scholarly journals Late presented congenital myasthenic syndrome with novel compound heterozygous CHRNE mutations mimicking seronegative myasthenia gravis

2019 ◽  
Vol 7 (5) ◽  
pp. 288-290
Author(s):  
Yumiko Nakano ◽  
Keiichiro Tsunoda ◽  
Toru Yamashita ◽  
Jun Mitsui ◽  
Kota Sato ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Seronegative Myasthenia Gravis ◽  
Myasthenic Syndrome

scholarly journals Congenital myasthenic syndrome in a cohort of patients with ‘double’ seronegative myasthenia gravis

2021 ◽  
Author(s):  
Paulo José Lorenzoni ◽  
Renata Dal-Pra Ducci ◽  
Raquel Cristina Arndt ◽  
Nyvia Milicio Coblinski Hrysay ◽  
Otto Jesus Hernandez Fustes ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Myasthenia Gravis ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Previous Diagnosis ◽  
Seronegative Myasthenia Gravis ◽  
Single Center Study ◽  
Myasthenic Syndrome ◽  
Compound Heterozygous Variants ◽  
Brazilian Cohort

ABSTRACT Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. Results: We performed genetic analysis in 22 patients with a previous diagnosis of ‘double’ SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in ‘double’ SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with ‘double’ SNMG in whom differential diagnosis is recommended.

Ophthalmoplegia

2015 ◽  
Author(s):  
Aziz Shaibani
Keyword(s):  
Family History ◽  
Muscular Dystrophy ◽  
Myasthenia Gravis ◽  
Eye Movement ◽  
Congenital Myasthenic Syndrome ◽  
Oculopharyngeal Muscular Dystrophy ◽  
Detailed Family History ◽  
Myasthenic Syndrome ◽  
The Brain

Ophthalmoplegia is usually chronic and therefore diplopia is not a feature. There is enough time for the brain to suppress one image. It is amazing how much impairment of eye movement has to occur before the patient becomes concerned or considers it as abnormal. Neglected myasthenia gravis may be confused with mitochondrial ophthalmoplegia or oculopharyngeal muscular dystrophy or even congenital myasthenic syndrome. Central cause of ophthalmoplegia should be ruled out first by performing doll’s eye movement. Detailed family history looking in particular for ptosis, ophthalmoplegia, and dysphagia is diagnostically very useful. Non neurological causes of ophthalmoplegia such as severe exophthalmus, and retroorbital pathology should be considered.

Ophthalmoplegia

2018 ◽  
Author(s):  
Aziz Shaibani
Keyword(s):  
Muscular Dystrophy ◽  
Myasthenia Gravis ◽  
Eye Movement ◽  
Congenital Myasthenic Syndrome ◽  
Oculopharyngeal Muscular Dystrophy ◽  
Laboratory Methods ◽  
Different Types ◽  
Myasthenic Syndrome ◽  
The Brain

Ophthalmoplegia is usually chronic, and therefore diplopia is not a feature. There is enough time for the brain to suppress one image. It is amazing how much of impairment of eye movement has to occur before the patient becomes concerned or considers it as abnormal. Neglected myasthenia gravis (MG) may be confused with mitochondrial ophthalmoplegia or oculopharyngeal muscular dystrophy (OPMD) or even congenital myasthenic syndrome (CMS). Central causes of ophthalmoplegia should be ruled out first by performing doll’s eye movement. A number of cases of different types of ophthalmoplegia are presented, along with clinical and laboratory methods to differentiate them.

scholarly journals Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

2016 ◽  
Vol 26 (4) ◽  
Author(s):  
Andreas Totzeck ◽  
Petra Mummel ◽  
Oliver Kastrup ◽  
Tim Hagenacker
Keyword(s):  
Myasthenia Gravis ◽  
Calcium Channel ◽  
Muscle Weakness ◽  
Neuromuscular Disorders ◽  
Intravenous Immunoglobulins ◽  
Voltage Gated ◽  
Dropped Head Syndrome ◽  
Seronegative Myasthenia Gravis ◽  
Myasthenic Syndrome ◽  
Voltage Gated Calcium Channel

Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

098 A case of myasthenia gravis lambert eaton overlap syndrome (MLOS) in seronegative myasthenia gravis

2018 ◽  
Vol 89 (6) ◽  
pp. A39.1-A39
Author(s):  
Sameer Saleem ◽  
Ronak Patel ◽  
Yash Gawarikar
Keyword(s):  
Myasthenia Gravis ◽  
Calcium Channel ◽  
Overlap Syndrome ◽  
Initial Examination ◽  
Blurred Vision ◽  
Voltage Dependent Calcium Channel ◽  
Seronegative Myasthenia Gravis ◽  
Voltage Dependent ◽  
Myasthenic Syndrome ◽  
Seronegative Mg

IntroductionMyasthenia gravis (MG) is an antibody-mediated autoimmune disease of neuromuscular transmission. 6 to 12 percent of MG are negative for acetyl choline receptor (AChR) and MuSK antibodies and are defined as seronegative MG. Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune condition with antibodies to presynaptic voltage-dependent calcium channelCaseA 39 year old male presented with blurred vision and right-sided ptosis. Initial examination showed a pupil-sparing left complete third nerve palsy. Demyelination and intracranial aneurysms were ruled out with gadolinium-enhanced MRI/MRA. Outpatient follow-up 2 weeks later showed new onset proximal muscle weakness of the upper limbs with fatigability and a complex ophthalmoplegia with almost complete paralysis of gaze. A repeat MRI with gadolinium and CSF analysis were normal. His AChR and MuSK antibodies were negative; however, voltage-dependent calcium channel antibodies, ANA, dsDNA, and SSA were positive. Initial nerve conduction tests were normal, but repeat NCS on two separate occasions showed decrement on repetitive stimulation in the right trapezius with no evidence of facilitation post exercise. CT chest, abdomen and pelvis was normal. He improved with pulsed steroids and was discharged on a tapering dose of oral steroids, pyridostigmine and regular IVIG infusions as a steroid-sparing agent.ConclusionLambert-Eaton myasthenic syndrome shares the same pathologic site and similar pathophysiology with MG but has a markedly different clinical and electro-physiological picture. There are reports of MG and LEMS overlap syndrome, however, they exhibit phenotypic characteristics of both LEMS and MG. Voltage-dependent calcium channel antibodies have not been described in patients with seronegative MG. Ours is potentially the first reported case of seronegative myasthenia with voltage-dependent calcium channel antibodies and only clinical and neurophysiological features of MG.

scholarly journals A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 821
Author(s):  
Olga Shchagina ◽  
Ludmila Bessonova ◽  
Igor Bychkov ◽  
Tatiana Beskorovainaya ◽  
Aleksander Poliakov
Keyword(s):  
Uniparental Disomy ◽  
Missense Variant ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Chromosome 2 ◽  
Loss Of Function ◽  
Maternal Uniparental Disomy ◽  
Healthy Sibling ◽  
Myasthenic Syndrome ◽  
The Moment

Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA samples of five family members: two patients with myasthenia, their healthy sibling and parents. Clinical exome analysis was carried out for one patient, then the whole family was checked for target variants with Sanger sequencing, quantitative multiplex ligation-dependent probe amplification, and chromosome 2 microsatellite markers study. To determine the functional significance of the splicing variant, we applied the minigene assay. The cause of the proband’s disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second patient’s disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2. In this study, we describe a unique case, in which two siblings with a rare disorder have different pathologic genotypes.

scholarly journals CHRNE compound heterozygous mutations in congenital myasthenic syndrome

Medicine ◽  
2018 ◽  
Vol 97 (17) ◽  
pp. e0347
Author(s):  
Kunfang Yang ◽  
Hongyi Cheng ◽  
Fang Yuan ◽  
Linyi Meng ◽  
Rongrong Yin ◽  
...  
Keyword(s):  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Myasthenic Syndrome ◽  
Compound Heterozygous Mutations
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