Materiały źródłowe

• #1 Congenital myasthenic syndromes – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/congenital-myasthenic-syndrome/symptoms-causes/syc-20354754

  Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, which worsens with physical activity. […] There is no cure for congenital myasthenic syndromes. Medications are generally an effective treatment for muscle weakness symptoms. Which medication works depends on which gene is identified as the cause of the congenital myasthenic syndrome. […] Rarely, some children may have a mild form that doesn’t need treatment.

• #2 Congenital myasthenic syndromes // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/congenital-myasthenic-syndromes

  There is no cure for congenital myasthenic syndromes. Medications are generally an effective treatment for muscle weakness symptoms. Which medication works depends on which gene is identified as the cause of the congenital myasthenic syndrome. Rarely, some children may have a mild form that doesn’t need treatment. […] Medications aren’t a cure, but they can improve muscle contraction and muscle strength in people with congenital myasthenic syndromes. Which medications are effective depends on the type of affected gene. Medications that are effective for one type of syndrome may be ineffective for another type, so genetic testing is recommended before starting medications. […] Medication treatment options may include: Acetazolamide, 3,4-diaminopyridine (3,4-DAP), marketed as amifampridine (Firdapse, Ruzurgi), Albuterol, Ephedrine, Fluoxetine (Prozac), Neostigmine (Bloxiverz), Pyridostigmine (Mestinon, Regonol).

• #3 Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6436731/

  We perform a systematic review of the evidence for pharmacological treatment of each CMS type, gathering evidence from 207 studies of over 1000 patients and stratifying by genetic defect, as treatment varies depending on the underlying cause. […] Most CMS subtypes are nevertheless amenable to some form of pharmacotherapy, but pharmacological treatment varies by subtype, with the drugs appropriate for one type potentially making another worse. […] Treatment strategies are illustrated in Figure 1 and Table 1, and are broadly dependent on whether it is beneficial to increase the amount of acetylcholine available in the synaptic cleft (for which commonly administered therapies include AChE inhibitors such as pyridostigmine, which inhibits acetylcholine breakdown, and the potassium-channel blocker 3,4-diaminopyridine, which increases the quantal release of acetylcholine) or to shorten the excessive duration of synaptic current in slow-channel syndromes by reducing the channel-open time (for which the open-channel blockers fluoxetine and quinidine may be used).

• #4 Medical Management – Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/congenital-myasthenic-syndromes/medical-management

  The cholinesterase inhibitors used to treat myasthenia gravis (MG) are helpful in some types of congenital myasthenic syndromes (CMS) but may be harmful in others. […] Its important to realize that because CMS isnt an autoimmune disease, it doesnt respond to immunosuppressant drugs or other treatments aimed at the immune system. […] Cholinesterase inhibitors boost levels of acetylcholine (ACh) a chemical necessary for proper muscle function not only at the neuromuscular junction but also in the autonomic nervous system (which controls involuntary bodily functions). […] The types of CMS that respond to cholinesterase inhibitors include: Presynaptic CMS, Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) In addition to cholinesterase inhibitors, this type is also treated with amifampridine containing drugs that enhance ACh release. […] Types of CMS that do not respond to cholinesterase inhibitors include: Postsynaptic CMS (slow-channel CMS) This type is treated with quinidine or fluoxetine, both of which plug the ACh receptor. […] Synaptic CMS There currently are no drug treatments for this type of CMS.

• #5 Congenital Myasthenic Syndromes: a Clinical and Treatment Approach – PubMed

  https://pubmed.ncbi.nlm.nih.gov/30032336/

  Unlike in autoimmune myasthenia gravis, there is no role for immunotherapy in congenital myasthenic syndromes. If available, a genetic diagnosis should drive the choice for a first-line treatment agent between cholinergic agents, -adrenergic agents, and open-channel blockers. Evaluation and supportive care at centers with experience in these rare syndromes likely are paramount in achieving optimal outcomes. Furthermore, gene discovery for congenital myasthenic syndromes has provided novel insights on the role of protein glycosylation, endplate maintenance and repair, and synaptic vesicle exocytosis in neuromuscular transmission. These insights may lead to new therapeutic strategies in both congenital and autoimmune myasthenic diseases in the future.

