Neurogenetics: Congenital Myotonic Dystrophy with asymptomatic mother may be missed by whole exome sequencing; Biopsy, DMPK1 gene testing and EMG may be required to resolve VUS in neonates, A Case report. (P6-8.010)

Abstract

<h3>Objective:</h3> We show how biopsy, EMG, and <i>DMPK1</i> gene testing may be required for variant resolution. Whole exome sequencing revealed <i>NEB</i> (nebulin) (OMIM #161650) variants of uncertain significance inherited in <i>trans</i>. Muscle biopsy and EMG were helpful in resolving <i>NEB</i> VUS (variants of uncertain significance) and the detection of myotonia even as young as 6 days of age, with a clinically asymptomatic mother. <h3>Background:</h3> Myotonic dystrophy type 1 (myotonia dystrophia 1) is an autosomal dominant multisystem disorder caused by CTG expansion of the <i>DMPK1</i> gene (dystrophia myotonica protein kinase) (OMIM #605377) resulting in anticipation, whereby offspring have greater repeat expansion and severity. <h3>Design/Methods:</h3> <h3>Case Report:</h3> This full-term patient was born with severe hypotonia and respiratory depression. Brain MRI, EEG, Karyotype (46, XY) and FISH were normal. Whole Exome Sequencing (WES) revealed heterozygous <i>NEB</i> VUS, in <i>trans</i>, but histochemical and electron microscopic examinations of the muscle biopsy did not show nemaline rods. EMG was performed and revealed myotonic discharges. A genetic diagnosis of myotonic dystrophy type 1 was made, with over 200 CTG repeats in the <i>DMPK1</i> gene. A week after tracheostomy and g-tube placement, oxcarbazepine was trialed, after which he was able to be weaned off ventilation and discharged to home. He made substantial progress over the next year. <h3>Results:</h3> NA <h3>Conclusions:</h3> Neonatal muscle biopsies may not show nemaline rods due to being early or sampling error and thus further testing may be required. When evaluating severe congenital myopathies, testing for myotonic dystrophy should be considered. Myotonia may be found in neonates as young as 6 days old characterized as briefer duration with waning repetitive small amplitudes between 50–100uV without the classic sound on a spectrum with complex repetitive discharges. Severe congenital myotonic dystrophy patients may be born from an asymptomatic mother and the diagnosis may be missed by whole exome sequencing. <b>Disclosure:</b> Mr. Appiah has nothing to disclose. Dr. Shergelashvili has nothing to disclose. Dr. Marr has nothing to disclose. Ahmed Eldokla has nothing to disclose. Dr. LEBEL has nothing to disclose. Dr. Sakonju has nothing to disclose.