Presentation
Neuromuscular syndromes are presented clinically either as a case study or as an overview from the literature, accompanied by text presenting molecular defects, and differential diagnosis. [books.google.de]
Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromusc Disord. 2003;13:133–42. PubMed CrossRef Google Scholar 5. [link.springer.com]
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]
Entire Body System
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Progressive Ophthalmoplegia
ophthalmoplegia Homonymous hemianopia Micrognathia Abnormal facial shape Feeding difficulties Delayed speech and language development Myopia Infantile onset Abnormality of the skeletal system Short nose Delayed skeletal maturation Absent speech Dyschromatopsia [mendelian.co]
Twinkle mutation in an Italian family with external progressive ophthalmoplegia and parkinsonism: A case report and an update on the state of art. Neurosci. [mdpi.com]
Eyes
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Blurred Vision
vision, cognitive impairment and tremors. [casereports.bmj.com]
Musculoskeletal
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Long Arm
The POLG1 gene is located on the long arm of chromosome 15 (more precise localisation: 15q25). So far, 135 mutations in the POLG1 gene have been identified (The Human Gene Database, as of 09.2010). [labor-lademannbogen.de]
Ears
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Hearing Impairment
impairment Sensorineural hearing impairment Ptosis Cataract SOURCES: UMLS MONDO OMIM ORPHANET More info about PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4; PEOB4 Low match CHARCOT-MARIE-TOOTH DISEASE, X-LINKED [mendelian.co]
Showing of 45 30%-79% of people have these symptoms Abnormal morphology of the cerebellar cortex 0031422 Abnormal thalamic MRI signal intensity 0012696 Atrophy/Degeneration involving the spinal cord 0007344 Bilateral sensorineural hearing impairment 0008619 [rarediseases.info.nih.gov]
Impairment Noonan Syndrome Noonan Syndrome 3 Noonan Syndrome, LEOPARD Syndrome Normal Tension Glaucoma Norrie Disease Nucleoside Phosphorylase Deficiency Obesity, Hyperphagia, and Developmental Delay Obesity, Severe Obesity, Morbid, with Hypogonadism [sequencing.com]
Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. American Journal of Human Genetics 93, 132-140. [mitomap.org]
Neurologic
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Chronic Progressive External Ophthalmoplegia
Disease definition Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome is characterised by adult-onset severe sensory ataxic neuropathy, dysarthria and chronic progressive external ophthalmoplegia. [orpha.net]
progressive external ophthalmoplegia, which results from mitochondrial dysfunction and is due to mtDNA depletion in muscle and peripheral nerve. [link.springer.com]
Chronic progressive external ophthalmoplegia. Current Ocular Therapy. 5th ed. 2000. 208-210. Galetta F, Franzoni F, Mancuso M, Orsucci D, Tocchini L, Papi R, et al. Cardiac involvement in chronic progressive external ophthalmoplegia. [emedicine.medscape.com]
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Headache
Adult Phenotypic Spectrum of Headache, Myopathy and Ischemic Stroke Associated with Mitochondrial POLG Mutation. Austin J Cerebrovasc Dis & Stroke. 2014;1(5): 1021. ISSN: 2381-9103. [austinpublishinggroup.com]
Migraine headache Migraine headaches [ more ] 0002076 Seizures Seizure 0001250 Percent of people who have these symptoms is not available through HPO Adult onset Symptoms begin in adulthood 0003581 Autosomal recessive inheritance 0000007 Cognitive impairment [rarediseases.info.nih.gov]
Spinocerebellar ataxia with epilepsy (SCAE) is a similar disorder with a higher frequency of migraine headaches and seizures ({13:Winterthun et al., 2005}). [diseaseinfosearch.org]
Initial symptoms may include stroke-like episodes, seizures, migraine headaches, and recurrent vomiting. [rarediseasesnetwork.org]