• #6 Congenital Myasthenic Syndrome Treatment

  https://practicalneurology.com/articles/2019-aug-july/congenital-myasthenic-syndrome-treatment

  Therapy for CMS is focused on alleviating symptoms and typically includes pharmacologic treatment, although nonpharmacologic treatment has been reported. […] Acetylcholinesterase inhibitors (AChEIs) (eg, pyridostigmine) are the most commonly used drugs for CMS. […] Although pyridostigmine monotherapy is effective for some individuals, others benefit from combination therapy, often in the form of 3,4-diaminopyridine (3,4-DAP), to achieve an effective and/or sustained response. […] Alternative drugs, either given alone or in combination with an AChEI and/or 3,4-DAP include albuterol, ephedrine, fluoxetine, and quinidine. […] Combination therapies have also been used as a first-line option, particularly in cases where CMS subtypes are known to respond negatively or not at all to AChEI monotherapy (eg, DOK7 mutations) or as second- and third-line options for people with CMS refractory to AChEI treatment.

• #7 Congenital Myasthenic Syndrome Treatment

  https://practicalneurology.com/articles/2019-aug-july/congenital-myasthenic-syndrome-treatment

  Of the AChEIs, which are the most commonly used first-line treatment for CMS, pyridostigmine is most frequently used, followed by neostigmine and ambenonium. […] The AChEIs are effective for many forms of CMS including CHRNE and RAPSN and glycosylation defects. […] For some subtypes, however, AChEIs are ineffective and may worsen symptoms, including mutations in components that act to cluster AChRs at the NMJ (eg, COLQ, COL13A1, LAMB2, DOK7, LRP4, and MUSK). […] Amifampridine, or 3,4-DAP, is the most frequently used alternative to AChEIs and is also often given in combination with AChEIs. […] Albuterol has been effective for treating synaptic CMS (eg, COL13A1 or COLQ mutations) and postsynaptic CMS (eg, LRP4, MUSK, and DOK7). […] Ephedrine may enhance NMT by stimulating 2-adrenergic receptors and stabilizing NMJ structure.

• #8 Congenital Myasthenic Syndromes: a Clinical and Treatment Approach – PubMed

  https://pubmed.ncbi.nlm.nih.gov/30032336/

  Congenital myasthenia syndromes are clinically and genetically heterogeneous but treatable conditions. Careful selection of drug therapy is paramount as the same drug can be effective, ineffective, and even harmful in different congenital myasthenia syndromes. The purpose of this article is to review current treatment options for these conditions. […] Cholinergic agents, -adrenergic agonists, and open-channel blockers remain the principal treatment modalities, and their optimal use depends on an accurate genetic diagnosis and the timely clinical recognition of the disease. In particular, pyridostigmine, usually a first-line agent, should be avoided in DOK7, acetylcholinesterase deficiency, and slow-channel congenital myasthenic syndromes. Beta-adrenergic agonists have been recognized as a first-line agent for a number of congenital myasthenic syndromes, particularly DOK7 and acetylcholinesterase deficiency, whereas long-lived open-channel blockers of the acetylcholine receptor (AChR) ion channel are indicated for the slow-channel congenital myasthenic syndrome. Beta-adrenergic agonists additionally have an important adjunct treatment for congenital myasthenia syndrome due to glycosylation defects, fast channel syndrome, AChR deficiency, and choline acetyltransferase deficiency (ChaT) and therefore may be particularly important in the treatment of syndromes due to defects in motor endplate development and repair.

• #9

  https://journals.lww.com/co-neurology/fulltext/2019/10000/the_congenital_myasthenic_syndromes__expanding.8.aspx

  Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins whose function is essential for the integrity of neuromuscular transmission. This review updates the reader on the expanding phenotypic spectrum and suggested improved treatment strategies. […] Recent studies of the CMS illustrate the increasing complexity of the genetics and pathophysiological mechanisms involved. With therapy tailored for the underlying disease mechanism treatment, although incomplete, is usually life-transforming. However, treatment for newly identified conditions in which myasthenia is only one component within complex multisystem disorder will prove challenging. […] The current repertoire of drugs for use in CMS includes as follows: Drugs that increase ACh release, such as potassium blockers (3,4-diaminopyridine); drugs that maintain high ACh concentrations within the synaptic cleft, such as AChE inhibitors (mainly pyridostigmine); 2-adrenergic receptor agonists (ephedrine, salbutamol); and ACh receptor (AChR) open-channel blockers (fluoxetine, quinidine).

