Homozygous AGRN mutation manifesting as limb girdle weakness and respiratory failure

<h3></h3> The patient is a 36-year-old, right-handed housewife. She has a personal and family history significant for multigenerational consanguinity. She presented with a 12-year history of lower limb weakness with neither bulbar symptoms nor fatigability. She is one of three siblings affected. She came to the attention of neurology services after developing type 2 respiratory failure, necessitating admission to hospital and urgent commencement of non-invasive ventilation. Nerve conduction studies and EMG were performed, which showed clinically significant decrement in compound muscle action potentials of bilateral abductor pollicis brevis (13.7–23.8%) muscles, the right trapezius (12.9%) and right extensor digitorum brevis (up to 32.6%) and mild myopathic changes. Overall, despite the lack of cranial nerve signs and fatigable weakness, the presentation was felt to be in keeping with a congenital myasthenic syndrome (CMS). Genetic testing revealed homozygosity for variants in the AGRN gene, a rare cause of CMS. She has been started on salbutamol, and her pre-treatment MG-ADL and MG composite scores were 7 and 16 respectively. This case enriches the known phenotypic spectrum of CMS. Given their treatable nature, it is important to have a high index of suspicion for such disorders, even in patients without typical myasthenic symptoms.