PMC9884684_01
Pedigree of Case 1 (II-1) and Case 2 (III-1). Proband is indicated by the black arrow. Black and white shapes indicate clinically affected and unaffected individuals, respectively. Squares and circles indicate males and females, respectively.
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F1
During the workup of patient II-1, her then 18-year-old son (individual III-1, Figure 1) was incidentally found to have a systolic murmur and an abnormal ECG during a routine pre-operative assessment prior to elective nasal septoplasty.
Muscle biopsies from Case 1 (II-1; A-C) and Case 2 (III-1; D-F) showed features of myofibrillar myopathy. Hematoxylin & eosin staining (A, D) showed subtle subsarcolemmal (solid white arrows) and central basophilic hyaline inclusions (dotted white arrows). Variation in muscle fiber size is also noted in patient II-1 (A). Desmin immunohistochemistry (B, E) revealed subsarcolemmal (solid black arrows) and central (dotted black arrows) aggregates. Electron microscopy (C, F) showed subsarcolemmal osmiophilic granulofilamentous material (asterisk).
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F2
This showed findings consistent with a myofibrillar myopathy with frequent subsarcolemmal hyaline inclusions and occasional centrally-placed inclusions (Figure 2D) which stained positively on desmin immunohistochemistry (Figure 2E). Electron microscopy revealed the same osmiophilic granulofilamentous ultrastructure seen in his mother's biopsy (Figure 2F).
PMC9884684_02
Pedigree of Case 1 (II-1) and Case 2 (III-1). Proband is indicated by the black arrow. Black and white shapes indicate clinically affected and unaffected individuals, respectively. Squares and circles indicate males and females, respectively.
fneur-13-1110934-g0001.jpg
PMC9884684_02_fneur-13-1110934-g0001.jpg
F1
During the workup of patient II-1, her then 18-year-old son (individual III-1, Figure 1) was incidentally found to have a systolic murmur and an abnormal ECG during a routine pre-operative assessment prior to elective nasal septoplasty.
Muscle biopsies from Case 1 (II-1; A-C) and Case 2 (III-1; D-F) showed features of myofibrillar myopathy. Hematoxylin & eosin staining (A, D) showed subtle subsarcolemmal (solid white arrows) and central basophilic hyaline inclusions (dotted white arrows). Variation in muscle fiber size is also noted in patient II-1 (A). Desmin immunohistochemistry (B, E) revealed subsarcolemmal (solid black arrows) and central (dotted black arrows) aggregates. Electron microscopy (C, F) showed subsarcolemmal osmiophilic granulofilamentous material (asterisk).
fneur-13-1110934-g0002.jpg
PMC9884684_02_fneur-13-1110934-g0002.jpg
F2
This showed findings consistent with a myofibrillar myopathy with frequent subsarcolemmal hyaline inclusions and occasional centrally-placed inclusions (Figure 2D) which stained positively on desmin immunohistochemistry (Figure 2E). Electron microscopy revealed the same osmiophilic granulofilamentous ultrastructure seen in his mother's biopsy (Figure 2F).
Parasternal long axis (A, D), mid-diastolic apical four chamber (B, E) and end-systolic apical four chamber (C, F) transthoracic echocardiogram images from Case 2 at ages 18 (A-C) and 27 (D-F). At age 18, the ventricular (LV) wall was concentrically thickened (interventricular septum 20 mm, posterior LV wall 20 mm) with vigorous systolic function (LV ejection fraction was 60-65% by Simpson's biplane method). At age 27, the LV wall was thin (interventricular septum 10 mm, LV posterior wall 3 mm) and there was moderate-severe LV dysfunction (LV ejection fraction 35-40% by Simpson's biplane method).
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F3
T-wave inversions in anterolateral leads suggestive of left ventricular hypertrophy but there was no evidence of conduction system disease. TTE revealed concentrically increased left ventricular wall thickness (up to 20 mm) with preserved systolic function (ejection fraction 60-65% by Simpson's biplane method) and mild-moderate diastolic dysfunction (Figures 3A-C). Concurrently, sequential TTEs documented progressive reduction in left ventricular wall thickness (Figures 3D-F) and decline in left ventricular systolic function such that ejection fraction was 35-40% with global hypokinesis by age 27.
Cardiac magnetic resonance imaging of Case 2 (III-1) at age 18. (A) Axial T2 sequence showed increased left ventricular wall thickness (18.05 mm). (B) Short axis T2 fat saturation sequence showed increased signal in the mid ventricular wall (arrow). (C) Short axis T1 post-gadolinium sequence showed delayed gadolinium enhancement within the ventricular myocardium (arrow).
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F4
Cardiac magnetic resonance imaging (MRI) demonstrated increased left ventricular wall thickness predominantly affecting the anteroseptal and anterolateral walls (Figure 4A).
PMC9884684_03