• #10

  https://journals.lww.com/co-neurology/fulltext/2019/10000/the_congenital_myasthenic_syndromes__expanding.8.aspx

  For many years reversible, competitive AChE inhibitors, such as pyridostigmine, were the mainstay of treatment for myasthenia. By blocking the action of AChE, the presence of ACh within the synapse is prolonged thus giving a greater probability of reaching the depolarization threshold for generation of the muscle action potential. […] Now, with greater understanding of the mutations and molecular mechanisms underlying CMS treatments can be tailored for the specific syndrome and depending on diseases severity and patient response this can include utilizing different combinations of the drugs. […] Adrenergic agonists, in particular ephedrine, have been used for the treatment of myasthenia, since the 1930s, but were largely replaced once AChE inhibitors were found to be effective in symptomatically treating myasthenia gravis.

• #11 DOK7 congenital myasthenic syndrome: case series and review of literature | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03713-0

  Congenital myasthenic syndromes (CMS) are among the most challenging differential diagnoses in the neuromuscular domain, consisting of diverse genotypes and phenotypes. DOK7 CMS requires different treatment than other CMS types. […] We recommend prescribing salbutamol as the first-choice treatment option for DOK7 patients. […] DOK7 CMS requires different treatment than other CMS types, and patients generally respond very well to oral salbutamol. […] Salbutamol was the most effective. […] We strongly recommend that neurologists consider CMS in patients with these symptoms and a similar familial history. […] Considering that DOK7 patients deteriorate on pyridostigmine, the authors initiated pyridostigmine in these patients because they prescribed it before the genetic diagnosis. They discontinued pyridostigmine after observing the deteriorating effect of this medication on patients or after seeing the genetic results.

• #12 Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes

  https://ctv.veeva.com/study/efficacy-of-albuterol-in-the-treatment-of-congenital-myasthenic-syndromes

  The study tests the notion that patients suffering from certain types of congenital myasthenic syndromes are benefitted by the use of Albuterol at doses used in clinical practice. […] The aim of the proposal is to evaluate the effects of albuterol, an adrenergic agonist, in the treatment of congenital myasthenic syndromes (CMS). […] After ephedrine became unavailable, I treated the same type of patients with albuterol in doses ranging from 4 mg daily to twice daily for adults; the dose for children 6 to 12 years is 2 mg two or three times daily; the dose for children 2 to 6 years is 0.1 mg/kg/day (maximum 2 mg) three times daily. […] Albuterol Experimental group Description: 4 mg twice daily by mouth for adults. The dose for children 6 to 12 years is 2 mg two or three times daily; the dose for children 2 to 6 years is 0.1 mg/kg/day (maximum 2 mg) three times daily.

• #13 Wide heterogeneity of congenital myasthenic syndromes: analysis of clinical experience in a tertiary center

  https://www.e-kjgm.org/journal/view.html?doi=10.5734/JGM.2020.17.2.73

  The response to treatment depends on the subtype of CMS. Traditionally, pyridostigmine, a competitive acetylcholinesterase inhibitor, was the mainstay of treatment for the neuromuscular junction disorders. Oral pyridostigmine can be given at an initial dose of 0.5 to 1 mg/kg every 4 to 6 hours and the maximum recommended total daily dose is 7 mg/kg. Consistent with previous reports, our patients with defects of acetylcholine receptor, presynaptic choline transporter, and protein glycosylation had much benefited from pyridostigmine. But some subtypes such as endplate acetylcholinesterase deficiency due to COLQ mutations and DOK7-related CMS are known to refractory or deteriorate with pyridostigmine. […] Whereas salbutamol were very effective in patients with DOK7 and COLQ deficiency and partially beneficial in other subtypes of CMS. Oral salbutamol can be given at an initial dose of 4 mg/day and titrated up to 12 mg/day. A 3,4-Diaminopyridine (amifampridine; Ruzurgi, available at Korean Orphan Essential Drug Center) is a potassium channel blocker working on the presynaptic nerve terminal. The pediatric starting dose is 0.25-0.5 mg/kg/day and titrated up to 1 mg/kg/day total dose if necessary. It was a useful add-on therapy for the patients with mutations of DOK7, AGRN, COLQ, and GFPT1 in our experience.

• #14 DOK7 congenital myasthenic syndrome: case series and review of literature | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03713-0

  Salbutamol stabilizes NMJ structure by decreasing the detrimental effects of long-term acetylcholinesterase inhibitors on the post-synaptic NMJ and reducing the dispersion of the ACh receptor. […] Oral salbutamol is also effective in AChR deficiency. It is especially effective in severe cases where patients are on long-term pyridostigmine therapy, destabilizing the post-synaptic muscle membrane. […] Salbutamol improved the condition of all seven patients in our study.

