Epilepsy was present in members of three of the four generations on whom we have information. [ncbi.nlm.nih.gov]

These endogenous control centers and signaling pathways are further modified by independent genetic epigenetic, biologic, or other factors, which further increase the heterogeneity in presentation of seizures, their treatment, and their comorbidities. [books.google.de]

In 6 of 7 reported patients the presenting sign was nystagmus but one individual with reported onset of disease at age 5 years presented with ataxia. [disorders.eyes.arizona.edu]

[…] half of the patients presenting missense mutations. [jnnp.bmj.com]

A novel, 1954-bp homozygous deletion at the NT5C2 locus involving the entire coding exon 11 was identified to be present in both sequenced, affected siblings. [nature.com]

• Epilepsy

  Epilepsy was present in members of three of the four generations on whom we have information. [ncbi.nlm.nih.gov]

  Elucidation of these complex interactions and identification of biomarkers guiding therapeutic interventions will be necessary to improve our ability to treat early-life epilepsies. [books.google.de]

  Ingo Helbig is a child neurologist and epilepsy genetics researcher working at the Children’s Hospital of Philadelphia (CHOP), USA. He also leads the epilepsy genetics group at the University of Kiel, Germany. [epilepsygenetics.net]

  Abstract Objective: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. [neurology.org]

• Weakness

  The onset was limited to the first four decades of life; the symptoms were typically those of progressive weakness and spasticity of lower limbs. Epilepsy was present in members of three of the four generations on whom we have information. [ncbi.nlm.nih.gov]

  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]

  This means they have other symptoms in addition to the muscle weakness and spasticity. They may have a wide range of symptoms. [nhs.uk]

  As previously mentioned, hereditary spastic paraplegia (HSP) is not a single disease entity but a group of clinically and genetically diverse disorders that cause progressive and generally severe lower extremity weakness and spasticity. [emedicine.medscape.com]

  HSP is mainly characterized by different degrees of stiffness and weakness of the person's leg muscles and hip muscles, along with gait difficulties and issues with walking. [disabled-world.com]

• Disability

  Most affected individuals have intellectual disability that varies from mild to profound and is usually apparent by early childhood. Other neurologic findings include speech difficulties (dysarthria) and delayed speech. [secure.ssa.gov]

  All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. [neurology.org]

  People with spastic quadriparesis usually cannot walk and often have other developmental disabilities such as intellectual disability; seizures; or problems with vision, hearing, or speech. [cdc.gov]

  […] paraplegia with intellectual disability, and corpus callosum agenesis. [invitae.com]

  The mean disability score was 2.1. There is no significant difference between disability score and type of mutation. [jnnp.bmj.com]

• Difficulty Walking

  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]

  People with spastic diplegia might have difficulty walking because tight hip and leg muscles cause their legs to pull together, turn inward, and cross at the knees (also known as scissoring ). [cdc.gov]

• Failure to Thrive

  There was no history of epileptic attacks, skeletal or facial deformity, failure to thrive, and no self-mutilation or aggression. There was no increased rate of infectious diseases or any skin abnormality. [nature.com]

• Strabismus

  Strabismus and nystagmus are commonly present. Systemic Features: The facial features ae described as "fine" with a short nose and a thin upper lip. The forehead is unusually high. [disorders.eyes.arizona.edu]

  On regular ophthalmological assessment, there were no signs of strabismus or optic-nerve hypoplasia. No sensory deficits were detected in the young sisters, but these were difficult to be assess in the older ones. [bmcresnotes.biomedcentral.com]

• Muscle Spasticity

  Treatment is mainly supportive, with skeletal muscle relaxants, botulinum toxin, and physiotherapy for muscle spasticity. HSP may be nonprogressive ( childhood-onset ) or progressive ( adult-onset ). [amboss.com]

  Many symptoms that are common in people with HSP are not directly caused by HSP but are instead caused indirectly by muscle spasticity, weakness, or hyperactive reflexes. Spasticity Spasticity is an increase in muscle tone with resulting stiffness. [emedicine.medscape.com]

  One caveat however: although early childhood-onset forms of HSP may be “non-progressive”, the degree of spasticity may increase slowly if adequate range-of-motion is not maintained through stretching exercises and muscle spasticity reduction. [rarediseases.org]

