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]

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

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]

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]

• Anemia

  Adrenomyodystrophy Orofaciodigital syndrome 3 Stiff person syndrome Myoclonus-dystonia Sialuria, French type Hartnup disease Toriello-Carey syndrome Thompson Baraitser syndrome Periodic fever, aphthous stomatitis, pharyngitis and adenitis Sickle cell anemia [checkrare.com]

  […] two years of life and can include small head and brain (microcephaly), lack of energy, feeding problems, developmental delay, intellectual disability, seizures, vision problems, poor muscle tone (hypotonia), and large red blood cells (megaloblastic anemia [natera.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]

  […] below) Factor XIII deficiency, congenital (F13 (Factor XIII beta globulin)) Familial adenomatous polyposis coli (APC) (see below) Familial dysautonomia (IKBKAP) Familial hypocalciuric hypercalcemia (see below) Familial Mediterranean fever (MEFV) Fanconi anemia [aetna.com]

• Swelling

  Tendon Reflex (PTR) − ++ Achilles Tendon Reflex (ATR) + − − Babinski sign + + Vibration sense Normal Normal Sphincter involvement − − Mini-Mental State Examination (MMSE) 16/30 25/30 Lower limb NCV FWCV decreased Decreased Sural nerve biopsy Axonal swelling [intechopen.com]

  Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies. Journal of Neurology, Neurosurgery and Psychiatry, 68, 483-488. [More Information] [sydney.edu.au]

• Ectopia Lentis

  lentis Progressive osseous heteroplasia Yemenite deaf-blind hypopigmentation syndrome Microtia eye coloboma and imperforation of the nasolacrimal duct Multiple endocrine neoplasia type 2B Oculorenocerebellar syndrome Rhizomelic dysplasia Patterson Lowry [checkrare.com]

  Two fundamental features of the Ghent nosology are aortic root aneurysm and ectopia lentis. In the absence of a family history of Marfan syndrome, the presence of aortic root aneurysm and ectopia lentis are sufficient to diagnose Marfan syndrome. [aetna.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]

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

  […] paraplegia 7 Spastic paraplegia 26 Trichodental syndrome Spastic paraplegia 5A Wagner syndrome Spasmodic dysphonia Al Gazali syndrome Paroxysmal exertion-induced dyskinesia KCNQ2-Related Disorders Orofaciodigital syndrome 5 Polyneuropathy mental retardation [checkrare.com]

• Skin Rash

  If untreated, Holocarboxylase Synthetase Deficiency can cause delayed development, seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, movement and balance problems, skin rashes, hair loss, and yeast infections. [natera.com]

• 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]

• Spastic Paraplegia

  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]

  Keywords Hereditary Spastic Paraplegia Spastic Paraparesis Primary Lateral Sclerosis Spastic Gait Hereditary Spastic Paraparesis These keywords were added by machine and not by the authors. [link.springer.com]

  Neurology Invitae Hereditary Spastic Paraplegia Autosomal Recessive Panel Test description The Invitae Hereditary Spastic Paraplegia Autosomal Recessive Panel analyzes up to 47 genes that cause hereditary spastic paraplegia ( HSP ) that is inherited in [invitae.com]

• Seizure

  Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra [uniprot.org]

  Infants with the severe form of HHH Syndrome have episodes of low energy (lethargy), feeding problems, vomiting, seizures, and sometimes coma. [natera.com]

  Different types of seizures have sometimes been described in affected members within the same family. [jnnp.bmj.com]

  Other genetic types of HSP tend to be associated with additional symptoms (“complicated HSP”) including difficulty with coordination (“ataxia”), impaired vision, seizures (epilepsy), muscle atrophy, disturbance of the nerves in the arms and legs (neuropathy [rarediseases.org]

  […] dominant type 2 Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation Kennedy disease Optic atrophy 2 Isolated growth hormone deficiency type 1A Pseudohypoparathyroidism type 2 Prolidase deficiency Intellectual disability, epileptic seizures [checkrare.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]

• 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]