case_images: PMC10534027_01
case_images: (A) Central echogenicity of the lens (arrow) indicating congenital cataract at 23 WG; (B) normal lateral ventricle (arrow) at 23 WG; (C) ventriculomegaly of 13.4 mm at 34 WG indicating the progressive nature of the disease; (D) T2 FSE axial brain. Large ventricles: Right frontal porencephalic cysts bold arrows: hemorrhagic cystic malacia. Interhemispheric cyst connecting the lateral ventricles thin arrow; (E) sagittal brain T2 fast spin echo (mri sequence name) (FSE) thin arrow: closed aqueduct; (F) swan axial brain thin arrow: hemorrhagic cavity; blood product in the lateral ventricles; (G) brain CT scan without contrast media: after VP shunt. Bilateral, extensive, cortical calcifications (white arrows); (H) a spot of basal nuclei calcification on the left (white arrow); (I) MRI after VP shunt. Mid sagittal. The corpus callosum is not seen; (J) MRI after VP shunt. Shunt in the right side (RT) lateral ventricle (thin arrow). The third and lateral ventricles are very small, and the subarachnoid spaces are enlarged (thick arrow), due to decrease of the pressure; (K) the cystic malacia changes decreased in size (thin arrow); (L) intracranial blood products are more clumped (curved arrow).
case_images: fped-11-1178280-g001.jpg
case_images: PMC10534027_01_fped-11-1178280-g001.jpg
case_images: F1
case_images: The sonography at 23 WG demonstrated bilateral centric cataracts and echogenicity in the lateral brain ventricles (Figures 1A,B). The brain fetal sonography at 30 WG showed dilated lateral ventricles up to 13 mm, irregularity of ventricle walls, and suspected underdeveloped sulci (Figure 1C). A large infra-tentorial fluid collection was depicted (Figures 1D-F). Extensive brain calcifications were observed, mainly cortical and subcortical and less calcification in the basal ganglia (Figures 1G,H). The brain MRI at age 5 months showed the absence of the CC (Figure 1I) and the Probst bundles, suggesting that the CC was destroyed. Blood products in lateral ventricles and in the third ventricles and parenchymatic hemorrhage in the left parietal and temporal hemispheres were more clustered (Figures 1J-L). Blast (https://blast.ncbi.nlm.nih.gov/Blast.cgi) by alignment to GRCh38 assembly, revealing a novel pathogenic frameshift homozygous variant: c.745dup, p. (Val249Glyfs*28), according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Both parents were heterozygous (Supplementary Figure S1).
case_images: Our patient at 7 months of age (A) and 30 months (B) with evolving dysmorphic features which are now more prominent. Photophobia, high forehead with low anterior hair line, thin nasal bridge, synophrys with high arched eyebrows, epicanthus with down slanting eyes, micro retrognathia, posteriorly rotated ears, puffed cheeks, and short neck with abundant skin folds.
case_images: fped-11-1178280-g002.jpg
case_images: PMC10534027_01_fped-11-1178280-g002.jpg
case_images: F2