TY - JOUR
T1 - Clinical and radiographic delineation of Bent Bone Dysplasia-FGFR2 type or Bent Bone Dysplasia with Distinctive Clavicles and Angel-shaped Phalanges
AU - Krakow, Deborah
AU - Cohn, Daniel H.
AU - Wilcox, William R.
AU - Noh, Grace J.
AU - Raffel, Leslie J.
AU - Sarukhanov, Anna
AU - Ivanova, Margarita H.
AU - Danielpour, Moise
AU - Grange, Dorothy K.
AU - Elliott, Alison M.
AU - Bernstein, Jonathan A.
AU - Rimoin, David L.
AU - Merrill, Amy E.
AU - Lachman, Ralph S.
N1 - Funding Information:
We thank the patients, families and referring physicians for allowing us to participate in their care and share their unique findings. This study was supported in part by grants from the National Institutes of Health (RO1 AR066124, R01 AR062651, R01 DE025222, and PO1 HD070394) to D.H.C and D.K in addition to support from the March of Dimes, the Joseph Drown Foundation and the Orthopaedic Institute for Children. A.E.M is supported by the March of Dimes Gene Discovery and Translation Research grant number #6-FY15-233 and the National Institute of Health R01 DE025222. We also thank Nicholas Batchelder for help building the tables.
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Bent Bone Dysplasia-FGFR2 type is a relatively recently described bent bone phenotype with diagnostic clinical, radiographic, and molecular characteristics. Here we report on 11 individuals, including the original four patients plus seven new individuals with three longer-term survivors. The prenatal phenotype included stillbirth, bending of the femora, and a high incidence of polyhydramnios, prematurity, and perinatal death in three of 11 patients in the series. The survivors presented with characteristic radiographic findings that were observed among those with lethality, including bent bones, distinctive (moustache-shaped) small clavicles, angel-shaped metacarpals and phalanges, poor mineralization of the calvarium, and craniosynostosis. Craniofacial abnormalities, hirsutism, hepatic abnormalities, and genitourinary abnormalities were noted as well. Longer-term survivors all needed ventilator support. Heterozygosity for mutations in the gene that encodes Fibroblast Growth Factor Receptor 2 (FGFR2) was identified in the nine individuals with available DNA. Description of these patients expands the prenatal and postnatal findings of Bent Bone Dysplasia–FGFR2 type and adds to the phenotypic spectrum among all FGFR2 disorders.
AB - Bent Bone Dysplasia-FGFR2 type is a relatively recently described bent bone phenotype with diagnostic clinical, radiographic, and molecular characteristics. Here we report on 11 individuals, including the original four patients plus seven new individuals with three longer-term survivors. The prenatal phenotype included stillbirth, bending of the femora, and a high incidence of polyhydramnios, prematurity, and perinatal death in three of 11 patients in the series. The survivors presented with characteristic radiographic findings that were observed among those with lethality, including bent bones, distinctive (moustache-shaped) small clavicles, angel-shaped metacarpals and phalanges, poor mineralization of the calvarium, and craniosynostosis. Craniofacial abnormalities, hirsutism, hepatic abnormalities, and genitourinary abnormalities were noted as well. Longer-term survivors all needed ventilator support. Heterozygosity for mutations in the gene that encodes Fibroblast Growth Factor Receptor 2 (FGFR2) was identified in the nine individuals with available DNA. Description of these patients expands the prenatal and postnatal findings of Bent Bone Dysplasia–FGFR2 type and adds to the phenotypic spectrum among all FGFR2 disorders.
KW - FGFR2
KW - bent bone dysplasia
KW - craniosynostosis
KW - skeletal dysplasia
UR - http://www.scopus.com/inward/record.url?scp=84988025462&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.37772
DO - 10.1002/ajmg.a.37772
M3 - Article
C2 - 27240702
AN - SCOPUS:84988025462
VL - 170
SP - 2652
EP - 2661
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 10
ER -