Angulated femurs and the skeletal dysplasias: Experience of the International Skeletal Dysplasia Registry (1988–2006)

Abstract

Angulated or bent femur (isolated or associated with other long bone bowing) in the fetus or newborn is relatively common when evaluating patients with skeletal dysplasias. To determine the extent and heterogeneity of disorders associated with angulated or bent femurs, we analyzed cases in the radiographic database (1998-2006) of the International Skeletal Dysplasia Registry (ISDR) and determined which established skeletal dysplasias and genetic syndromes are associated with this finding. The results show that more than 40 distinct disorders with varying frequency (very rare to more commonly occurring disorders) can be associated with bowed/bent/angulated femurs. Sixty-six percent of the cases with angulated femurs belonged to three well described groups of disorders; campomelic disorders (24.4%), thanatophoric dysplasia (23.9%) and osteogenesis imperfecta (OI) (18.1%). With specific emphasis on these, this cross-sectional cohort provides discussion of data on other rare disorders associated with angulated femurs and the importance of the finding relative to its occurrence within a diagnostic group. This study aims to provide differential diagnosis of entities to be considered when a fetus or newborn is found to have congenital bowing/angulation of the femur.

Phenotype of five cases of prenatally diagnosed campomelic dysplasia harboring novel mutations of the SOX9 gene

“…In the prenatal/perinatal form of osteogenesis imperfecta, bowed long bones occur as the result of fractures. In thanatophoric dysplasia Type I, the long tubular bones and the femur in particular are rather curved, resembling a ‘French telephone receiver’28. In these cases, ultrasound scans can be quite predictive, particularly in CD, as reported by Schramm et al in their recent paper9.…”

Stuve–Wiedemann syndrome: a skeletal dysplasia characterized by bowed long bones

“…In the Revised International Nosology and Classification of Genetic Disorders of Bone—200612, SWS has been classified under the bent skeletal dysplasias along with campomelic dysplasia (CMPD), Cumming syndrome and kyphomelic dysplasia17. Alternative diagnostic considerations in the setting of bowed femora and mild‐to‐moderate micromelia would be Antley–Bixler syndrome, femoral hypoplasia‐unusual facies syndrome (FH‐UFS), osteogenesis imperfecta (OI) and diastrophic dysplasia18–21. They can be diagnosed easily at birth based on clinical and radiological findings.…”

Stem cell transplantation before birth – a realistic option for treatment of osteogenesis imperfecta?

“…They affect approximately 2 to 5 per 10 000 live births. In various studies based on registers or autopsy material, the OI cases constitute approximately 20 to 25% of these cases . Several specific types of OI are defined according to genetic abnormality and phenotypic expression.…”