Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: clues from the BMP signaling pathway.
METHODS
A radiographic analysis of the cervical spine of 70 patients diagnosed with fibrodysplasia ossificans progressiva (FOP) and 33 diagnosed with Klippel-Feil (KF) syndrome was conducted.


OBJECTIVE
The objectives of this study were to describe cervical spine abnormalities in patients with FOP, to compare and contrast those findings with the malformations in patients with KF syndrome, and to examine the possible etiology of these abnormalities.


BACKGROUND
Congenital features of diseases often provide seminal clues to underlying etiology and developmental pathways. While progressive metamorphosis of connective tissue to heterotopic bone is the most dramatic and disabling feature of FOP, less severe congenital anomalies of the skeleton are also present. Vertebral fusions observed in KF are consistent with defects in embryonic segmentation.


METHODS
The cervical spine plain films of 70 FOP patients and 33 KF patients with documented congenital abnormalities were reviewed.


RESULTS
Generalized neck stiffness and decreased range of motion were noted in most children with FOP. In the FOP patient group, characteristic anomalies, including large posterior elements, tall narrow vertebral bodies,and fusion of the facet joints between C2 and C7, were observed. Most notably, these characteristic anomalies of the cervical spine in patients with FOP were distinctly different from those of 33 patients with KF that were examined but were strikingly similar to those seen in mice with homozygous deletions of the gene-encoding noggin, a bone morphogenetic protein (BMP) antagonist.


CONCLUSIONS
FOP patients exhibit a characteristic set of congenital spine malformations. While the noggin gene (NOG) is not mutated in patients who have FOP, these findings extend a growing body of evidence implicating overactivity of the BMP signaling pathway in the molecular pathogenesis of FOP.
Schaffer
Alyssa A
AA
Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Institution B, Philadelphia, PA, USA.
Kaplan
Frederick S
FS
Tracy
Michael R
MR
O'Brien
Megan L
ML
Dormans
John P
JP
Shore
Eileen M
EM
Harland
Richard M
RM
Kusumi
Kenro
K
D000293:Adolescent; D000328:Adult; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002574:Cervical Vertebrae / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D007714:Klippel-Feil Syndrome / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009127:Muscle Rigidity / Q000209:etiology / Q000503:physiopathology; D009221:Myositis Ossificans / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016059:Range of Motion, Articular; D015398:Signal Transduction; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein