Alternative titles; symbols
ORPHA: 313855, 93439; DO: 0060992, 10591;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q26.13 | Bent bone dysplasia syndrome | 614592 | Autosomal dominant | 3 | FGFR2 | 176943 |
A number sign (#) is used with this entry because of evidence that bent bone dysplasia syndrome-1 (BBDS1) is caused by heterozygous mutation in the FGFR2 gene (176943) on chromosome 10q26.
Bent bone dysplasia syndrome-1 (BBDS1) is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones (Merrill et al., 2012).
Genetic Heterogeneity of Bent Bone Dysplasia Syndrome
BBDS2 (620076) is caused by mutation in the LAMA5 gene (601033) on chromosome 20q13.
Merrill et al. (2012) reported 4 fetuses, 3 female and 1 male, with bent bone dysplasia syndrome and mutation in the FGFR2 gene. Examination revealed dysmorphic facial features including low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia. The 3 female fetuses all displayed clitoromegaly, and 1 had hepatosplenomegaly with extramedullary hematopoiesis that was noted at autopsy. Radiographic findings included bent long bones, particularly involving the femora; osteopenia; irregular periosteal surfaces, especially in the phalanges; deficient skull ossification; coronal craniosynostosis; and hypoplastic clavicles and pubis. Histologic analysis of the distal femoral growth plate from 2 fetuses showed that the growth plate contained smaller hypertrophic chondrocytes compared to a control, and there was a thickened, hypercellular periosteum.
The heterozygous mutations in the FGFR2 gene that were identified in fetuses with BBDS1 by Merrill et al. (2012) occurred de novo.
Merrill et al. (2012) analyzed 6 candidate genes in 3 female fetuses and 1 male fetus with a perinatal lethal bent bone dysplasia syndrome and identified heterozygosity for the same de novo missense mutation in the FGFR2 gene in 3 of them (M391R; 176943.0043), with a different heterozygous FGFR2 mutation detected in the remaining fetus (Y381D; 176943.0044). Merrill et al. (2012) stated that the clinical and genetic findings of the 4 fetuses constituted a distinct disorder, which they designated 'bent bone dysplasia (BBD)-FGFR2 type.'
Merrill, A. E., Sarukhanov, A., Krejci, P., Idoni, B., Camacho, N., Estrada, K. D., Lyons, K. M., Deixler, H., Robinson, H., Chitayat, D., Curry, C. J., Lachman, R. S., Wilcox, W. R., Krakow, D. Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling. Am. J. Hum. Genet. 90: 550-557, 2012. [PubMed: 22387015] [Full Text: https://doi.org/10.1016/j.ajhg.2012.02.005]