[…] can include myopathy, seizures, and hearing loss, but the common clinical feature appears to be sensory ataxia (review by Milone and Massie, 2010 ).Spinocerebellar ataxia with epilepsy (SCAE) is a similar disorder with a higher frequency of migraine headaches [mendelian.co]
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Positive Romberg Sign
Romberg sign * Depression * Dysphagia * Nystagmus * Reduced position sense * Mild cognitive impairment * Reduced vibration sense * Balance problems * Frequent falls * Muscle weakness * Gastroparesis * Weight loss * Enlarged heart * Stupor * Eye movement [checkorphan.org]
Sensory ataxia is distinguished from cerebellar ataxia by the presence of near-normal coordination when the movement is visually observed by the patient, but marked worsening of coordination when the eyes are shut, indicating a positive Romberg's sign [en.wikipedia.org]
Romberg sign 0002403 Proximal muscle weakness Weakness in muscles of upper arms and upper legs 0003701 Ptosis Drooping upper eyelid 0000508 Ragged-red muscle fibers 0003200 Sensory ataxic neuropathy 0003434 Upgaze palsy 0025331 Vestibular dysfunction [rarediseases.info.nih.gov]
romberg sign 64 65. [slideshare.net]
Romberg sign Abnormality of the cerebral white matter Progressive proximal muscle weakness Ophthalmoparesis Headache Encephalopathy EMG: myopathic abnormalities Limb ataxia Dilated cardiomyopathy Facial palsy Tics Frontal bossing Sensory ataxic neuropathy [mendelian.co]
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Areflexia
Sensory Ataxic form of CIDP • Uncommon • Manifests as prominent numbness in the extremities, ataxia, areflexia and impaired vibration and/or joint position sense • Weakness may be mild or absent 27 28. [slideshare.net]
Other compounds: Carbon disulphide : In rubber vulcanization, distal sensorimotor loss and areflexia affecting the legs. [neuroweb.us]
Weakness in muscles of upper arms and upper legs 0003701 Ptosis Drooping upper eyelid 0000508 Ragged-red muscle fibers 0003200 Sensory ataxic neuropathy 0003434 Upgaze palsy 0025331 Vestibular dysfunction 0001751 5%-29% of people have these symptoms Areflexia [rarediseases.info.nih.gov]
[…] failure Decreased nerve conduction velocity Rhabdomyolysis Motor delay Milia X-linked recessive inheritance Reduced visual acuity Pallor Babinski sign Congenital nystagmus Cerebral atrophy Hypoplasia of the corpus callosum Hyperreflexia Kinetic tremor Areflexia [mendelian.co]
[…] malformation Cardiofaciocutaneous syndrome Carotid-Cavernous Fistula Cat-scratch disease Cataract-glaucoma Celiac disease, epilepsy and cerebral calcification syndrome Central areolar choroidal dystrophy Central precocious puberty Cerebellar ataxia - areflexia [sanfordresearch.org]
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Absent Deep Tendon Reflex
Clinical description Other common features include progressive gait unsteadiness, absent deep tendon reflexes, the presence of Romberg's sign, a decreased sense of vibration and proprioception and detection of red ragged fibres on muscle biopsy. [orpha.net]
The phenotype is largely variable: The common clinical feature appears to be sensory ataxia, and other symptoms include myopathy, seizures, hearing loss, progressive gait unsteadiness, absent deep tendon reflexes, Romberg’s sign, decreased sense of vibration [link.springer.com]
Workup
Hypercoagulable state workup and 28-day prolonged cardiac monitoring were negative. She had sixteen pregnancies and five live births. [austinpublishinggroup.com]
• History of diabetes mellitus and alcohol excess (both common causes of neuropathy) do not preclude the possibility of coexisting pathology • Serum immunoelectrophoresis and immunofixation are, therefore, important investigations in the diagnostic workup [slideshare.net]
Treatment
Key points for each genetic disease are identified to suggest treatment, when available, or the main clinical exams useful in follow-up of patients. [books.google.de]
