NALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia, and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. We present a patient in whom congenital myasthenic syndrome (CMS) was suspected due to the occurrence of hypotonia and apnea episodes requiring resuscitation. For this reason, treatment with pyridostigmine was introduced. After starting the treatment, a significant improvement was observed in reducing the apnea episodes and slight psychomotor progress. In the course of further diagnostics, CMS was excluded, and CLIFAHDD syndrome was confirmed. Thus, we try to explain a possible mechanism of clinical improvement after the introduction of treatment with pyridostigmine in a patient with a mutation in the NALCN gene.
An 81-year-old woman presented with neck weakness, dysarthria, dysphasia and left-sided ptosis. Myasthenia gravis (MG) was strongly suspected. Voltage gated calcium channel (VGCC) antibodies, associated with Lambert-Eaton myasthenic syndrome (LEMS), were negative. Acetylcholine receptor (AChR) antibody level was 536 nmol/L and diagnosis of MG was confirmed. Imaging revealed a pelvic mass and subsequent biopsy confirmed a pelvic follicular lymphoma. Our searches revealed this to be the first documented case of MG associated with a pelvic follicular lymphoma. She underwent radiotherapy to treat the lymphoma and received both pyridostigmine and immunosuppression to treat the MG. Her AChR antibody level decreased to 38 nmol/L and her MG symptoms resolved aside from head drop which is continuing to improve. Her lymphoma is now in remission. We have presented a case with a successful outcome, which highlights the importance of screening for lymphoma and thymoma in new presentations of MG.
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.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes.  The initial presentation can be similar to that of myasthenia gravis (MG), but the progressions of the 2 diseases have some important differences. LEMS disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca2+ channels involved with neurotransmitter release.