PMC9343628_01
Ultrasound images and histopathology of the prenatal and postnatal extremities. (A) Intrauterine ultrasound examination. (B,C) Postpartum high-frequency probe examination showed NM fetal upper limb muscle echo close to the humerus echo, and many hyperechoic regions (thin yellow arrows) in the muscle layer and subcutaneous tissue. (D) Right calf muscle Masson trichrome staining x 40 and (E) right calf muscle elastic fiber staining x 200. The muscle fiber fascicles were sparse and replaced by collagen fibers (thick red arrows) and elastic fibers (thick blue arrows). (F) Right calf skin H&E x 40 showed fibrous tissue (thick red arrows) proliferated in the dermis layer and subcutaneous tissue. (G-I) The normal fetal upper limb muscle echo was significantly lower than the humerus echo, and the subcutaneous tissue had low echo intensity with several echogenic septa of connective tissue. The thick white arrows point to the long bones of the fetal limbs. (J-L) The normal fetal right calf muscle H&E x 40, Masson trichrome staining x 40 and elastic fiber staining x40.
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F1
Interestingly, we found that echoes of the skeletal muscles were significantly enhanced (close to or slightly weaker than the bone echo) and had posterior echo attenuation (Figures 1A,B). Thr506Pro) (Supplementary Figure 1). Histopathological examination showed the following: (1) The muscle fibers were sparse, degenerated, and atrophied and were replaced by fatty-fibers (Figures 3C-F). (2) The dermis layer and subcutaneous tissue were thickened with fibrous tissue proliferation (Figure 1F); and (3) Nemaline bodies were positively stained with the anti-alpha-actinin antibody (Figures 3E,F).
Prenatal 3D ultrasound images and fetal echocardiography, postpartum gross anatomical specimens, X-ray photographs and cardiac anatomy. (A) Postmortem photo demonstrated multiple contractures of the upper and lower extremities. (B,C) Three-dimensional ultrasound showed fetal foot inversion and tilted fingers. (D) X-rays showed bilateral humerus and right femur fractures (thin white arrow). (E,F) Prenatal echocardiography showed a right ventricular double outlet with coarctation of the aortic arch. (G,H) Postpartum cardiac anatomy confirmed sonographic findings. In addition, there were four arteries of the aortic arch, from right to left: BA, the brachiocephalic artery; LCCA, the left common carotid artery; LVA, the left vertebral artery; and LSA, the left subclavian artery. RV, right ventricle; AO, aorta; PA, pulmonary artery; LPA, left pulmonary artery; RPA, right pulmonary artery; DA, ductus arteriosus; DAO, descending aorta; ARCH, aortic arch.
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F2
Serial scans were performed the following week, which confirmed limb stiffness (Figures 2B,C). Ultrasonographic findings led to the suspicion of AMC associated with amyoplasia, complex congenital heart disease (CHD) (Figures 2E,F), and polyhydramnios. Postmortem radiological examination, necropsy (Figures 2A,D), and pathology confirmed all sonographic findings and revealed other malformations. In addition, there were four arteries in the aortic arch (Figures 2G,H).
Anatomical and pathological images of the limb muscles. (A,B) Gross anatomy showed thickened subcutaneous fat (black star) and a thin muscle layer (black triangle) in the lower limbs of the fetus. (C) Right thigh muscle cross section H&E x 40 and (D) Right forearm muscle longitudinal section Masson trichrome x 40. The muscle bundles showed marked variation in size, and muscle fibers were replaced by fibrous tissue (thick black arrows) and adipose tissue (red star). (E,F) Right calf muscle cross section and longitudinal section anti-alpha-actinin antibody stained x 400. The muscle fibers were sparse, degenerated, and atrophied. Lots of nemaline rods in muscle fibers were strongly stained with anti-alpha-actinin antibody (thin black arrow).
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F3
The subcutaneous fat layer was significantly thickened, and the muscle layer was significantly thinner (Figures 3A,B). Histopathological examination showed the following: (1) The muscle fibers were sparse, degenerated, and atrophied and were replaced by fatty-fibers (Figures 3C-F). (2) The dermis layer and subcutaneous tissue were thickened with fibrous tissue proliferation (Figure 1F); and (3) Nemaline bodies were positively stained with the anti-alpha-actinin antibody (Figures 3E,F).