Abstract Details

Title Inherited Myopathy Plus: Double-Trouble from Rare Neuromuscular Disorders

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 11-010

Objective To underscore the critical role of clinical assessment and integration of molecular findings with patient's phenotype, by describing a series of patients affected by inherited myopathy and coexistent independent “rare” neuromuscular diseases (NMD).

Background In USA, a “rare” disorder is one that affects <200,000 people, making inherited myopathies “rare” diseases. Increasing access to genetic testing has been instrumental for the diagnosis of inherited myopathies. Genetic findings require clinical correlation due to multiple factors, including variable phenotype, polygenic etiology of certain inherited disorders, and possible co-existing independent NMD.

Design/Methods We searched the Rochester Mayo Clinic medical record (2004-2020) to identify adult patients with a genetically characterized myopathy and coexisting independent NMD recognized as “rare” at https://rarediseases.info.nih.gov/. Clinical and laboratory findings were reviewed.

Results We identified 9 patients from 8 families fulfilling search criteria. Four patients had a “double-trouble” inherited myopathy: distal myopathy and cardiomyopathy due to TIA1 and MYH7 heterozygous mutation (2 patients); limb-girdle muscular dystrophy (LGMD) due to FKRP homozygous and LMNA heterozygous mutations (1 patient); and LGMD due to FKRP homozygous mutation coexisting with 4 RYR1 variants (three variants in cis and a fourth variant in trans, previously reported in central-core disease) (1 patient). One patient with mitochondrial myopathy due to a 6.5 kb mtDNA deletion and 1 patient with caveolinopathy-3 had coexistent idiopathic inflammatory myopathy, featuring inclusion body myositis in the caveolinopathy-3. Three patients had myotonic dystrophy type 2, coexisting with ALS (2 patients) or Parsonage-Turner-like (1 patient). In addition to the 9 aforementioned patients, we identified a female patient with distal spinal muscular atrophy carrying a DMD mutation and a Sandhoff disease patient with a cardiomyopathy-associated MYH7 mutation.

Conclusions These cases highlight the importance of correlating genetic and clinical findings for definite diagnosis, optimal care, and prognosis. They may also suggest a need for refining the epidemiological estimate of “rare” disease.

Authors/Disclosures
Andre Granger, MD, MBA (Mayo Clinic) PRESENTER	Dr. Granger has nothing to disclose.
Grayson B. Beecher, MD (University of Alberta)	Dr. Beecher has nothing to disclose.
Teerin Liewluck, MD, FAAN (Department of Neurology, Mayo Clinic)	Dr. Liewluck has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. Liewluck has received publishing royalties from a publication relating to health care.
Ruple S. Laughlin, MD, FAAN (Mayo Clinic Rochester)	Dr. Laughlin has nothing to disclose.
Margherita Milone, MD, FAAN (Mayo Clinic)	Dr. Milone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cartesian Therapeutics. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, AAN. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.

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