Am J Med Genet A. 2016 Oct;170(10):2652-61. doi: 10.1002/ajmg.a.37772. Epub 2016 May 30.

Clinical and radiographic delineation of Bent Bone Dysplasia-FGFR2 type or Bent Bone Dysplasia with Distinctive Clavicles and Angel-shaped Phalanges.

Krakow D^1,^2,^3,⁴, Cohn DH^5,^6,⁷, Wilcox WR^6,⁸, Noh GJ⁹, Raffel LJ⁹, Sarukhanov A⁵, Ivanova MH⁵, Danielpour M¹⁰, Grange DK¹¹, Elliott AM¹², Bernstein JA¹³, Rimoin DL, Merrill AE¹⁴, Lachman RS^6,¹⁵.

Author information

1: Department of Orthopaedic Surgery, University of California, Los Angeles, California. dkrakow@mednet.ucla.edu.
2: Department of Human Genetics, University of California, Los Angeles, California. dkrakow@mednet.ucla.edu.
3: Department of Obstetrics and Gynecology, University of California, Los Angeles, California. dkrakow@mednet.ucla.edu.
4: International Skeletal Dysplasia Registry, University of California, Los Angeles, California. dkrakow@mednet.ucla.edu.
5: Department of Orthopaedic Surgery, University of California, Los Angeles, California.
6: International Skeletal Dysplasia Registry, University of California, Los Angeles, California.
7: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, California.
8: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
9: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California.
10: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
11: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, Saint Louis, Missouri.
12: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia.
13: Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
14: Center for Craniofacial Molecular Biology-Ostrow School of Dentistry, Keck School of Medicine, University of Southern California, Los Angeles, California.
15: Department of Radiology, Stanford University School of Medicine, Stanford, California.

Abstract

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.