Blue Rubber Bleb Nevus Syndrome with a Novel PDGFRA Variant and Comorbid Autism Spectrum Disorder: A Case Report

Background: Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder that primarily affects the skin and gastrointestinal tract, driven predominantly by somatic mosaic mutations, most commonly in TEK. Here, we report a case of a child with BRBNS and autism spectrum disorder (ASD). Case presentation: A 13-year-old boy diagnosed with ASD at 3 years presented with recurrent abdominal pain, blood in the stool, and severe anemia persisting for 6 months. At admission, his hemoglobin level was 5.6 g/dL. He had received a transfusion at age 6 for unexplained anemia. On examination, he appeared pale but stable, with bluish, compressible nodules on the right index finger and great toe, typical of BRBNS. Laboratory findings were consistent with chronic bleeding-induced iron deficiency. Endoscopic findings revealed multiple vascular lesions in the stomach, duodenum, ileum, and colon. Several colonic lesions were removed and pathologically confirmed as cavernous hemangiomas. Magnetic resonance enterography revealed additional small intestinal lesions. Whole-exome sequencing performed on buccal swab-derived DNA identified a heterozygous PDGFRA variant (c.2075G>T, p.Ser692Ile) classified as a variant of uncertain significance; no variants were identified in TEK, PIK3CA, or GNAQ. The patient underwent endoscopic resection of the larger lesions and received oral iron and a proton pump inhibitor. Hemoglobin stabilized at 11–12 g/dL, and no further transfusions were required. Conclusions: This case raises, but does not confirm, the possibility that genes other than TEK may contribute to BRBNS. The coexistence of ASD may be coincidental; a mechanistic link remains unproven. Careful endoscopic therapy and medical management controlled bleeding and anemia in this child.