SOX9 gene anomalies and campomelic / acampomelic campomelic dysplasia: case report and literature review

Campomelic dysplasia (CD) is a rare skeletal disorder characterized by the hallmark sign of bent femur or tibial bones or both. Subsequently, patients were identified as having features of CD but lacking the bent limbs. This constellation was later described as acampomelic campomelic dysplasia (ACD). Both CD and ACD are caused by anomalies in the <i>SOX9</i> gene. Historically, CD has a high mortality rate, and ACD patients are often described similarly. Parents may be counseled to consider pregnancy termination or palliative care. This manuscript describes an index patient with ACD who exhibits prolonged survival, along with an extensive literature review. This review shows that roughly 9 out of 10 cases of acampomelic campomelic dysplasia with a genetic diagnosis survive beyond 1 year of age, most of whom are over 2 years old. In stark contrast, only approximately 3 out of 10 CD cases with a genetic diagnosis survive infancy. However, this CD number is skewed because survival beyond infancy is 2 in 10 or less for splice-site and nonsense pathologic variants, deletions, and insertions; approximately 4 in 10 cases for missense pathologic variants; and approximately 8 in 10 cases for chromosome 17 structural rearrangements. These findings are of critical importance for patient counseling and perinatal care planning.