The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]
The textbookprovides an evidence-based approach to testing, differential diagnosis, and treatment, and should serveas a trusted resource for healthcare professionals confronting the many manifestations of peripheralneuropathy in clinical practice. [books.google.com]
Prognosis
The prognosis for Leigh syndrome is poor. Depending on the defect, individuals typically live a few years. [rarediseasesnetwork.org]
Glucose Tests * Home Urine Ketone Tests * Home Diabetes HbA1c Tests * Home Microalbumin Tests (Kidney) * Home Urine Protein Tests (Kidney) * Home Kidney Tests * Home Eye Tests * Vision & Eye Health: Home Testing: * Home Eye Tests * Home Vision Tests Prognosis [checkorphan.org]
The MTTL1 gene is most often associated with the mitochondrial inheritance pattern, along with other mtRNA and mtDNA genes. [14] Prognosis The prognosis is guarded with a generally progressive disorder. [emedicine.medscape.com]
Favorable prognosis is indicated by preserved action potential preserved R1 or reappearance of R1 after 3 weeks. About 15% of patients will have permanent sequelae. [neuroweb.us]
The prognosis of LS is poor, especially in infancy-onset disease, as most children will die in the first years of life. [clinicaladvisor.com]
Etiology
Etiology The syndrome is associated with mitochondrial DNA mutations in either the POLG1 or TWINKLE genes. Genetic counseling Autosomal recessive and dominant inheritance, as well as sporadic occurrence, have been suggested. [orpha.net]
Lee YM, Kang HC, Lee JS, Kim SH, Kim EY, et al. (2008) Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions. Epilepsia 49: 685-690. [omicsonline.org]
Epidemiology
Summary Epidemiology The prevalence is unknown. [orpha.net]
Epidemiology The prevalence is unknown. [rarediseases.info.nih.gov]
Josef Finsterer 1 * and Sinda Zarrouk-Mahjoub 2 1 Krankenanstalt Rudolfstiftung, Vienna, Austria 2 Genetics Laboratory, Research Unit “Genetics Epidemiology and Molecular” Faculty of Medicine Tunis, Tunisia Corresponding Author : Josef Finsterer Krankenanstalt [omicsonline.org]
The balance of oxidative demands of a given tissue and the proportion of deleted mtDNA it contains will ultimately determine whether the tissue is affected clinically. [12] Epidemiology Frequency Worldwide Worldwide, the prevalence of mitochondrial disease [emedicine.medscape.com]
Pathophysiology
Minagar has significant interest in pathophysiology and neuroimaging features of the inflammatory disease of human central nervous system, in general, and multiple sclerosis, in particular. [books.google.com]
Pathophysiology Mitochondrial DNA (mtDNA) encodes for essential components of the respiratory chain. [emedicine.medscape.com]
[…] article is freely available re-usable Review Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, Department of Pathophysiology [mdpi.com]
Prevention
To help explain this effect we determined that the G451E p55 heterodimer has a weakened ability to bind to p140 which prevents polγ from incorporating the normal amount of DNA building blocks (nucleotides) into newly synthesized DNA. [atlasofscience.org]
Prevention - Sensory ataxic neuropathy- dysarthria- and ophthalmoparesis Not supplied. [checkorphan.org]
Supportive treatment and prevention of further damage from UV light is the mainstay of treatment for dermatological manifestations of XP and DCS. Effective treatment for neurological manifestations of these disorders is not available. [karger.com]
How can mitochondrial disorders be prevented? Since this is a genetically determined disorder, there is no prevention. Prevention of stressors that exacerbate the condition, such as illness, is advocated for all mitochondrial disease. [clinicaladvisor.com]
Treatment for the neuritis and nerve function impairment includes corticosteroids which are used to prevent further damage and facilitate recovery. [neuroweb.us]