SAT-741 - C Propeptide Cleavage Site Variant in COL1A2 (P.Asp1120Asn) Causing High BMD Osteogenesis Imperfecta

Objective
To present a practical triad imaging pattern, densitometric paradox, and genotype—that distinguishes high‑bone‑mineral‑density osteogenesis imperfecta (high BMD OI) from osteopetrosis and guides mandibular fixation.

Background
In high BMD OI, inefficient cleavage of the type I procollagen C terminal propeptide at the alanine aspartate (BMP1) site leaves residual propeptide, disrupts fibrillogenesis, and produces hypermineralized, low‑toughness bone dense on DXA yet fracture‑prone.

Case
We reported A 32 year old man with lifelong low trauma fractures and a residual left forearm deformity developed malocclusion and right mandibular pain after lower third‑molar extraction. CT showed a right mandibular angle fracture. Primary low‑profile miniplate fixation failed with recurrent displacement and malunion. Two sons had childhood fractures, suggesting autosomal‑dominant inheritance.

Investigations
Biochemistry was unremarkable (calcium, phosphate, parathyroid hormone, alkaline phosphatase, renal function); 25‑hydroxyvitamin D was sufficient. Skeletal survey showed generalized osteosclerosis with calvarial thickening ; no bone within bone or rugger jersey signs . DXA Z‑scores were paradoxically high: lumbar spine +4.2, left femoral neck +4.8, right femoral neck +1.9.

Genetic Findings
Clinical NGS identified heterozygous COL1A2 c.3358G>A (p.Asp1120Asn) at the C pro-peptide cleavage site ; classified likely pathogenic (ACMG/AMP) in context of phenotype and inheritance .

Management/Outcome:
The mandible was treated as pathologic bone: rigid, load bearing locking reconstruction with long bicortical screws and precise occlusal control, rather than repeating mini-plates. Our Endocrine care emphasized vitamin D ، calcium sufficiency, fracture risk counseling, dental precautions , and cascade genetic testing; antiresorptives were deferred until complete mucosal and radiographic union to limit MRONJ risk.

Conclusion
High BMD ≠ strong bone . The triad axial predominant sclerosis without osteopetrotic stigmata, the densitometric paradox and a COL1A1/2 C pro-peptide cleavage site variant diagnoses high BMD OI and redirects mandibular fracture care toward rigid load bearing fixation with genotype guided family management.

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