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We genetically evaluated 260 dystrophinopathy patients from Turkey. Karyotyping as an initial test in female patients, followed stepwise by multiplex ligation-dependent probe amplification and by targeted next-generation sequencing of DMD revealed definitive genetic diagnoses in 214 patients (82%), with gross deletions/duplications in 153 (59%), pathogenic sequence variants in 60 (23%), and X-autosome translocation in one. Seven of the gross and 27 of the sequence variants found novel. In silico prediction, co-segregation and transcript assays supported the pathogenic nature of the novel silent (p.Lys534=) and the splice site (c.4345-12C>G) alterations. From a total of 189 singleton cases, 154 (82%) had pathogenic alterations. From 138 of those who had maternal carrier testing, 68 out of 103 (66%) showed gross and 11 out of 35 (31%) showed small pathogenic variants. This suggests that the de novo occurrences in DMD appear approximately 2.1 times more frequently in meiotic unequal crossing-over than in uncorrected replication errors. Our study also disclosed three mothers as obligate gonadal mosaic carriers. Family-based investigation of dystrophinopathy patients is crucial for the ascertainment of novel or rare variants and also for counseling and follow-up care of the families.

Background Scapulothoracic arthrodesis (STA) is a well-established surgical technique to provide scapular stabilization in patients with facioscapulohumeral dystrophy (FSHD). There is no staging or scoring systems available to guide surgical decision. The aim of this study was to develop a staging system to evaluate the shoulder disability in patients with FSHD to guide surgical decision making and assess its reliability among surgeons. Methods Fifty-seven shoulders of 29 patients (15 male, 14 female) with an average age of 34.5 years (13–73) were included. Six stages of the disease were defined to create a system consisting of shoulder elevation, deltoid function and scapular winging. Patients were assessed by two independent orthopaedic surgeons who were blind to each other. Statistical analyses included mean and standard deviation for descriptive variables, Pearson's correlation and Cohen's Kappa for inter and intra observer agreement. Results Measurement of elevation showed excellent correlation in both inter- and intraobserver assessment. There was substantial agreement on deltoid function and moderate agreement on scapular winging. Decision on stage showed excellent agreement on inter observer and substantial agreement on intra observer assessment. Surgical decision using the stage showed excellent agreement on both inter and intra observer assessment. Conclusion This novel staging system has an excellent inter observer agreement on FSHD patients’ shoulder disability. This would provide surgeons a beneficial tool to define patient groups that would have negatively or positively affected from STA.

Anti-MuSK positive myasthenia gravis (MuSK-MG) is rare prepuberty. We report a female patient with MuSK-MG starting at 3.5 years with ptosis as the sole symptom for 2 years. A brief period of generalization was followed by complete stable remission for 6 years. Prolonged ocular symptoms and long remissions are not features of MuSK-MG, but are often seen in prepubertal onset MG. The patient then presented at age 12 with moderately severe symptoms which were almost confined to oculobulbar muscles and were unresponsive to pyridostigmine. She was dependent on corticosteroids and thymectomy did not seem to be effective. She was later noted to have tongue atrophy after a period without treatment. Our patient thus presented with features seen in many prepubertal patients, but the later course was quite typical of MuSK-MG.

PubMedID: 19285864 An 11-year-old girl with a calpain-3 gene (CAPN-3) mutation and eosinophilic myositis on muscle biopsy had high serum CK levels and eosinophil counts which showed spontaneous fluctuations. After commencement of immunosuppressive therapy reciprocal changes occured in response to alterations in doses of the medications. Subacutely evolving and spreading muscle weakness developed during tapering of the immunosuppressive medications. These observations suggest that either the occurrence of eosinophilic myositis or the withdrawal of the immunosuppressive treatment may have accelerated the clinical course of the calpainopathy in this case. The positive effect of immunosuppressive therapy might have implications for the management of calpainopathy with an inflammatory component. © 2009 Elsevier B.V. All rights reserved.

Oculopharyngodistal myopathy (OPDM) is a rare, adult-onset, slowly progressive hereditary vacuolar myopathy in which the weakness and atrophy affect oculofacial, pharyngeal and distal skeletal muscles. The underlying genetic defect is yet unknown. Swallowing difficulties and hoarseness due to oropharyngeal involvement are two of the most prominent features of the condition affecting the quality of life and survival of the patients. Swallowing difficulty due to cord paresis and atrophy causes aspiration, compromises respiration and cause premature death. Vocal fold injection augmentation with different types of materials is a method used to treat vocal cord paralysis, paresis, atrophy and scars. It is a safe, repeatable, practical and effective procedure and can be performed in awake patients or under general anesthesia. Here, we report the dramatic outcome after vocal cord injection augmentation in a 43 years old female patient with OPDM, evidenced by improvement in ENT examination, videolaryngostroboscopic evaluation, Voice Handicap Index (Validated in Turkish), MDVP Analysis, M.D. Anderson Dysphagia Inventory, FEES (Fiberoptic Endoscopic Evaluation of Swallowing). We examined the patient, and performed all the tests during preoperative and postoperative 1st week, 1st month and 3rd month visits. No complications occurred during or after the procedure. The method was very successful in that aspirations stopped immediately after the injection, the voice became less hoarse and speech was more understandable. Augmentation was more effective for aspiration than for voice quality. Oculopharyngodistal myopathy is a non-curable genetic disease which threatens life due to respiratory insufficiency even in ambulatory patients. Application of vocal cord injection augmentation can be a promising symptomatic therapy option to decrease or stop aspiration in patients with OPDM. A larger study with more patients and longer follow-up is ongoing.

Findings in recent epidemiological studies have implied that the frequency of myasthenia gravis (MG) may be increasing in the elderly population. Published studies of late-onset MG have disclosed some of its characteristics: males are more frequently affected, the thymus is more likely to be involuted, there is a different HLA profile and anti-striatal muscle antibodies against titin/ryanodine receptors may be present. In our MG database, there were 95 generalized non-thymomatous MG patients with disease onset ⩾50 years who first presented to our outpatient clinic during the 10 years between 2001 and 2010 and who were followed for at least 3 years. All patients were contacted by phone calls or letters. There was a marked male preponderance with male to female ratio of 1.7:1. Onset was with predominantly ocular symptoms (62%), followed by bulbar symptoms (23%) and weakness in the extremities (11%); two patients had neck weakness and 4 had mixed onset symptoms. Anti-acetylcholine receptor antibodies (AChR Ab) were present in 84%, 5% were anti-MuSK Ab positive and 11 % were double negative. Sixty-two percent had anti-titin antibodies. The disease was mild (MGFA 2) in approximately half of the patients (47%) while 6% were intubated. Fifty-seven percent (including all of the patients with MuSK MG) had MGFA postintervention status of complete stable remission/pharmacological remission/minimal manifestations at the last visit. A further 28 % were improved. The combination of prednisolone and azathioprine appeared to be superior to these agents used alone. In 15 mildly affected patients in whom azathioprine was combined with low dose prednisolone (