  Depending on which areas of the brain are affected, one or more of the following movement disorders can occur: Stiff muscles (spasticity) Uncontrollable movements (dyskinesia) Poor balance and coordination (ataxia) There are four main types of CP: Spastic [cdc.gov]

• Muscle Spasm

  Tightness in the legs and leg muscle spasm (often at night) are not uncommon. The consequences of abnormal walking pattern cause strain on the ankles, knees, hips, and back and often cause pain in these areas. [rarediseases.org]

  These symptoms can include: Leg cramps Paresthesia Muscle spasms Highly arched feet Bladder control problems Relatively mild muscle wasting Diminished vibration sense in the feet Ankle clonus or abnormal reflex movements of the foot While it is less common [disabled-world.com]

• Spastic Paraplegia

  The concomitance of spastic paraplegia and epilepsy in several members of the same family is unlikely to be fortuitous and probably represents the pleiotropic effect of a single mutant gene. [ncbi.nlm.nih.gov]

  spastic paraplegia type 20, Spastic paraplegia 20, autosomal recessive, Cross-McKusick syndrome, Spastic paraplegia 20 [rarediseases.info.nih.gov]

  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]

  Diagnosing hereditary spastic paraplegia Hereditary spastic paraplegia is diagnosed following a thorough clinical examination and the identification of typical symptoms. [nhs.uk]

• Seizure

  Seizures are more common early in life than in adulthood. Bidirectional interactions between seizures and normal developmental processes define their expression and outcomes. Several developmentally regulated factors control neuronal excitability. [books.google.de]

  Methods: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. [neurology.org]

  Proud: microcephaly, ACC, spasticity, seizures, ataxia, genital anomalies. [pediatrics.aappublications.org]

  Seizures are treated with standard anticonvulsant medications. [secure.ssa.gov]

  A Comparison of Valproate with Carbamazepine for the Treatment of Complex Partial Seizures and Secondarily Generalized Tonic-Clonic Seizures in Adults. N Engl J Med 1992;327:765-71. [ PUBMED ] [ FULLTEXT ] 6. Harding AE. [ruralneuropractice.com]

• Lower Extremity Spasticity

  Genetic counseling Hereditary Spastic Paraplegia (HSP) is a group of clinically and genetically heterogeneous disorders characterized by lower extremity spasticity and weakness. [asperbio.com]

  Clinical Features  Symptoms depend on the type of HSP inherited  Main feature progressive spasticity in the lower limbs, due to pyramidal tract dysfunction  In the lower extremities, spasticity is increased at the hamstrings, quadriceps and ankles [slideshare.net]

  All forms of HSP, complicated and uncomplicated, share the primary symptom of lower-extremity spastic weakness. [invitae.com]

  The following individuals are candidates for spastic paraplegia-related gene testing: Individuals with a family history of hereditary spastic paraplegia and presentation of lower extremity spasticity and weakness and other common symptoms Individuals [centogene.com]

• Paresis

  Hereditary spastic paraparesis is a group of rare hereditary disorders characterized by progressive, spinal, nonsegmental, spastic leg paresis, sometimes with intellectual disability, seizures, and other extraspinal deficits. [merckmanuals.com]

  Oxidoreductase Deficiency; FALDH Deficiency; Fatty Aldehyde Dehydrogenase Deficiency; Congenital Icthyosis Mental Retardation Spasticity Syndrome; Ichthyosis Spastic Neurologic Mental Retardation Disorder; Congenital Ichthyosis Oligophrenia and Spastic Paresis [secure.ssa.gov]

  1-10 in 100,000 people worldwide have HSP  Can affect people of all ages, but average age at onset is 24 4. 1 2 3 4 • Hereditary spastic paresis • Familial spastic paraplegia • Strumpell-Lorrain disease: first described 1883-1888 • French Settlement [slideshare.net]

  Kufor-Rakeb Syndrome Clinical Characteristics Ocular Features: Most patients have a supranuclear gaze paresis. Patients later may have dystonic oculogyric spasms. [disorders.eyes.arizona.edu]

• Excitement

  Several developmentally regulated factors control neuronal excitability. GABAA receptors hold a central role as they control neuronal activity in an age-specific manner. [books.google.de]