• #15

  https://journals.lww.com/co-neurology/fulltext/2024/10000/congenital_myasthenic_syndromes__increasingly.9.aspx

  Currently there are no licensed drugs specifically for CMS treatment and all the drugs used are off-label, the doses and formulations used in CMS can be different to the licensed uses. Given that CMS is a heterogeneous disorder with many different underlying molecular mechanisms, the treatment response depends upon the subtype of CMS and treatment needs to be tailored for disease severity and patient response and can involve utilizing different combinations of the drugs. […] The common drugs used are acetylcholinesterase inhibitors (Pyridostigmine), 3,4 diaminopyridine (3,4-DAP), Salbutamol and Ephedrine. Fluoxetine and Quinidine are used in slow channel CMS. […] Acetylcholinesterase inhibitors slow the breakdown of acetylcholine in the synaptic cleft and hence prolong its activity. Pyridostigmine (Mestinon) is most commonly prescribed and is the first-line treatment in presynaptic CMS, AChR deficiency CMS, fast channel CMS and CMS due to glycosylation defects. […] 3,4-DAP is a potassium channel blocker and works on the presynaptic nerve terminal by prolonging the motor nerve action potential, and hence increasing the release of acetylcholine into the synaptic cleft. […] Beta 2-adrenergic receptor agonists include Ephedrine, and Salbutamol (Albuterol in the USA) are treatment of choice in DOK 7 and COLQ CMS. They are proposed to stabilize the synaptic structure and hence the effects can take several months to have an optimal effect. […] Several studies have published promising data from preclinical trials on novel therapeutics for CMS. These include using adeno-associated viruses (AAV) to deliver gene replacement therapies for treating deficiencies in DOK7, COLQ and CHAT, as well as a MUSK agonist antibody therapy that rescued a DOK7-CMS mouse model. […] New therapeutic strategies aimed at improving neuromuscular transmission in myasthenia gravis by either inhibiting chloride channels to lower the safety factor, or by positive allosteric modulation of nAChR activity are intriguing as these strategies may also be applicable for treating a variety of subtypes of CMS.

• #16 Congenital Myasthenic Syndrome Treatment

  https://practicalneurology.com/articles/2019-aug-july/congenital-myasthenic-syndrome-treatment

  Fluoxetine is often used as first-line treatment for SCCMS in adults or when AChEI are ineffective. […] There are a few reports of other treatments, including acetazolamide, amiloride, spironolactone, theophylline, azathioprine, prednisone, and quinidine. […] Noninvasive, nonpharmacologic treatments include physical therapy, speech therapy, and occupational therapy. […] For those with respiratory insufficiency, nasal intermittent positive pressure ventilation (NIPPV) may be used either constantly or at night only. […] Invasive, nonpharmacologic treatments for CMS are also available for various symptoms. […] Diagnosis and management of CMS have evolved from clinical observation, to EMG assessments investigating subcellular mechanisms of impaired NMT, to genetic assessment pinpointing specific gene mutations.

• #17 Congenital myasthenic syndromes | MedLink Neurology

  https://www.medlink.com/articles/congenital-myasthenic-syndromes

  Congenital myasthenic syndromes are inherited disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. […] Most congenital myasthenic syndromes are treatable, but therapy has to be tailored for the underlying molecular defect because therapies beneficial in some congenital myasthenic syndromes can be harmful in another type. […] Cholinergic agonists benefit the congenital myasthenic syndromes caused by low-expressor and fast-channel mutations in AChR subunits, rapsyn, choline acetyltransferase, and glutamine-fructose-6-phosphate transaminase 1 (GFPT1) and are of variable benefit in congenital myasthenic syndromes caused by mutations in DPAGT1. […] The slow-channel syndrome responds to the long-lived open-channel blockers of AChR, like fluoxetine, quinine, or quinidine.

