SOX9 Gene Defects and Campomelic / Acampomelic Campomelic Dysplasia: Case Report and Literature Review

Craig V Towers^1*John T Meadows²Peter T Petruzzi²Kelsey Leonard Grabeel³

• ¹High Risk Obstetrical Consultants, University of Tennessee Medical Center, Knoxville, United States
• ²The University of Tennessee Medical Center, Knoxville, United States
• ³The University of Tennessee Graduate School of Medicine, Knoxville, United States

Campomelic dysplasia (CD) is a rare skeletal disorder that has a hallmark sign of bent femur and/or tibial bones. 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 SOX9 gene anomalies. 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 that has 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 which are over age 2. In stark contrast, only about 3 in 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; about 4 in 10 for missense pathologic variants; but nearly 8 in 10 for chromosome 17 structural rearrangements. These findings are of extreme importance for patient counseling and perinatal care planning.