PMC6949664_01
Ocular phenotype (case 1). Multiple lesions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) shown inferiorly and pigmentation near the optic nerve in the right eye of a female with aphakia after surgical removal of congenital cataracts.
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Bilateral early secondary glaucoma/ocular hypertension, bilateral inferior multifocal congenital hypertrophy of the retinal pigment epithelium (CHRPE) with pigmentation adjacent to the optic disc in the right eye (Figure 1), and a scalp hemangioma (Figure 2) were noted.
Involuted frontal scalp hemangioma (case 1).
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Bilateral early secondary glaucoma/ocular hypertension, bilateral inferior multifocal congenital hypertrophy of the retinal pigment epithelium (CHRPE) with pigmentation adjacent to the optic disc in the right eye (Figure 1), and a scalp hemangioma (Figure 2) were noted.
Dental phenotype (case 1).
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At that time, the patient's re-evaluated developmental history was significant for a history of VSD, dental anomalies (persistent baby teeth, fused baby teeth, delayed eruption of secondary teeth, and long roots) (Figure 3), flat feet, a high-arched palate, and facial features that do not resemble other family members.
PMC6949664_02
Ocular phenotype (case 2). Multiple lesions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) present bilaterally ((a) right eye; (b) left eye) in a female with aphakia after surgical removal of congenital cataracts. Asymmetric increased cup to disc ratio was present in the left eye.
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Examination under anesthesia revealed a hemangioma near her right eyebrow and a soft protuberance at her posterior scalp, IOPs in both eyes controlled on topical glaucoma medications required only in the right eye, bilateral multiple CHRPE (Figure 4), and axial eye lengths indicating left eye microphthalmia.
MRI/MRA images (case 2). (a) Sagittal MRI (T1) image of the brain showing a 1.2 cm diameter extracranial hemangioma on the right frontal scalp (red arrow). (b) Coronal MRI (postcontrast T1W) image showing the larger hemangioma on the right parietal scalp. (c) Axial MRI image (postcontrast T1W) showing both the smaller hemangioma on the right frontal scalp and the larger hemangioma on the right parietal scalp measured 2.9 x 2.3 cm axially. (d) Axial MRI image (SWI) showing both the smaller hemangioma on the right frontal scalp and the larger hemangioma on the right parietal scalp. (e) Head and neck MRA showing intracranial circulation and the large right parietal scalp hemangioma (red arrow). (f) Head MRA showing intracranial circulation and direct circulation (red arrow) to the right parietal scalp hemangioma. (g) Upper body MRA showing branching of upper body large arteries. (h) Zoomed in and angled upper body MRA showing the aberrant right subclavian artery (red arrow) coming directly off the aortic arch and not from the brachiocephalic artery (as it normally should). There is no observed right brachiocephalic artery.
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Due to this finding, she underwent brain MRI/MRA at 12 months of age which showed a large enhancing lesion of the right parietal scalp measuring up to 3.9 x 2.3 cm axially, interpreted as a likely hemangioma (Figure 5).
Dental phenotype (case 2).
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Her parents also reported that she had long roots of her teeth with one missing tooth and first primary tooth loss at 6-7 years of age (Figure 6).
Gene set enrichment analysis. BCOR (red label, horizontal) was found to overlap with other genes in the pathway for "circulatory system development" (red label, vertical).
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When BCOR is added among BRAF, GNA11, GNAQ, KRAS, MAP2K1, MTOR, NRAS, PIK3CA, PIK3R1, and RASA1, GSEA shows that BCOR overlaps significantly with other genes in the pathway of domain of "circulatory system development (Figure 7)."