PRKAG2 Syndrome: Clinical Features, Imaging Findings and Cardiac Events

Figures

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  Figure 1. Pedigrees of families with PRKAG2 variants. Legend: squares denote males, circles for females; numbers denote age at death in years, black color—affected, grey color—borderline/uncertain phenotype; subjects tested genetically are marked either by the name of the heterozygous PRKAG2 variant or as “WT”, if negative for PRKAG2 variant detected in the proband.

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  Figure 2. 12-lead standard electrocardiogram in 7 patients with PRKAG2 variants. Patient 1: Sinus rhythm 68 bpm, normal QRS axis of −27°, PR 194ms, QRS 150 ms, RBBB, left ventricular and right ventricular hypertrophy, biatrial enlargement, ST depression and T-wave inversions in I, aVL and V1-6 secondary to RBBB and biventricular hypertrophy. Patient 2: Sinus rhythm 62 bpm, normal QRS axis of 68°, short PR interval of 120 ms, notched QRS of 110 ms in III, aVF, V1, narrow q waves in leads V5–V6. Right ventricular hypertrophy, ST depression in II, III, aVF. Patient 3: Sinus rhythm 64 bpm, normal QRS axis of −3°, short PR interval of 113 ms, QRS 128 ms, preexcitation pattern. Patient 4: Sinus bradycardia 43 bpm, normal QRS axis of −8°, PR 127 ms, QRS 146 ms, interventricular conduction delay (LBBB-like pattern), LVH and profound repolarization abnormalities (negative deep T waves in II, III, aVF and V1–V4). Patient 5: Sinus bradycardia 46 bpm, left axis deviation of −45°, PR 150 ms, QRS 130 ms, RBBB, LAFB, left atrial enlargement, LVH, RVH. Patient 6: Sinus rhythm 60 bpm, left axis deviation of −46°, PR 140 ms, QRS 135 ms. rSR’ in V1. LVH with intraventricular conduction delay and secondary…

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  Figure 3. Endomyocardial bioptate images. (A) Hypertrophied cardiomyocytes with enlarged pleomorphic nuclei, HE ×200. (B) Periodic acid–Schiff–positive deposits corresponding to glycogen in cardiomyocytes (arrows), PAS ×200.

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  Figure 4. Cardiac magnetic resonance images. Patient 2: An examination performed at the age of 71 revealed increased interventricular septum thickness (16 mm), normal left ventricular (LV) function (LV ejection fraction (LVEF 75%) and enlarged left atrium. LV mass was increased (68 g/m2). No late gadolinium enhancement (LGE) was seen. Patient 3: A CMR study performed at the age of 31 revealed asymmetric LV hypertrophy with a maximum muscle thickness of up to 19 mm at the border of the middle segment of the inferior wall and the middle infero-septal segment. Slight enlargement of the left atrium. LVEF of 61%. The images following gadolinium-based contrast agent administration revealed small, patchy foci of LGE. Patient 4: A CMR examination performed at the age of 45 revealed the borderline for the diagnosis of cardiomyopathy thickness of the interventricular septum (12–13 mm). Good LV function (LVEF 69%) was observed. No LGE was detected. Patient 5: A CMR performed at age of 43 revealed LV wall thickness of maximum 12–13 mm within the interventricular septum and a slight enlargement of the LV cavity. Normal LV function (LVEF 77%) was preserved. No LGE was present.

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  Figure 5. Coronary computed tomography angiography. Image of left anterior descending artery (LAD) in systole (A) and diastole (B). On the left side of the respective images coronary artery cross sections illustrating the depth of the intramuscular course of the mid arterial segment. Notably, the mid LAD within the myocardial muscle displays signs of compression with dynamic stenosis during the systolic phase.