type III as it has been noted to have postural and action tremor in addition to cerebellar [en.wikipedia.org]

  Study of a family with progressive ataxia, tremor and severe distal amyotrophy. Can J Neurol Sci. 1980 ; 7 : 345 – 9. 21. Duquette, A, Roddier, K, McNabb-Baltar, J, Gosselin, I, St-Denis, A, Dicaire, MJ, et al. [cambridge.org]

• Abnormal Gait

  The father, brother, and uncle were both asymptomatic while the grandfather was wheelchairbound and the mother had abnormal gait. [omicsonline.org]

  They all presented in the first 2 years of life with developmental delay, delayed walking, abnormal gait, and mild to severe mental retardation. They also had spasticity of the lower limbs, and a very thin corpus callosum. [cags.org.ae]

  The symptoms of HSP can include the following: Abnormal gait Delayed walking Repeated tripping or falling Weakness of the leg muscles Rigidity and increased tone of the person's leg muscles People with uncomplicated HSP can also experience additional [disabled-world.com]

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

• 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 − − [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]

Autosomal dominant cerebellar ataxia Autosomal dominant is the manner in which this condition is inherited Types ADCS type1, ADCA type 2, ADCA type 3 [1] Diagnostic method MRI, CT scan [2] Treatment Anticonvulsants may be used [1] Autosomal dominant cerebellar [en.wikipedia.org]

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

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]

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]

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]

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]

9p13 SPG48 : AP5Z1; 7p22 SPG 62 : ERLIN1; 10q24 SPG 75 : MAG; 19q13 SPG 76 : CAPN1; 11q13 SPG 79 : UCHL1; 4p13 Spastic Ataxia 1, Hereditary (SPAX1) 21 ● Vesicle-related membrane protein 1 (VAMP1; Synaptobrevin; SYB1) ; Chromosome 12p13.31; Dominant Epidemiology [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]

[…] after the disease is underway. [9] There is no effective treatments that could alter the progression of this disease, therefore care is given, like occupational and physical therapy for gait dysfunction and speech therapy. [ medical citation needed ] Epidemiology [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]

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]