Nemaline myopathy with stiffness and hypertonia associated with an ACTA1 mutation

Abstract

Nemaline myopathy, known to be caused by mutations in 7 genes, including skeletal muscle α-actin ( ACTA1 ),1 is characterized by muscle weakness, hypotonia, and nemaline rods in muscle biopsy. Here we report a patient with nemaline rods but the opposite phenotype of hypercontractility. ### Case report. The John Radcliffe Hospital ethics review board approved the study. The first child of nonconsanguineous European parents presented at 6 weeks of age with an apneic episode thought due to bilateral strangulated inguinal hernias and an umbilical hernia. However, after herniotomy, rigidity and recurrent apneas requiring mechanical ventilation continued. The patient was born by elective Caesarean section at 39 weeks, with no perinatal complications, although the mother, with hindsight, thought there might have been stiffness in the weeks after birth as she had difficulty clothing him. Polyhydramnios had been noted. On examination, he had very stiff and hypertrophic abdominal and proximal limb muscles and elbow and knee contractures. Deep tendon reflexes showed brisk contraction and slow relaxation and percussion myotonia could be elicited. However, EMG in multiple muscles showed no evidence of myotonia. He also had normal nerve conduction studies, MRI, EEG, and cardiac assessment, including echocardiography. Neurometabolic investigations were also normal including serum and CSF lactate, CSF neurotransmitters, urinary catecholamines, carnitine profile, white cell enzymes, and screening for mucopolysaccharidosis. Serum creatine kinase was slightly raised (370 IU, range 24–195). A sleep study showed hypoventilation and carbon dioxide retention. Hyperekplexia, paroxysmal episodic pain disorder, neuromyotonia, and episodic ataxia were considered, though none exactly matched the phenotype because of the underlying stiffness, but relevant testing ( ARX , FRAXA , GLRA1 , KCN1A , POLG , SCN9A , anti GAD, and VGKC antibody studies) was negative. Pharmacologic treatment including phenytoin, carbamazepine, flecainide, baclofen, dantrolene, and acetazolamide was ineffective. He continued having recurrent episodes of stiffness, where he stopped …