Paraspinal amyotrophy in DNM-2-related centronuclear myopathy CURRENT STATUS:

Background Dynamin 2-related centronuclear myopathy (DNM2-CNM) is a rare congenital myopathy, and clinically, slowly progressive muscle weakness in the distal or proximal limbs, calf muscle atrophy, and pes cavus are features that are highly suggestive of DNM2-CNM. We experienced a case of DNM2-CNM who exhibited marked paraspinal amyotrophy on CT and showed a mutation in the GTPase effector domain (GED) of DNM2. Case presentation A 50-year-old man presented with a 5-year history of lumbar pain and slow progression of foot weakness. He showed bilateral pes cavus. Electromyography revealed a myopathic pattern, and nerve condition velocities and amplitudes were normal. Muscle CT showed marked fat replacement in the posterior compartment of the lower extremities, and also demonstrated severe involvement of the erector spinae muscles. Muscle biopsy from quadriceps femoris showed nuclear centralization in the majority of fibers. Sequence analysis of Dynamin 2 (DNM-2) demonstrated heterozygous c.1948G>A (p.E650 K) mutation compatible with the diagnosis of DNM2-CNM. Conclusions This case suggests that marked paraspinal amyotrophy may be a characteristic feature of DNM2-CNM. The selective involvement of the erector spinae muscles and posterior compartment of the lower extremities could offer a valuable feature for the diagnosis of DNM2-CNM.

year history of lumbar pain and slow progression of foot weakness. He showed bilateral pes cavus.

Background
Centronuclear myopathy (CNM) is a rare congenital myopathy characterized by the morphological feature of centrally located nuclei in a large number of muscle fibers. CNM is related to several causative genes: dynamin 2 (DNM2), myotubularin (MTM1), amphiphysin 2 (BIN1), and ryanodine receptor 1 (RYR1) [1]. DNM2-related CNM (DNM2-CNM) is an autosomal-dominant inherited disease that accounts for about 50% of CNM cases [1]. Although DNM2-CNM has shown a variety of clinical manifestations, from severe neonatal onset to mild adult onset, most patients present with slowly progressive muscle weakness in the distal or proximal limbs, ptosis, ophthalmoplegia, and facial weakness [2,3]. Muscle imaging, computed tomography (CT) and magnetic resonance imaging (MRI), studies have clearly shown relatively diffuse involvement in the lower leg muscles, but a selective pattern of involvement in posterior compartment muscles like gastrocnemius, soleus, biceps femoris, 3 and semimembranosus [2][3][4]. Proximal limb girdle and paraspinal muscles could be affected clinically.
However, no reports have evaluated muscle involvements other than of the upper and lower extremities using CT or MRI. Herein, we report a case of CNM with a DNM2 mutation (p.E650 K) that demonstrated marked erector spinae muscle atrophy on CT.

Case Presentation
A 50-year-old Japanese man noticed grip weakness in his 20s. He presented with a 5-year history of lumbar pain, flexed posture, easy fatigability, and slow progression of foot weakness. No family history of neuromuscular disorders was elicited. On admission, neurological examination showed slight muscle weakness and atrophy in the distal lower extremities. He also exhibited pes cavus due to plantar muscle atrophy (Fig. 1a). However, the patient was independent in terms of daily activities.
He did not have ptosis or ophthalmoplegia. Serum creatine kinase level was 150 IU/L.
Electromyography revealed a myopathic pattern without neuropathic signs, and nerve condition velocities and amplitudes were normal. Muscle CT showed marked fat replacement in the posterior compartment of the lower extremities (biceps femoris, semitendinosus, semimembranosus, gastrocnemius and soleus), while the quadriceps femoris and adductor magnus muscles were less affected (Fig. 1b,c). Muscle CT also demonstrated severe involvement of the erector spinae muscles (iliocostalis, longissimus and spinalis) (Fig. 1e-g), and moderate atrophy and fatty changes were observed in the gluteus maximus (Fig. 1g). Hematoxylin and eosin staining of a muscle biopsy from the quadriceps femoris showed nuclear centralization in 60% of fibers (Fig. d), and radial distributions of sarcoplasmic strands were observed on NADH-TR (data not shown). Genetic analysis identified heterozygous c.1948G>A (p.E650 K) mutation in the DNM2 GTPase effector domain, representing a previously reported mutation [5].

Discussion
We report a case of DNM2-CNM in a patient who exhibited marked paraspinal amyotrophy on CT and showed a mutation in the GTPase effector domain (GED) of DNM2. Muscle CT in this case showed severe atrophy in the posterior compartment of the lower extremities (biceps femoris, semitendinosus, semimembranosus, gastrocnemius and soleus), and this selective pattern of muscle involvement was compatible with the findings of previous reports [2][3][4]. Our case also revealed a characteristic feature of marked paraspinal amyotrophy. No previous reports have described the appearance of paraspinal muscles on CT or MRI. However, since some cases showed muscle atrophy in the gluteus maximus [4], marked atrophy in not only the posterior compartment of the lower extremities, but also the trunk could offer a valuable feature for the diagnosis of DNM2-CNM. to more serious clinical manifestations [5]. Our case showed slowly progressive moderate myopathy compatible with the clinical features of a previously reported case with the same GED mutation [5].
This GED mutation leads to relatively mild clinical features compared to those of CNM patients with the two majority mutations in the MD and PH domains. In addition, the marked paraspinal atrophy may represent a unique feature of DNM2-CNM harboring the GED mutation.
However, the patient in our case revealed neither symptom. A previous study indicated that ptosis and ophthalmoplegia are comparatively rare among Japanese patients, and ethnic background or genetic factors may contribute this finding [5].