• #18 Congenital myasthenic syndromes | MedLink Neurology

  https://www.medlink.com/articles/congenital-myasthenic-syndromes

  The congenital myasthenic syndromes caused by defects in Dok7, LRP4, and ColQ respond to ephedrine or albuterol. Albuterol is also beneficial as an adjuvant to cholinergic agonists in congenital myasthenic syndromes caused by defects in rapsyn and by low-expressor mutations in AChR subunits. […] Because medications that benefit one type of syndrome can worsen another type, a correct genetic diagnosis is essential before treatment is initiated. […] In general terms, the congenital myasthenic syndromes either decrease or increase the synaptic response to ACh. When a congenital myasthenic syndrome reduces the synaptic response, cholinesterase inhibitors, which increase the number of AChRs activated by each quantum, and 3,4-DAP, which increases the number of quanta released by nerve impulse, are used.

• #19 Congenital myasthenic syndromes | MedLink Neurology

  https://www.medlink.com/articles/congenital-myasthenic-syndromes

  However, in some congenital myasthenic syndromes caused by defects in MuSK, Dok7, AGRN, and LRP4, cholinergic agonists can be harmful, but these disorders often respond to ephedrine or albuterol. […] When the synaptic response is increased, as in the slow-channel syndromes, long-lived open-channel blockers of the AChR channel, quinidine and fluoxetine, are employed. […] That some agents are beneficial in one type of congenital myasthenic syndrome but harmful in others underlines the need for a specific diagnosis. […] Most patients respond favorably but incompletely to cholinesterase inhibitors. The additional use of 3,4-DAP results in further significant improvement in about one third of the cases. […] Albuterol may also benefit patients not responding well to cholinergic agonists.

• #20 Congenital myasthenic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Congenital_myasthenic_syndrome

  Postsynaptic fast-channel CMS, in which ACh receptors do not stay open long enough, is treated with cholinesterase inhibitors and 3,4-diaminopyridine. In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program. Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which blocks the ACh receptor. […] Ephedrine, a (2)-adrenergic receptor agonist with alpha activity, has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be substantial. The effect of ephedrine is delayed and the improvement occurs over a period of months.

• #21 Myasthenic Syndromes | PM&R KnowledgeNow

  https://now.aapmr.org/myasthenic-syndromes/

  For CMS, treatment depends on the subtype. Pyridostigmine and other cholinergic agonists often work well for the fast-channel post-synaptic conditions or ACh deficiency. They will typically worsen the slow channel post-synaptic conditions, defective AChR clustering (DOK7 mutation), and synaptic (COLQ mutation) cases. […] For JMG, first line treatment includes anti-AChEs, such as pyridostigmine, +/- corticosteroids. Immunosuppressive agents, such as azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil, rituximab may also be considered. IVIG may be implemented in higher acuity cases or crisis. […] Thymectomy is an option if pharmacological treatment fails or in AChR-Ab positive generalized JMG patients; however, there is a lack of large prospective cohort studies for data to standardize this treatment for JMG.

• #22 Congenital myasthenic syndromes – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/congenital-myasthenic-syndrome/diagnosis-treatment/drc-20557730

  Rarely, some children with mild congenital myasthenic syndromes may not need treatment. […] Medications aren’t a cure, but they can improve muscle contraction and muscle strength in people with congenital myasthenic syndromes. Which medications are effective depends on the type of affected gene. Medications that are effective for one type of syndrome may be ineffective for another type, so genetic testing is recommended before starting medications. […] Medication treatment options may include: Acetazolamide, 3,4-diaminopyridine (3,4-DAP), marketed as amifampridine (Firdapse, Ruzurgi), Albuterol, Ephedrine, Fluoxetine (Prozac), Neostigmine (Bloxiverz), Pyridostigmine (Mestinon, Regonol). […] Supportive treatments depend on the type and severity of the congenital myasthenic syndrome. Options may include: Therapies. Physical, speech and occupation therapies may help maintain function. Therapy also can offer supportive devices, such as wheelchairs, walkers, and hand and arm supports.

• #23 Congenital myasthenic syndromes – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/congenital-myasthenic-syndrome/diagnosis-treatment/drc-20557730

  Breathing support. Some congenital myasthenic syndromes may result in pauses in breathing, called apnea. Using an apnea monitor may be recommended. Noninvasive positive-pressure ventilation, such as a continuous positive airway pressure (CPAP) mask and machine, may be used to support breathing and oxygenation. In some cases, intubation and use of mechanical ventilation may be needed. […] Feeding support. Problems with chewing and swallowing may require additional nutrition. Enteral nutrition, also known as tube feeding, is a way of delivering nutrition directly into the stomach or small intestine. Your doctor may recommend a procedure to place a tube through the skin on the abdomen and into the stomach (gastrostomy) or into the small intestine (jejunostomy). […] Surgery. For severe orthopedic deformities, such as in the spine or feet, surgical correction may be needed. […] Regular follow-up appointments with a team of medical professionals provides ongoing care and may help prevent certain complications. Your health care team can link you with appropriate support for home, school or work.

