Dystrophinopathy

Clinical History

The patient is an 5-year-old male with progressive muscle weakness and elevated CPK. Gowers maneuver was noted on physical examination. Family history was negative for neuromuscular disorder. A muscle biopsy was performed.

What is the pathologic diagnosis based on images from frozen section H&E and Spectrin (image 1), DYS1 [similar appearance for DYS2 and DYS3] and utrophin (image 2)?

Answer: Dystrophinopathy

The muscle biopsy showed morphologic features of a chronic active non-inflammatory myopathy.  Note the significant increase in endomysial fibrous connective tissue (chronic process).

Staining for spectrin (tissue integrity control) is relatively intact, while there is complete loss of staining for DYS1 (also seen for DYS2 and DYS3 [not shown]), and increased expression of utrophin.

References/Additional Readings:

• Saad FA, Siciliano G, Angelini C. Advances in Dystrophinopathy Diagnosis and Therapy. Biomolecules. 2023 Aug 28;13(9):1319. doi: 10.3390/biom13091319. PMID: 37759719; PMCID: PMC10526396.
• Nix JS, Moore SA. What Every Neuropathologist Needs to Know: The Muscle Biopsy. J Neuropathol Exp Neurol. 2020 Jul 1;79(7):719-733. doi: 10.1093/jnen/nlaa046. Erratum in: J Neuropathol Exp Neurol. 2021 Mar 22;80(4):387. doi: 10.1093/jnen/nlaa096. PMID: 32529201; PMCID: PMC7304986.
• Falzarano MS, Scotton C, Passarelli C, Ferlini A. Duchenne Muscular Dystrophy: From Diagnosis to Therapy. Molecules. 2015 Oct 7;20(10):18168-84. doi: 10.3390/molecules201018168. PMID: 26457695; PMCID: PMC6332113.
• Chang RF, Mubarak SJ. Pathomechanics of Gowers’ sign: a video analysis of a spectrum of Gowers’ maneuvers. Clin Orthop Relat Res. 2012 Jul;470(7):1987-91. doi: 10.1007/s11999-011-2210-6. Epub 2011 Dec 28. PMID: 22203329; PMCID: PMC3369091.
• Pearce JM. Gowers’ sign. J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):149. doi: 10.1136/jnnp.68.2.149. PMID: 10644778; PMCID: PMC1736776.