Engel / Neuromuscular Disorders 22 (2012) 99–111 PowerPoint Presentation: Exceptions In some CMS the onset is delayed There may be no similarly affected relatives EMG abnormalities may not be present in all muscles, or are present only intermittently [authorstream.com]

They have a varied presentation and progression and very few studies have addressed the natural history. Aim of the present study is to describe the clinical profile and natural history of patients with CMS. [annalsofian.org]

Clinical presentation  Suspected in any person presenting with  Fatigable ocular  Bulbar  Limb weakness during infancy or early childhood  With a positive family history(autosomal recessive except slow channel) 28.  Response to cholinesterase inhibitors [slideshare.net]

Neonates present with feeding problems, choking, feeble cry, and muscle weakness. Patients presenting in later childhood are seen with abnormal exercise-induced fatigue and difficulty running. [preventiongenetics.com]

Familiarity was present in 4 patients (mother in patients 1, 3, and 6; first cousin in patient 2). [pediatricneurosciences.com]

• Epilepsy

  […] pediatric neurology evolved as an identified specialty as the volume and complexity of data became too much for the general pediatician or the adult neurologist to master, the discipline has now continued to evolve into so many subspecialties, such as epilepsy [books.google.com]

  Clinical Practice. 6 th edition PowerPoint Presentation: Vs Congenital Muscular dystrophies diffuse weakness and hypotonia significant elevations in serum CK subcortical white matter abnormalities may be seen on brain MRI, cognition is usually normal Epilepsy [authorstream.com]

• Wheelchair Bound

  Treatment with pyridostigmine and 3,4-diaminopyridine had a limited beneficial effect in the first patient, and the second patient became wheelchair-bound during therapy. [pediatricfocus.wordpress.com]

• Respiratory Insufficiency

  Congenital myasthenic syndromes caused by ChAT mutations  Manifest at birth or in the neonatal period with bulbar disorders and respiratory insufficiency with apnoea or even sudden death.  Triggered by fever, fatigue and overexertion.  Apart from these [slideshare.net]

  One of them has mild symptoms including difficulties in gait and feeding with mild respiratory insufficiency while the other died within the first month of life because of severe respiratory failure. [degruyter.com]

  insufficiency precipitated by intercurrent infections A.G. [authorstream.com]

  Life threatening respiratory insufficiency may occur in affected neonates or older children. [blueprintgenetics.com]

  Other features, such as congenital arthrogryposis multiplex and respiratory insufficiency, may also occur (PMID: 25159927). [invitae.com]

• Respiratory Distress

  distress and bulbar paralysis.  Electrophysiology of the intercostal Muscle-the impossibility of evoking an action potential after nerve stimulation.  Two mutations of SCN4A were identified. 21.  Previously named ‘myasthenic myopathy’  Autosomal [slideshare.net]

  Diagnostic criteria ( 1 ) include an onset at birth to early childhood, with fluctuating ptosis, poor cry and suck, feeding difficulties and possible respiratory distress. [academic.oup.com]

  At birth, they may present with hypotonia, respiratory distress or joint contractures. [annalsofian.org]

• Respiratory Disorders

  Congenital myasthenic syndromes caused by ChAT mutations  Manifest at birth or in the neonatal period with bulbar disorders and respiratory insufficiency with apnoea or even sudden death.  Triggered by fever, fatigue and overexertion.  Apart from these [slideshare.net]

• Myopathy

  Myopathy, centronuclear 160150 DNM2 dynamin 2 Myopathy, distal, Tateyama type 614321 CAV3 caveolin 3 Myopathy, distal, with anterior tibial onset 606768 DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) Myopathy, myofibrillar, 1 [ac-gen.com]

   Presents with progressive myopathy, associated with myasthenic syndrome (involving facial, limb and oculomotor muscles), and epidermolysis bullosa 20.  Presents since birth with very short bouts (3– 30 min) of respiratory distress and bulbar paralysis [slideshare.net]

  Lorenzoni et al. / Pediatric Neurology 46 (2012) 141-148 PowerPoint Presentation: Agrin deficiency- Ephedrine, 3,4-DAP With tubular aggregates- Pyridostigmine Other defects( Plectin, With centronuclear myopathy )- 3,4-DAP, Pyridostigmine P.J. [authorstream.com]

  Multiple pterygium syndrome, Escobar syndrome AR 17 34 COLQ Myasthenic syndrome, congenital AR 23 67 DOK7 Myasthenic syndrome, congenital AR 28 75 DPAGT1 Congenital disorder of glycosylation, Myasthenic syndrome, congenital AR 16 32 FLAD1 Lipid storage myopathy [blueprintgenetics.com]