• #24 Congenital myasthenic syndromes (CMS) – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/conditions/a-z/congenital-myasthenic-syndrome-cms/

  CMS can be classified based on where the problem happens along the signal route: […] There are medications that can help improve and maintain muscle function in people with CMS. However, some medications that benefit some types of CMS can worsen other types, so its important to have a genetic diagnosis before starting treatment. The most commonly used medication is pyridostigmine, followed by 3,4 diaminopyridine (3,4-DAP), salbutamol, ephedrine, and fluoxetine. […] The level of breathing weakness can vary from mild to life-threatening, so appropriate management is crucial. Respiratory function and lung capacity should be monitored at regular checkups where possible. […] Its important to stay active and do regular gentle exercise to maintain muscle strength. […] A speech and language therapist can carry out an assessment and provide support if facial and throat weakness is affecting speech or swallowing. […] Some medications can interfere with neuromuscular transmission or muscle function and worsen CMS symptoms. […] Before having any surgery or treatment, its essential to tell the anaesthetist and surgical team of a CMS diagnosis.

• #25 Congenital Myasthenic Syndromes – EyeWiki

  https://eyewiki.org/Congenital_Myasthenic_Syndromes

  Different subtypes of CMS are likely to have different response to medications, due to the underlying pathology of the disorder. The most common medications taken for CMS are acetylcholinesterase inhibitors, and 3,4-diaminopyridine (3,4-DAP), a potassium channel blocker, is the most common alternative or added pharmacologic treatment. Most patients have a partial beneficial response to one or both medications. However, acetylcholinesterase inhibitors tend to be ineffective in patients with CMS mutations in COLQ, LAMB2, DOK7, MUSK, or LRP4. 3,4-DAP can be ineffective with CHRNE or MUSK mutations. Other medications that may be used to manage symptoms include salbutamol, albuterol, ephedrine, and fluoxetine, depending on the specific CMS subtype. […] Side effects of medications should be monitored carefully. Some medications may exacerbate weakness and precipitate respiratory failure. […] Patients with CMS are likely to require regular lifelong follow up to monitor for extent and progression of symptoms as well as efficacy of therapy. Muscle strength and respiratory function should be routinely assessed.

• #26 Congenital Myasthenic Syndromes (CMS) – Rare Awareness Rare Education

  https://rareportal.org.au/rare-disease/congenital-myasthenic-syndromes-cms/

  It is best to speak with your medical team to learn more about possible treatments for a specific type of congenital myasthenic syndromes (CMS) and its associated symptoms. Treatment will depend on the type of CMS as well as an individuals specific symptoms and complications; each individual may respond to a particular treatment differently. […] Healthcare professionals involved in the treatment of congenital myasthenic syndromes (CMS) may include general practitioners (GP), genetic counsellors or clinical geneticists, neurologists, ophthalmologists, occupational therapists, speech pathologists, physiotherapists, and exercise physiologists. The need for different healthcare professionals may change over a persons lifetime and extend beyond those listed here.

• #27 Improving gene therapy for congenital myasthenic syndrome – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/research/current-projects/improving-gene-therapy-for-congenital-myasthenic-syndrome/

  Dr Yin Dong and his team at the University of Oxford will use a mouse model of congenital myasthenic syndrome to test the efficacy of gene therapy in combination with a standard treatment for this condition. […] Standardised treatments are available, but their efficiency is quite poor and rarely lead to an improved lifestyle for people living with CMS. […] Gene therapy that increases the amounts of DOK7 in mouse models has previously been shown to improve the physical activity of mice in models for the conditions DOK7-CMS, amyotrophic lateral sclerosis, spinal muscular atrophy, and age-related motor impairment. […] The main aims of this research include: Determine if the combination of the DOK7 gene therapy and the standard treatment is more effective than the standard treatment alone by using receptor-deficiency CMS mouse models.

