Congenital Myasthenic Syndrome-4C in a Consanguineous Romani Family: Genetic Insights and Clinical Implications

Background and Clinical Significance: Congenital myasthenic syndrome-4C (CMS4C) associated with acetylcholine receptor (AChR) deficiency is an autosomal recessive defect of the motor endplate caused by homozygous or compound heterozygous mutations in the CHRNE gene on chromosome 17p13. Case Presentation: The authors present a familial case of CMS4C with three affected children in a consanguineous Romani family. Muscle weakness, fatigue, and ocular muscle impairment were present in all cases; two of the three siblings had delayed motor milestones, highly arched palates, and facial weakness. None of the children expressed bulbar symptoms. One child expressed a severe form, with recurrent respiratory infections, and multiple hospitalizations, while the other siblings expressed a mild phenotype, without hospital admissions. Repetitive nerve stimulation showed a myasthenic-type decrement greater than 10% of several muscles. A pathogenic frameshift variant (NM_000080.4: c.1327del) in the CHRNE gene was found in a homozygous status in all the affected children and in both parents. After 6 months of Pyridostigmine and Salbutamol treatment, the evolution of the case was good, with the improvement of most of the signs and no need for hospitalization. Conclusions: Early genetic diagnosis and appropriate therapy in the context of a multidisciplinary approach is mandatory for an optimal long-term prognosis. Community-wide carrier screening through comprehensive genetic testing is imperative to ensure accurate genetic counseling in genetic isolates. The authors report this case due to the increased number of affected children in a consanguine family from a small Romani community.