"and DPM3    while showing reduced alpha-dystroglycan and elevated CK, also present with cognitive impairment, microcephaly, cerebellar hypoplasia, feeding difficulties and notably severe myoclonic epilepsy. Recessive mutations in DOLK so far present mostly as a dilated cardiomyopathy . "
[Show abstract][Hide abstract] ABSTRACT: Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical as well genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis.
"Cardiac abnormalities have already been reported in CMD patients with dystroglycanopathies [15–18], mainly associated with FKRP and fukutin mutations. In particular, dilated cardiomyopathy has been found to occur frequently in patients with FKRP mutations and LGMD2I phenotype [19–22] but has also been reported in five cases of patients with CMD phenotype [15,23–25]. In our cohort including only CMD patients, cardiac involvement was found in 3 of the 13 patients with FKRP mutations, two of whom had already been reported . "
[Show abstract][Hide abstract] ABSTRACT: The aim of this retrospective study was to assess respiratory and cardiac function in a large cohort of patients with congenital muscular dystrophies (CMD) with reduced glycosylation of alphadystroglycan (α-DG). Thirteen of the 115 patients included in the study died between the age of 1 month and 20 years. The age at last follow up of the surviving 102 ranged between 1 year and 68 years (median: 9.3 years). Cardiac involvement was found in 7 of the 115 (6%), 5 with dilated cardiomyopathy, 1 cardiac conductions defects and 1 mitral regurgitation. Respiratory function was impaired in 14 (12%). Ten of the 14 required non invasive nocturnal respiratory support, while the other four required invasive ventilation. Cardiac or respiratory involvement was found in patients with mutations in FKRP, POMT1, POMT2. All of the patients in whom mutation in POMGnT1 were identified had normal cardiac and respiratory function.
"Within this group, some patients present with evidence of both aDGpathy and a congenital disorder of glycosylation and in whom mutations in the dolichol phosphate mannose 1, 2 and 3 genes are now being recognized.53 These patients may present with cognitive impairment, microcephaly, cerebellar hypoplasia, feeding difficulties and severe myoclonus epilepsy.54 Further broadening of the genetic and phenotypic spectrum of the aDGpathies is to be expected. "
[Show abstract][Hide abstract] ABSTRACT: Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous neuromuscular disorders with onset at birth or in infancy in which the muscle biopsy is compatible with a dystrophic myopathy. In the past 10 years, knowledge of neuromuscular disorders has dramatically increased, particularly with the exponential boost of disclosing the genetic background of CMDs. This review will highlight the clinical description of the most important forms of CMD, paying particular attention to the main keys for diagnostic approach. The diagnosis of CMDs requires the concurrence of expertise in multiple specialties (neurology, morphology, genetics, neuroradiology) available in a few centers worldwide that have achieved sufficient experience with the different CMD subtypes. Currently, molecular diagnosis is of paramount importance not only for phenotype-genotype correlations, genetic and prenatal counseling, and prognosis and aspects of management, but also concerning the imminent availability of clinical trials and treatments.
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