Genetically Confirmed Osteogenesis Imperfecta (COL1A1) With Unexplained Ambiguous Genitalia in a 46,XY Child: An Index Case Report

Osteogenesis imperfecta (OI) is a heritable disorder of type I collagen characterized by bone fragility, blue sclerae, and short stature. Disorders of sex development (DSD) in 46,XY individuals demand comprehensive endocrine, imaging, and genetic evaluation. We report a 6-year-old child with recurrent low-impact fractures, blue sclerae, short stature, and ambiguous genitalia. Karyotype was repeatedly reported as 46,XY. Subsequent endocrine evaluation revealed elevated follicle-stimulating hormone (16.03 mIU/mL), low luteinizing hormone (1.35 mIU/mL), markedly reduced testosterone (< 7 ng/dL), low dehydroepiandrosterone sulfate (< 15 μg/dL), and androstenedione (< 0.300 ng/mL), consistent with primary gonadal dysgenesis. Congenital adrenal hyperplasia was provisionally excluded. Whole-exome sequencing identified a heterozygous pathogenic frameshift variant in COL1A1 (c.441delC; p.Gly148fs*117), confirming OI, and a heterozygous CYP11A1 variant of uncertain significance (c.119 T > C; p.Ile40Thr), possibly contributing to partial adrenal insufficiency and sex reversal. The patient receives annual zoledronate, calcium, and vitamin D supplementation, with ongoing multidisciplinary follow-up. This represents the first reported coexistence of OI due to COL1A1 mutation with ambiguous genitalia in a 46,XY child, emphasizing the complexity of overlapping skeletal and gonadal phenotypes and the importance of longitudinal care.