The patient presented with arthrogryposis, diffuse edema, and respiratory failure, suggestive of fetal akinesia, and required mechanical ventilation. Fetal akinesia deformation sequence results from defects at any point in the neuromuscular pathway from brain to spinal cord, motor neuron, neuromuscular junction, or skeletal muscle and connective tissue. Although most cases go undiagnosed, targeted therapies may be available if the cause is identified.  Some of these include the congenital myasthenia syndromes, a group of genetic disorders caused by changes in the neuromuscular junction.  Treatment varies depending on type.

Trio exome sequencing was performed using the Agilent Clinical Research Exome kit. Bidirectional sequence was assembled and aligned to the human reference genome and analyzed for sequence variants using a custom developed analysis tool (Xome Analyzer) as part of the Seattle Children’s Rapid Inpatient Genomic Testing (RIGhT) project. Nerve conduction studies and slow repetitive nerve stimulation of the right median nerve were performed before and after pyridostigmine administration. This was compared to a control case.

The patient had biallelic pathogenic variants in CHRNB1, conferring pyridostigmine-responsive congenital myasthenia syndrome, receptor-deficiency subtype. Genetic diagnosis combined with nerve conduction studies confirmed the genotype-phenotype association, excluded a slow-channel syndrome, and facilitated targeted treatment of the proband. The patient gained some movement and was extubated following treatment.