PMC9593155_01
A pedigree chart of the present case. Pin dots indicate affected members carrying the Cys302Gly/Arg303Trp mutations and black symbols indicate affected members carrying an exon 6 large deletion. Question marks indicate members with unknown genotype. "I," "II," "III," and "IV" indicate the generation of this family. Squares indicate men, circles indicate women. Asterisks indicate members clinically diagnosed with hypercholesterolemia.
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Moreover, she had a family history of hyperlipidemia as well as sudden cardiac death on the paternal and maternal sides of her family (Fig. 1, Table 1). Although the leaflets of her aortic valve were almost intact with preserved mobility (Fig. 3A, B, Supplementary material 1), severe left ventricular outflow tract stenosis was detected, with a peak gradient of 87 mmHg on transthoracic echocardiography (Fig. 3C).
Xanthelasma palpebrarum (A), xanthoma tendinosum on the finger's extensor muscle (B), Achilles' tendons (C), and radiograph of the left Achilles' tendon (D).
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Achilles' tendons (Fig. 2). An ejection systolic grade IV/VI murmur was heard on the right second intercostal space radiating toward the jugular.
The transesophageal echocardiogram shows that the leaflets of the patient's aortic valve had preserved mobility in the parasternal long axis view (A; end systolic) and in the parasternal short axis view (B; end systolic). Severe left ventricular outflow tract stenosis with a peak gradient of 87 mmHg is revealed by transthoracic echocardiography using continuous wave Doppler (C). Transesophageal echocardiography shows left ventricular outflow tract stenosis in the parasternal long axis view (D; end diastolic, AA=19 mm, STJ=23 mm, Ao=27 mm). LA: left atrium, LV: left ventricle, Ao: aorta, RA: right atrium, AA: aortic annulus, STJ: sinotubular junction
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Although the leaflets of her aortic valve were almost intact with preserved mobility (Fig. 3A, B, Supplementary material 1), severe left ventricular outflow tract stenosis was detected, with a peak gradient of 87 mmHg on transthoracic echocardiography (Fig. 3C). The patient had mild concentric left ventricular hypertrophy (10 mm) and a narrow annulus followed by SVAS (Fig. 3D).
Computed tomographic findings of the patient's aortic valve and ascending aorta. Arrowheads indicate the site of supravalvular aortic stenosis. AV: aortic valve, LV: left ventricle, RA: right atrium, RV: right ventricle
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Cardiac computed tomography demonstrated severe calcification and a hypoplastic sinus of Valsalva due to SVAS (Fig. 4).
Coronary angiography and aortography. Coronary angiography of the right coronary artery (A) and left coronary artery (B) demonstrates slight irregularity of both the left main trunk and right coronary ostium. Aortography of the aortic root shows supravalvular aortic stenosis with severe calcification (C; LAO: left anterior oblique, D; RAO: right anterior oblique). Arrowheads indicate the site of supravalvular aortic stenosis. LCA: left coronary artery, RCA: right coronary artery
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Although coronary angiography showed slight irregularity of both the left main trunk and right coronary ostium, there was no significant stenotic lesion in her coronary arteries (Fig. 5A, B). Cardiac catheterization examination revealed SVAS with severe calcification and a pressure gradient of 75 mmHg between the left ventricle and aortic root (Fig. 5C, D).
The clinical course of the patient. LDL: low-density lipoprotein
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LDL-C level from 429 to 253 mg/dL (Fig. 6). LDL apheresis therapy (once every 4 weeks) was also introduced because of the insufficient reduction of LDL-C.