What is the most likely molecular defect responsible for the clinical and radiographic findings of bowleg deformity, metaphyseal flaring, and inverted V-shape distal femoral physis in a 3-year-old boy with a history of hypotonia (low muscle tone) and short stature?

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Differential Diagnosis

  • Single most likely diagnosis:
    • B) Fibroblast growth factor 3: The clinical presentation of bowleg deformity, metaphyseal flaring, inverted V-shape distal femoral physis, and a disproportionately long fibula is highly suggestive of Achondroplasia, the most common form of short-limbed dwarfism. Achondroplasia is caused by a defect in the fibroblast growth factor 3 (FGFR3) gene.
  • Other Likely diagnoses:
    • A) Cartilage oligometric matrix protein: This is associated with pseudoachondroplasia, a condition that also presents with short-limbed dwarfism and joint abnormalities, but the X-ray findings and clinical presentation are not as typical as those seen in achondroplasia.
    • E) Type 2 collagen: Defects in type 2 collagen are associated with various forms of spondyloepiphyseal dysplasia and Kniest dysplasia, which can present with short stature and skeletal abnormalities, but the specific X-ray findings and clinical features described are more characteristic of achondroplasia.
  • Do Not Miss (ddxs that may not be likely, but would be deadly if missed.):
    • D) Type 1 collagen: While osteogenesis imperfecta (caused by defects in type 1 collagen) primarily presents with bone fragility and blue sclerae, some types can have a more mild presentation with short stature and skeletal deformities. Missing this diagnosis could lead to inadequate management of fracture risk and other complications.
  • Rare diagnoses:
    • C) Sulfate transport protein: This is associated with diastrophic dysplasia, a rare form of short-limbed dwarfism with distinct clinical and radiographic features, including hitchhiker thumb and cystic changes in the ears. The presentation described does not closely match diastrophic dysplasia, making it a less likely consideration.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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