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Brody Disease, an Early-Onset Myopathy With Delayed Relaxation and Abnormal Gait: A Case Series of 9 Children
Jamie I Verhoeven1, Jasper Kramer1, Juergen Seeger1
1From the Department of Neurology (J.I.V., J.K., J.P.M., B.G.V.E., N.C.V.), Donders Centre for Medical Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands; Sozialpädiatrisches Zentrum Frankfurt Mitte (J.S.), Neuromuskuläres Zentrum, Frankfurt, Germany; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Department of Pediatric Neurology (H.B., C.E.E.); Department of Genetics (E.-J.K.); Department of Laboratory Medicine (R.J.R.); Department of Pathology (B.K.), Radboud University Medical Centre, Amalia Children's Hospital, Nijmegen; and Department of Pediatric Neurology (S.K.), Erasmus University Medical Centre, Rotterdam, The Netherlands.
Insights
Brody disease, a rare genetic myopathy, causes delayed muscle relaxation after exercise. Early diagnosis in children is crucial for managing symptoms like difficulty running and abnormal gait.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Brody disease is a rare autosomal recessive myopathy linked to the ATP2A1 gene.
- It presents as exercise-induced delayed muscle relaxation, often misdiagnosed or diagnosed late.
- While historically diagnosed in adults, increasing use of genetic testing reveals childhood cases.
Purpose of the Study:
- To describe the clinical and genetic characteristics of Brody disease in children.
- To highlight the diagnostic challenges and delays in pediatric cases.
- To advocate for improved diagnostic pathways and genetic panel inclusion for Brody disease.
Main Methods:
- Clinical assessment of 9 children from 6 families with Brody disease.
- Review of medical histories, focusing on exercise-induced symptoms and gait abnormalities.
- Genetic analysis to identify pathogenic variants in the ATP2A1 gene.
Main Results:
- All 9 children exhibited exercise-induced delayed muscle relaxation, manifesting as difficulty running and performing sports.
- Muscle strength and mass were normal, with some children appearing athletic, but gait patterns were abnormal.
- Diagnostic delay ranged from 2 to 7 years, with various disorders considered before genetic testing confirmed Brody disease.
Conclusions:
- This case series emphasizes the importance of recognizing Brody disease in children presenting with exercise-induced muscle relaxation issues.
- Timely diagnosis can be improved by considering ATP2A1 gene variants in children with unexplained gait abnormalities and exercise intolerance.
- Recommendations include adding ATP2A1 to gene panels for congenital myopathies and movement disorders to facilitate earlier detection.
Abstract:
Brody disease is a rare autosomal recessive myopathy, caused by pathogenic variants in the ATP2A1 gene. It is characterized by an exercise-induced delay in muscle relaxation, often reported as muscle stiffness. Children may manifest with an abnormal gait and difficulty running. Delayed relaxation is commonly undetected, resulting in a long diagnostic delay. Almost all published cases so far were adults with childhood onset and adult diagnosis. With diagnostic next-generation sequencing, an increasing number of patients are diagnosed in childhood. We describe the clinical and genetic features of 9 children from 6 families with Brody disease. All presented with exercise-induced delayed relaxation, reported as difficulty running and performing sports. Muscle strength and mass was normal, and several children even had an athletic appearance. However, the walking and running patterns were abnormal. The diagnostic delay ranged between 2 and 7 years. Uniformly, a wide range of other disorders were considered before genetic testing was performed, revealing pathogenic genetic variants in ATP2A1. To conclude, this case series is expected to improve clinical recognition and timely diagnosis of Brody disease in children. We propose that ATP2A1 should be added to gene panels for congenital myopathies, developmental and movement disorders, and muscle channelopathies.
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