So Okubo

Pathogenic DMD variants usually follow the reading‐frame rule: out‐of‐frame changes cause Duchenne muscular dystrophy, whereas in‐frame ones produce Becker muscular dystrophy (BMD). We report a 23‐year‐old man with BMD‐like weakness, calf hypertrophy, elevated creatine kinase, and dilated cardiomyopathy. A novel hemizygous c.2281delG variant converted an A₄GA₅ motif to A₉, predicting a frameshift; however, Western blot showed ~15% full‐length dystrophin. cDNA and polymerse chain reaction (PCR)‐free direct RNA sequencing demonstrated transcriptional slippage, adding 1 adenine (A₁₀) that restores the reading frame and dystrophin. This RNA‐level rescue of an out‐of‐frame DMD variant explains the mild phenotype and highlights the importance of transcript‐level analysis in dystrophinopathies. ANN NEUROL 2026;99:223–230

PLA2G6-associated neurodegeneration (PLAN) encompasses a spectrum of phenotypes caused by biallelic pathogenic variants in PLA2G6. Initially linked to infantile and atypical neuroaxonal dystrophy, PLAN now includes adult-onset conditions such as dystonia-parkinsonism, ataxia, and spastic paraplegia. We report a female patient presenting young-onset parkinsonism with pyramidal tract signs, cerebellar atrophy, and autonomic dysfunction, mimicking multiple system atrophy (MSA). Neuroimaging showed decreased dopamine uptake and cerebellar hypoperfusion. Genetic analysis identified a homozygous pathogenic variant in PLA2G6 (c.967G>A, p.Val323Met), confirming a diagnosis of PLAN. Interestingly, elevated serum autotaxin levels (4.67 ng/mL) without liver abnormalities. Bilateral brachymetatarsia was also observed, which may indicate an association with the PLA2G6 variant. This case underscores the importance of considering PLAN in cases of young-onset parkinsonism with multisystem involvement. Genetic testing is crucial for accurate diagnosis and management of such cases. Elevated serum autotaxin levels may be associated with decreased phospholipase activity in PLAN and warrants further investigation.

Background: Dropped head syndrome (DHS) is a group of disorders that result in anterior neck flexion. Myasthenia gravis (MG) is a common cause of DHS. Previous reports have suggested that concurrent myopathy involving the paraspinal musculature may underlie DHS in patients with anti‐acetylcholine receptor antibody‐positive or thymoma‐associated MG.Case Presentation: A 64‐year‐old woman presented with a 3‐month history of head drop and lordosis. Neurological examination revealed bilateral ptosis and weakness of the posterior neck extensors. Electrophysiology suggested neuromuscular junction involvement. Serum anti‐MuSK antibodies were positive, and generalized anti‐MuSK antibody‐positive myasthenia gravis (MuSK‐MG) was diagnosed. Needle electromyography (nEMG) of the splenius capitus and paraspinal muscles revealed acute and chronic myogenic changes. Imaging suggested paraspinal muscle atrophy. nEMG and magnetic resonance imaging (MRI) of both extremities were normal, and autoimmune myopathy‐related antibody testing was negative.Conclusion: Thymoma‐negative MuSK‐MG, demonstrating treatment‐refractory DHS, may present with concurrent axial myopathy.