• #28 Advances in the diagnosis and treatment of congenital myasthenic syndrome

  http://www.zgddek.com/EN/abstract/abstract25019.shtml

  Congenital myasthenic syndrome (CMS) is a group of clinical and genetic heterogeneous diseases caused by impaired neuromuscular transmission due to genetic defects. […] Pharmacotherapy and symptomatic/supportive treatment are the main methods for the treatment of CMS, and antisense oligonucleotide technology has been proven to be beneficial for CHRNA 1-related CMS in animals. […] an understanding of the latest knowledge and research advances in its clinical features, genetic research, and treatment helps to give early diagnosis and treatment as well as gain a deeper understanding of the pathogenesis of CMS, so as to make new breakthroughs in the treatment of CMS. […] Antisense oligonucleotide-mediated exon skipping of CHRNA1 pre-mRNA as potential therapy for congenital myasthenic syndromes.

• #29 Research – Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/congenital-myasthenic-syndromes/research

  In the past, people with congenital myasthenic syndromes (CMS) were often told they had myasthenia gravis (MG) and were subjected to years of pointless immunosuppressive therapy. […] By identifying the genetic defects that cause CMS, MDA-funded scientists have improved the diagnosis of CMS and discovered drugs that are effective against it. […] MDA-supported scientists are continuing to probe the genetic and molecular underpinnings of the various congenital myasthenic syndromes so that specific treatments for these can be developed or refined. […] Current projects include the development of a new mouse model of a congenital myasthenic syndrome; genetic analysis of a worm with a slow-channel myasthenic syndrome; studies of how the nerve-muscle junction forms; and overall methods to improve the diagnosis, treatment and prevention of congenital myasthenic syndromes.

• #30 Congenital myasthenic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Congenital_myasthenic_syndrome

  Congenital myasthenic syndrome (CMS) is „often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not.” Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the „initiation of specific treatment.” […] Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments. A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.

• #31 Congenital Myasthenic Syndromes – EyeWiki

  https://eyewiki.org/Congenital_Myasthenic_Syndromes

  Congenital myasthenic syndromes (CMS) result from a variety of mutations affecting the neuromuscular junction and are characterized by fatigability and weakness of different muscle groups, commonly including the ocular muscles. CMS is diagnosed via a combination of clinical findings and genetic testing. Pharmacologic treatment is primarily aimed at symptomatic management. […] There are no standardized treatment guidelines for CMS. The rarity of the disease makes it challenging to conduct adequately powered double-blind, placebo-controlled clinical trials. Current treatments aim to improve symptoms, but dosing, duration, treatment combinations, and side effects tend to be poorly specified. […] Genetic subtyping should be conducted to inform medical treatment. Non-medical treatment options, such as physical therapy, occupational therapy, speech therapy, orthotics, or non-invasive positive pressure ventilation should also be considered based on a patients particular symptoms to optimise their function.

• #32 Congenital myasthenic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Congenital_myasthenic_syndrome

  Salbutamol, a selective (2)-adrenergic receptor agonist, has been found, in adults, to have fewer side effects than Ephedrine and to be more easily obtained in some countries. It has been trialed in children with positive results. […] As of 2022, the standard of care for DOK7 CMS is either ephedrine or salbutamol.

• #33

  https://journals.lww.com/co-neurology/fulltext/2019/10000/the_congenital_myasthenic_syndromes__expanding.8.aspx

  Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins whose function is essential for the integrity of neuromuscular transmission. This review updates the reader on the expanding phenotypic spectrum and suggested improved treatment strategies. […] Recent studies of the CMS illustrate the increasing complexity of the genetics and pathophysiological mechanisms involved. With therapy tailored for the underlying disease mechanism treatment, although incomplete, is usually life-transforming. However, treatment for newly identified conditions in which myasthenia is only one component within complex multisystem disorder will prove challenging. […] The current repertoire of drugs for use in CMS includes as follows: Drugs that increase ACh release, such as potassium blockers (3,4-diaminopyridine); drugs that maintain high ACh concentrations within the synaptic cleft, such as AChE inhibitors (mainly pyridostigmine); 2-adrenergic receptor agonists (ephedrine, salbutamol); and ACh receptor (AChR) open-channel blockers (fluoxetine, quinidine).

• #34 Improving gene therapy for congenital myasthenic syndrome – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/research/current-projects/improving-gene-therapy-for-congenital-myasthenic-syndrome/

  This research could allow for discovery and generation of more efficient therapies for receptor-deficiency CMS, allowing people with the condition to potentially have an improved quality of life due to better treatment options. The research may, one day, pave the way to finding a cure for the condition.

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