BAG3 myofibrillar myopathy presenting with cardiomyopathy.
Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy.
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: ckonersman@ucsd.edu.
Chamindra G
CG
Konersman
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Brett J
BJ
Bordini
Department of Pediatrics, Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Gunter
G
Scharer
Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Michael W
MW
Lawlor
Department of Cardiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Steven
S
Zangwill
Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
James F
JF
Southern
Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Louella
L
Amos
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Gabrielle C
GC
Geddes
Department of Pediatrics, Undiagnosed and Rare Disease Program, Medical College of Wisconsin, Milwaukee, WI, USA.
Robert
R
Kliegman
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Michael P
MP
Collins
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D009202:Cardiomyopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D020125:Mutation, Missense; D020914:Myopathies, Structural, Congenital / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D009431:Neural Conduction; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human
BAG3; Bcl-2-associated athanogene 3; Myofibrillar myopathy; Neuropathy; Restrictive cardiomyopathy