Autosomal Recessive Osteogenesis Imperfecta
Michael T. Steuerwald, MD; Constance Gong, MD; Selena L. Hariharan, MD; and Jennifer L. Reed, MD
Cincinnati Children’s Hospital Medical Center,
Cincinnati, Ohio
A 5-week-old girl with an uncomplicated birth history presented to a pediatric emergency department with concern for swelling of her right leg. There had been no known traumatic event.
On physical examination, the well-appearing infant held her leg flexed and externally rotated. Swelling of the right thigh was noted, and plain radiography confirmed a right midshaft femur fracture that was concerning for nonaccidental trauma. Further evaluation including a radiographic skeletal survey demonstrated numerous other fractures, including an unstable C2 vertebral fracture, multiple rib fractures in various stages of healing, and possible wormian bones in the calvaria (A).
Laboratory test results were notable for an elevated alkaline phosphatase level, an elevated platelet count, and a low vitamin D level. A computed tomography scan of the head confirmed numerous wormian bones without any intracranial hemorrhage (B).
The infant was admitted to the hospital for further evaluation and management of her fractures. During her hospitalization, specialists in orthopedics, genetics, and endocrinology were consulted and concluded that the clinical findings were concerning for a bone fragility syndrome such as osteogenesis imperfecta (OI), considering the inconsistent injury pattern and the presence of wormian bones. These bones are the product of abnormal ossification centers within the cranium, and their initial formation it is thought to be secondary to increased dural strain within the cranial sutures.1
Type I collagen gene sequencing was completed, but no gene mutations were identified in COL1A1 or COL1A2. Testing for rare autosomal recessive variants of OI was performed, and a mutation in FKBP10 was identified. This gene encodes for a protein chaperone whose function is essential to proper collagen formation; some authors refer to this mutation as type XI OI.2
Vitamin D insufficiency may be observed in up to 50% of patients with OI and could exacerbate primary bone disease if the insufficiency is not treated properly.3 High-dose vitamin D replacement therapy was initiated, and normal blood levels were achieved in the infant shortly thereafter.
At a follow-up visit at 16 months of age, the girl had no additional fractures, and she exhibited good remodeling of prior fractures on radiography. She is on daily oral vitamin D supplementation, undergoes physical therapy for balance and coordination, and is able to sit without assistance.
In children younger than 2 years of age, specific fracture patterns such as long-bone fractures, posterior rib fractures, metaphyseal corner fractures, and fractures in various stages of healing are highly suggestive of nonaccidental trauma.4 Because this infant did not have a family history of metabolic bone disease, early deaths, hearing loss, or fractures, suspicion was high for inflicted orthopedic injury.
After further evaluation, however, the profound number of wormian bones on plain radiography and head computed tomography, in conjunction with the sheer number of fractures on skeletal survey, led to the consideration of other diagnoses, including metabolic bone disease.
This infant’s case demonstrates the importance of developing a broad differential diagnosis that includes all organic causes of orthopedic trauma in addition to nonaccidental injuries.
References
1. Bellary SS, Steinberg A, Mirzayan N, et al. Wormian bones: a review. Clin Anat. 2013;26(8):922-927.
2. Rohrbach M, Giunta C. Recessive osteogenesis imperfecta: clinical, radiological, and molecular findings. Am J Med Genet C Semin Med Genet. 2012;160C(3):175-189.
3. Wilsford LD, Sullivan E, Mazur LJ. Risk factors for vitamin D deficiency in children with osteogenesis imperfecta. J Pediatr Orthop. 2013;33(5):575-579.
4. Jenny C, Hymel KP, Ritzen A, Reinert SE, Hay TC. Analysis of missed cases of abusive head trauma. JAMA. 1999;281(7):621-626.