SUN-712 Osteogenesis Imperfecta Type VII: A Rare Case Report

Abstract Disclosure: R.C. Williams: None. S.S. Dahir: None. C.R. Lichtenfeld: None. L.T. Drake: None. L.R. Rehm: None. K.M. Dahir: Alexion Pharmaceuticals, Inc., Ultragenyx, Kyowa Kirin. Background: Osteogenesis Imperfecta (OI) is a group of rare inherited connective tissue disorders with low bone mass and fragility. In most cases, there is a reduction in the production or synthesis of normal type I collagen most commonly due to mutations in the COL1A1/COL1A2 genes. OI type VII is an autosomal recessive form of severe or lethal OI characterized by fractures at birth, bluish sclerae, early deformity of lower extremities, coxa vara, and osteopenia. Clinical manifestations of OI type VII include recurrent fractures that decrease after puberty and increased bone turnover. Affected individuals commonly exhibit below-average height and shortened upper arm and thigh bones. OI Type VII is caused by a homozygous or compound heterozygous mutation in the CRTAP gene on chromosome 3p22. Case Description: A 24-year-old Hispanic male presented for consultation of transition of care from pediatrics for a diagnosis of OI established at 8 days of age. The patient had no family history of the condition. Genetic screening for COL1A1 and COL1A2 gene mutations revealed no OI-associated abnormalities. At birth, he had bilateral femur fractures in both legs and broke his humerus and femur at ages 1 and 5 months, respectively. In his first 8 years of life, he had repeated breaks to both femurs as well as a left humerus and vertebral fracture. All fractures have been without trauma, such as reaching for an object. His last fracture was at age 14 which resulted in intermedullary rod placed. Prior medical management was IV Pamidronate initiated at the age of 7 and continued until the age of 16. Evaluation at age 24 was remarkable for marked joint laxity, opalescent dentin with brownish discoloration of malformed teeth, short stature with shortened upper arms, normal hearing and DXA scan normal. Genetic testing results revealed homozygous likely pathogenic variants in CRTAP c.471+4A>G and a variant of uncertain significance in the ANO5 c.1606A>C9. Conclusions: The diagnosis of osteogenesis imperfecta (OI) type VII was confirmed through a combination of genetic testing for CRTAP mutations and clinical history. While most OI cases (approximately 90%) result from COL1A1/COL1A2 mutations, distinguishing OI type VII relies on identifying pathogenic variants in CRTAP, a gene critical for collagen type I biosynthesis. A homozygous CRTAP mutation leads to OI due to a deficiency in cartilage-associated protein (CRTAP), impairing collagen modification. Expanded genetic testing panels play a crucial role in facilitating earlier diagnosis and intervention, particularly for individuals presenting with OI-consistent features but lacking COL1A1 and COL1A2 mutations. Incorporating CRTAP and other rare OI-related genes into routine diagnostic workflows enhances the detection of atypical OI subtypes, allowing for timely management and tailored treatment strategies that can improve patient outcomes. Presentation: Sunday, July 13, 2025