Valosin-containing protein-related myopathy and Meige syndrome : Just a coincidence or not?

Non peer reviewe

Editorial : Current and Future Developments in the Therapeutic Management of Neuromuscular Diseases

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Mild myopathic phenotype in a patient with homozygous c.416C > T mutation in TK2 gene

The mitochondrial DNA depletion syndrome (MDDS) is characterized by extensive phenotypic variability and is due to nuclear gene mutations resulting in reduced mtDNA copy number. Thymidine kinase 2 (TK2) mutations are well known to be associated with MDDS. Few severely affected cases carrying the c.416C > T mutation in TK2 gene have been described so far. We describe the case of a 14months boy with the aforementioned TK2 gene pathogenic mutation at a homozygous state, presenting with a mild clinical phenotype. In addition to severe mitochondrial pathology on muscle biopsy, there was also histochemical evidence of adenylate deaminase deficiency. Overall, this report serves to further expand the clinical spectrum of TK2 mutations associated with MDDS

Adult-onset dominant muscular dystrophy in Greek families caused by Annexin A11

Objective: Mutations in the prion-like domain of RNA binding proteins cause dysfunctional stress responses and associated aggregate pathology in patients with neurogenic and myopathic phenotypes. Recently, mutations in ANXA11 have been reported in patients with amyotrophic lateral sclerosis and multisystem proteinopathy. Here we studied families with an autosomal dominant muscle disease caused by ANXA11:c.118G > T;p.D40Y. Methods: We performed deep phenotyping and exome sequencing of patients from four large Greek families, including seven affected individuals with progressive muscle disease but no family history of multi-organ involvement or ALS. Results: In our study, all patients presented with an autosomal dominant muscular dystrophy without any Paget disease of bone nor signs of frontotemporal dementia or Parkinson's disease. Histopathological analysis showed rimmed vacuoles with annexin All accumulations. Electron microscopy analysis showed myofibrillar abnormalities with disorganization of the sarcomeric structure and Z-disc dissolution, and subsarcolemmal autophagic material with myeloid formations. Molecular genetic analysis revealed ANXA11:c.118G > T;p.D4OY segregating with the phenotype. Interpretation: Although the pathogenic mechanisms associated with p.D4OY mutation in the prion-like domain of Annexin All need to be further clarified, our study provides robust and clear genetic evidence to support the expansion of the phenotypic spectrum of ANXA11.Peer reviewe

Toward understanding tissue-specific symptoms in dolichol-phosphate-mannose synthesis disorders; insight from DPM3-CDG

Contains fulltext : 208143.pdf (publisher's version ) (Open Access

â-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek population

ABSTRACT â-thalassemia (â-thal) is characterized by disturbances of the reproductive system. The aim of the present study was: 1) to assess the hypothalamic pituitary -gonadal axis in patients with â-thal in relation to their phenotype and 2) to determine prognostic features of current gonadal status. We studied 135 patients (67 males and 68 females) with â-thal through history, physical examination, spermiograms and GnRH test. These patients were divided into â-thal major (51 males and 62 females) and â-thal intermedia phenotypes (16 males and 6 females). Male patients with â-thal major were subdivided into three groups a) eugonadal (35%, Tanners stage V, normal testicular volume, normal spermiograms, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanners stage II-V, low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin values and abnormal response to GnRH test) and c) patients with HH of early onset (41%, Tanners stage I, small testicular volume, abnormal spermiograms, abnormal basal and stimulated hormone values). Female patients with â-thal major were subdivided into: a) eugonadal (32%, Tanners stage V, regular menstruation, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (34%, Tanners stage II-V, secondary amenorrhea, subnormal basal and stimulated gonadotrophin values) and c) patients with HH of early onset (34%, Tanners stage I, primary amenorrhea, subnormal basal and stimulated hormone values). Patients with â-thal intermedia were subdivided into eugonadal (75% of males -33% of females) and hypogonadal (25% of males -67% of females). Current gonadal status could not be predicted by means of transfusion or chelation parameters. In conclusion, â-thal patients could be eugonadal or develop early or late onset HH. â-thal intermedia patients have a more favorable profile than â-thal major individuals. Current gonadal status of â-thal patients cannot be predicted by means of history, clinical or laboratory parameters

The Relevance of Blepharoptosis in Diagnostic Suspicion of Myopathies

Blepharoptosis (ptosis) is classified, based on etiology, into mechanical, cerebral, neurogenic, neuromuscular, myogenic, and due to miscellaneous causes. Primary myopathic diseases are rare causes of blepharoptosis and many patients with myogenic ptosis undergo a series of extensive investigations before a myopathy is being considered. In this study, we report four patients with different myopathic disorders who had blepharoptosis as a presenting symptom of their disease. Moreover, we highlight frequent diagnostic errors and difficulties in patients with myopathies who present blepharoptosis. Lack of clear cut aggravation of symptoms by fatigue and response to cholinesterase inhibitors treatment, the association of proximal, distal or extraocular muscle weakness, and positive family history or evidence of a multi systemic disorder should prompt evaluation of an underlying myopathy