3. Neurogenetic Disorders – (DMD, SMA, CMT, NF1) Ondemand-M03 Neurogenetic Disorders ELyon Notes

M03 Neurogenetic Disorders ELyon Notes

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This document discusses various genetic disorders including muscular dystrophy (DMD, Becker type), spinal muscular atrophy (SMA), Charcot Marie Tooth (CMT), and neurofibromatosis (NF1). It provides information on the methodology used for testing each disorder, test performance evaluation, interpretation of test results, and testing limitations. <br /><br />Muscular dystrophy is characterized by muscle weakness, pseudohypertrophy of the calves, and impaired heart and respiratory muscles. It is inherited in an X-linked recessive manner, with DMD affecting males and rarely surviving beyond 30, while BMD has a slower course and milder symptoms. Dystrophin gene mutations are responsible for these types, with large deletions causing DMD and in-frame deletions causing BMD.<br /><br />Spinal muscular atrophy is a lower motor neuron disease characterized by symmetrical limb and trunk weakness, muscular atrophy, and degeneration of spinal cord cells. It is inherited in an autosomal recessive manner and is a common cause of death in infancy. Molecular testing is available to confirm SMN1 deletion and the presence of at least one copy of SMN2.<br /><br />Charcot Marie Tooth is a group of disorders characterized by distal limb muscle weakness and atrophy. It is inherited in various patterns, including autosomal dominant. PMP22 duplication is the most common cause of CMT1, while other genes are associated with different CMT types and subtypes.<br /><br />Neurofibromatosis is characterized by the presence of cafe-au-lait macules, freckling, neurofibromas, and other features. It is inherited in an autosomal dominant manner, although de novo mutations are common. Molecular testing for NF1 involves detecting pathogenic variants in the NF1 gene, including deletions/duplications.<br /><br />The document also discusses the use of molecular testing for diagnosis, prognosis, and risk assessment in these disorders. Testing methods include molecular techniques such as PCR, MLPA, and sequencing. The importance of ethnic-specific residual risk and the availability of newborn screening for SMA are also mentioned.

Keywords

genetic disorders

muscular dystrophy

spinal muscular atrophy

Charcot Marie Tooth

neurofibromatosis

testing methodology

molecular testing

autosomal recessive

autosomal dominant

newborn screening