  Other features like hypomania, a psychiatric anomaly of extreme excitement, visual impairments like strabismus or nerve optic hypoplasia, and dysarthria, a speech articulation abnormality as reported by Schuurs-Hoeijmakers et al. [ 11 ] were not observed [bmcresnotes.biomedcentral.com]

These endogenous control centers and signaling pathways are further modified by independent genetic epigenetic, biologic, or other factors, which further increase the heterogeneity in presentation of seizures, their treatment, and their comorbidities. [books.google.de]

Treatment Treatment Options: No treatment has been reported. [disorders.eyes.arizona.edu]

Learn more about screening and diagnosis Treatments and Intervention Services There is no cure for CP, but treatment can improve the lives of those who have the condition. It is important to begin a treatment program as early as possible. [cdc.gov]

Access to research treatment protocols 9. [pediatrics.aappublications.org]

Provision of prognosis or expected clinical course 3. Discussion of genetic mechanism(s) and recurrence risks 4. Refined treatment options 5. Avoidance of unnecessary or redundant diagnostic tests 6. [pediatrics.aappublications.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]

[…] biomarkers of childhood acute encephalopathy associated with infection Ministry of Education, Culture, Sports, Science and Technology: Grants-in-Aid for Scientific Research(基盤研究(C)) Project Year: 2008 - 2010 Investigator(s): Hiroyuki TORISU To improve the prognosis [researchmap.jp]

Etiology Pathophysiology Clinical features Pure HSP is characterized by an insidious onset and slow progression of the following symptoms Patients with complicated HSP have all the features of pure HSP as well as additional neurological features, such [amboss.com]

Clarification of etiology 2. Provision of prognosis or expected clinical course 3. Discussion of genetic mechanism(s) and recurrence risks 4. Refined treatment options 5. Avoidance of unnecessary or redundant diagnostic tests 6. [pediatrics.aappublications.org]

Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. Hum Mutat. 2017 Jun;38(6):621-636. [disorders.eyes.arizona.edu]

Chapters on epidemiology, embryology, non-syndromic hearing loss, and syndromic forms of hearing loss have all been updated with particular attention to the vast amount of new information on molecular mechanisms, and chapters on clinical and molecular [books.google.com]

Epidemiology References: [1] [2] [3] Epidemiological data refers to the US, unless otherwise specified. [amboss.com]

The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83. [invitae.com]

Epidemiological, clinical, and genetic landscapes of hypomyelinating leukodystrophies. J Neurol. 2014;261(4):752-8. Hobson GM, Kamholz J. PLP1-Related Disorders. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, et al., editors. [plaza.umin.ac.jp]

Suga N, Nagatoshi Y, Gondou K, Kira R, Ikuno Y, Okamura J Bone marrow transplantation 23 515-517 Mar 1999 [Refereed] Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan. [researchmap.jp]

Etiology Pathophysiology Clinical features Pure HSP is characterized by an insidious onset and slow progression of the following symptoms Patients with complicated HSP have all the features of pure HSP as well as additional neurological features, such [amboss.com]

A role for white matter abnormalities in the pathophysiology of bipolar disorder. Neurosci Biobehav Rev 2010;34:533-54. [ PUBMED ] [ FULLTEXT ] 14. Mazza M, Di Nicola M, Marca GD, Janiri L, Bria P, Mazza S. [ruralneuropractice.com]

Pathophysiology and emerging therapeutic strategies in Pelizaeus–Merzbacher disease. Expert Opinion on Orphan Drugs. 2015;3(12):1447-59. Inoue K. [plaza.umin.ac.jp]

[…] and Neurosurgery, London, UK 3 Department of Neurology and Neurosurgery, Institute of Emergency Medicine, Chisinau, Republic of Moldova 4 Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy 5 Department of Pathophysiology [jnnp.bmj.com]

The pathogenesis and pathophysiology remain to be fully clarified. To find their diagnostic markers, we delineated the clinical features of the e... [researchmap.jp]

Treating hereditary spastic paraplegia It isn't possible to prevent, slow or reverse hereditary spastic paraplegia, but some of the symptoms can be managed so that day-to-day activities become easier. [nhs.uk]

Treatment 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 26. Gen. Spas ticity Oral Agents Foc. [slideshare.net]

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]