Surgical treatment of dropped head syndrome secondary to fascioscapulohumeral muscle dystrophy: a case report

Fascioscapulohumeral muscular dystrophy is an uncommon hereditary myopathy which affects mainly the muscle of the face and upper limb girdle. We present a rare case with dropped head syndrome as the prominent manifestation of that disease and successfully treated by surgical management. It was a 25-year-old male patient with the chief complaint of neck pain and inability to maintain his horizontal gaze for long periods and as a result he had to quit his job as a shipper. His mother also had signs and symptoms of fascioscapulohumeral muscle dystrophy. Conservative treatment consisting of physical therapy and hard collar was the first attempt in order to reduce the neck pain and had limited result. We then performed a posterior cervical surgery including C2 to T2 instrumentation and kyphotic correction for the patient. The ten-month postop clinical and radiological results were satisfactory and the patient could return to his previous job. Dropped head syndrome with failed conservative treatment can be surgically treated after considering all clinical and radiographic factors.

Dynamin-2 Phosphorylation as A Critical Regulatory Target of Bin1 and GSK3α for Endocytosis in Muscle

Tight regulation of endocytosis ensures accurate control of cellular signaling and membrane dynamics, which are crucial for tissue morphogenesis and functions. Mutations of Bin1 and dynamin-2 (Dyn2), proteins that generate membrane curvature and sever endocytic invaginations, respectively, cause progressive hereditary myopathy. Here, we show that Bin1 inhibits Dyn2 via direct interaction of its SRC Homology 3 (SH3) domain with the proline-rich domain (PRD) of Dyn2. Phosphorylation of S848 of Dyn2 by GSK3α, a kinase downstream of insulin signaling, relieves Dyn2 from the inhibition of Bin1 and promotes endocytosis in muscle. Mutations of Bin1 associated with centronuclear myopathy disrupt its inhibition of Dyn2, thereby exaggerating Dyn2 fission activity and causing excessive fragmentation of T-tubules in the muscle cells. Our work reveals how Bin1-Dyn2 interaction fine-tunes membrane remodeling at the molecular level, and lay the foundation for future exploration of endocytic regulation and hereditary muscle diseases.

Expanding the Clinico-Genetic Spectrum of Myofibrillar Myopathy: Experience From a Chinese Neuromuscular Center

Background: Myofibrillar myopathy is a group of hereditary neuromuscular disorders characterized by dissolution of myofibrils and abnormal intracellular accumulation of Z disc-related proteins. We aimed to characterize the clinical, physiological, pathohistological, and genetic features of Chinese myofibrillar myopathy patients from a single neuromuscular center.Methods: A total of 18 patients were enrolled. Demographic and clinical data were collected. Laboratory investigations, electromyography, and cardiac evaluation was performed. Routine and immunohistochemistry stainings against desmin, αB-crystallin, and BAG3 of muscle specimen were carried out. Finally, next-generation sequencing panel array for genes associated with hereditary neuromuscular disorders were performed.Results: Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations. The novel DES c.1256C>T substitution is a high frequency mutation. The combined recessively/dominantly transmitted c.19993G>T and c.107545delG mutations in TTN gene cause a limb girdle muscular dystrophy phenotype with the classical myofibrillar myopathy histological changes.Conclusions: We report for the first time that hereditary myopathy with early respiratory failure patient can have peripheral nerve and severe spine involvement. The mutation in Ig-like domain 16 of FLNC is associated with the limb girdle type of filaminopathy, and the mutation in Ig-like domain 18 with distal myopathy type. These findings expand the phenotypic and genotypic correlation spectrum of myofibrillar myopathy.

Titinopathy, an atypical respiratory failure

Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation.

Hereditary Myopathy with Early Respiratory Failure with a Heterozygous TTN Gene Missense Mutation

Hereditary myopathy with early respiratory failure (HMERF) is characterized by early respiratory insufficiency which is inappropriate to the degree of limb muscle weakness. Recently, mutation in <i>TTN</i> gene was found in HMERF patients with the aid of gene sequencing. We describe the first case presenting with distal leg weakness and early respiratory failure confirmed by <i>TTN</i> gene mutation in Korea.