  Chicago) two years before this SC-CMS was reported, and now a fundamental aspect of the proposed research is to define the mechanism by which this novel lipid-exposed mutant leads to endplate myopathy in humans. (2) In vivo, lipid-protein interactions [nachrs.org]

• Encephalopathy

  De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy. Genet Med. 2021;23:653–60. [PubMed: 33299146] Lamond A, Buckley D, O'Dea J, Turner L. [ncbi.nlm.nih.gov]

For developmental delay, she has been evaluated by the Pediatric Neurology and Medical Genetics units and her workup is as follows: Tandem Mass Spectrometry (TMS), urine Gas Chromatography–Mass Spectrometry (GC-MS), Microarray Comparative Genomic Hybridization [degruyter.com]

This will allow close monitoring and early intervention in the case of respiratory failure and will also expedite the diagnostic workup and initiation of therapy. 4. [neupsykey.com]

Treatments for CMS Autosomal recessive inheritance CMS Type Affected Genes Treatment AChR Deficiency - postsynaptic CHRNA1, CHRNB1, CHRND, CHRNE Pyridostigmine, 3,4-DAP, Salbutamol* / Ephedrine* RAPSYN CMS - postsynaptic RAPSN Pyridostigmine, 3,4-DAP [myaware.org]

The patient showed modest benefits from standard treatment with fluoxetine, but there was dramatic improvement when salbutamol was combined with fluoxetine. [pediatricfocus.wordpress.com]

". [6] Treatment depends on the form (category) of the disease. [en.wikipedia.org]

This network is dedicated to the acceleration of clinical trials in search of effective treatments for SMA. [books.google.com]

Experimental: amifampridine phosphate -placebo Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. [clinicaltrials.gov]

Congenital myasthenic syndromes: Natural history and long-term prognosis. Ann Indian Acad Neurol 2013;16:338-41 How to cite this URL: Jagtap SA, Abraham K, Sarada C, Nair M D. Congenital myasthenic syndromes: Natural history and long-term prognosis. [annalsofian.org]

Prognosis in CMS is variable and largely depends on the pathophysiological and genetic defect. Subtypes showing progression and life-threatening crises with apneas are generally less favorable than others. [link.springer.com]

Disord., 2015, 25(3), 253-6 Crossref PubMed Google Scholar [4] Jagtap S.A., Abraham K., Sarada C., Nair M.D., Congenital myasthenic syndromes: Natural history and long-term prognosis, Ann. Indian Acad. [degruyter.com]

Prognosis. Natural course: Appropriate management of the patient with autoimmune MG requires understanding of the natural course of the disease. The long-term natural course of MG is highly variable but generalizations are as follows. [neupsykey.com]

CMS diagnosis typically depends on a combination of factors, including clinical presentation, family history, genetic etiology, negative anti-ACh and anti-MuSK serum studies, and decremental electromyographic findings (PMID: 23622369). [invitae.com]

Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes. Eur J Paediatr Neurol. 2011 May;15(3):189-96. doi: 10.1016/j.ejpn.2011.03.006. Epub 2011 Apr 17. Review. [ghr.nlm.nih.gov]

Prognosis in CMS is variable and largely depends on the pathophysiological and genetic defect. Subtypes showing progression and life-threatening crises with apneas are generally less favorable than others. [link.springer.com]

The disease manifestations differ according to the time of its onset and the underlying neuromuscular pathophysiology [ 3 ]. [degruyter.com]

Prevention A specific diagnosis of CMS is critical as some medications that benefit one type of CMS can be detrimental in another type (Engel, A., 2007. PubMed ID:17395135). [preventiongenetics.com]

 Immediate treatment of respiratory distress  Prevention of infections and of malnutrition as a result of swallowing disorders  Orthopaedic surveillance of spinal complications and retractions 33.  Cholinesterase inhibitors are efficient in all [slideshare.net]

Prophylactic anti-cholinesterase therapy has been recommended to prevent sudden respiratory insufficiency or apneic attacks provoked by fever or infections in those with mutations in ChAT or RAPSN. [ 9 ] Parents of an affected infant must be advised to [degruyter.com]

In vitro functional expression studies showed that the I58K substitution prevented expression of the delta subunit and was a null mutation. [genome.jp]

The Center for Disease Control and Prevention (CDC) recommends administration of one vial of antitoxin for adult patients with botulism as soon as diagnosis is made, without waiting for laboratory confirmation; before administration of antitoxin, consider [neupsykey.com]