Bent Bone Dysplasia Syndrome

A number sign (#) is used with this entry because of evidence that bent bone dysplasia syndrome (BBDS) is caused by heterozygous mutation in the FGFR2 gene (176943) on chromosome 10q26.

Clinical Features

Merrill et al. (2012) studied 4 fetuses, 3 female and 1 male, with 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. Dysmorphic facial features included 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.

Molecular Genetics

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.'