Centronuclear myopathy related to dynamin 2 mutations: Clinical, morphological, muscle imaging and genetic features of an Italian cohort

Abstract

Mutations in dynamin 2 (DNM2) gene cause autosomal dominant centronuclear myopathy and occur in around 50% of patients with centronuclear myopathy. We report clinical, morphological, muscle imaging and genetic data of 10 unrelated Italian patients with centronuclear myopathy related to DNM2 mutations. Our results confirm the clinical heterogeneity of this disease, underlining some peculiar clinical features, such as severe pulmonary impairment and jaw contracture that should be considered in the clinical follow-up of these patients. Muscle MRI showed a distinct pattern of involvement, with predominant involvement of soleus and tibialis anterior in the lower leg muscles, followed by hamstring muscles and adductor magnus at thigh level and gluteus maximus. The detection of three novel DNM2 mutations and the first case of somatic mosaicism further expand the genetic spectrum of the disease.

Congenital myopathies

“…4 The natural history of specific subgroups has been described in only a few cohorts, not all of which had been fully genetically characterized. 5,[13][14][15][16][17][18][19] Herein, we report the clinical course of 125 patients with CM, reviewed at a single neuromuscular center. Furthermore, genotypephenotype correlations in a subgroup of 99 genetically characterized cases are illustrated.…”

Clinical Reasoning: A 51-year-old woman with weakness and stiff neck

“…8 Severe infantile forms can occur. 3,7 Children often have delayed motor milestones, along with limb and facial weakness, and associated atrophy. Ophthalmoparesis and ptosis are common.…”

“…Ophthalmoparesis and ptosis are common. 3 Skeletal abnormalities include scoliosis and pes cavus; RSS is a rarely reported manifestation. Cardiac abnormalities are exceedingly infrequent, but many patients can have restrictive lung disease.…”

“…Cardiac abnormalities are exceedingly infrequent, but many patients can have restrictive lung disease. 3 Adult-onset forms are usually milder. Muscle biopsy tends to show a triad of (1) nuclear centralization, (2) radiating sarcoplasmic strands easily recognizable in NADH-TR-stained transverse sections, and (3) type 1 fiber preponderance and smallness.…”

“…(Medical Research Council [MRC] grade 2-3) and milder proximal more than distal upper limb weakness (MRC grade [3][4]. The weakness was relatively symmetric (right minimally worse than left).…”