Boomerang dysplasia is a lethal form of osteochondrodysplasia known for a characteristic congenital feature in which bones of the arms and legs are malformed into the shape of a boomerang. Death usually occurs in early infancy due to complications arising from overwhelming systemic bone malformations.
Osteochondrodysplasias are skeletal disorders that cause malformations of both bone and cartilage.
Prenatal and neonatal diagnosis of boomerang dysplasia includes several prominent features found in other osteochondrodysplasias, though the “boomerang” malformation seen in the long bones is the delineating factor.
Featured symptoms of boomerang dysplasia include: dwarfism (a lethal type of infantile dwarfism caused by systemic bone deformities), underossification (lack of bone formation) in the limbs, spine and ilium (pelvis); proliferation of multinucleated giant-cell chondrocytes (cells that produce cartilage and play a role in skeletal development – chondrocytes of this type are rarely found in osteochondrodysplasias), brachydactyly (shortened fingers) and micromelia (undersized, shortened bones).
The characteristic “boomerang” malformation presents intermittently among random absences of long bones throughout the skeleton, in affected individuals. For example, one individual may have an absent radius and fibula, with the “boomerang” formation found in both ulnas and tibias. Another patient may present “boomerang” femora, and an absent tibia.
Mutations in the Filamin B (FLNB) gene cause boomerang dysplasia. FLNB is a cytoplasmic protein that regulates intracellular communication and signalling by cross-linking the protein actin to allow direct communication between the cell membrane and cytoskeletal network, to control and guide proper skeletal development. Disruptions in this pathway, caused by FLNB mutations, result in the bone and cartilage abnormalities associated with boomerang dysplasia.
FLNB mutations are involved in a spectrum of lethal bone dysplasias. One such disorder, atelosteogenesis type I, is very similar to boomerang dysplasia, and several symptoms of both often overlap.
Early journal reports of boomerang dysplasia suggested X-linked recessive inheritance, based on observation and family history. It was later discovered, however, that the disorder is actually caused by a sporadic genetic mutation fitting an autosomal dominant genetic profile.
Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.
- Bicknell LS, Morgan T, Bonife L, Wessels MW, Bialer MG, Willems PJ, Cohen DH, Krakow D, Robertson SP (2005). “Mutations in FLNB cause boomerang dysplasia”. Am J Med Genet. 42 (7): e43. doi:10.1136/jmg.2004.029967. PMC . PMID 15994868.
- Wessels MW, Den Hollander NS, Dekrijger RR, Bonife L, Superti-Furga A, Nikkels PG, Willems PJ (2003). “Prenatal diagnosis of boomerang dysplasia”. Am J Med Genet A. 122 (2): 148–154. doi:10.1002/ajmg.a.20239. PMID 12955767.
- Winship I, Cremin B, Beighton P (1990). “Boomerang dysplasia”. Am J Med Genet. 36 (4): 440–443. doi:10.1002/ajmg.1320360413. PMID 2202214.
- Kozlowski K, Tsuruta T, Kameda Y, Kan A, Leslie G (1981). “New forms of neonatal death dwarfism. Report of 3 cases”. Pediatr Radiol. 10 (3): 155–160. doi:10.1007/BF00975190. PMID 7194471.
- Urioste M, Rodriguez JL, Bofarull J, Toran N, Ferrer C, Villa A (1997). “Giant-cell chondrocytes in a male infant with clinical and radiological findings resembling the Piepkorn type of lethal osteochondrodysplasia”. Am J Med Genet. 68 (3): 342–346. doi:10.1002/(SICI)1096-8628(19970131)68:3<342::AID-AJMG17>3.0.CO;2-T. PMID 9024569.
- Kozlowski K, Sillence D, Cortis-Jones R, Osborn R (1985). “Boomerang dysplasia”. Brit J Radiol. 58 (688): 369–371. doi:10.1259/0007-1285-58-688-369. PMID 4063680.
- Lu J, Lian G, Lenkinski R, De Grand A, Vaid RR, Bryce T, Stasenko M, Boskey A, Walsh C, Sheen V (2007). “Filamin B mutations cause chondrocyte defects in skeletal development”. Hum Mol Genet. 16 (14): 1661–1675. doi:10.1093/hmg/ddm114. PMID 17510210.
- Nishimura G, Horiuchi T, Kim OH, Sasamoto Y (1997). “Atypical skeletal changes in otopalatodigital syndrome type II: phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and lethal male phenotype of Melnick-Needles syndrome”. Am J Med Genet. 73 (2): 132–138. doi:10.1002/(SICI)1096-8628(19971212)73:2<132::AID-AJMG6>3.0.CO;2-W. PMID 9409862.
- Greally MT, Jewett T, Smith WL Jr, Penick GD, Williamson RA (1993). “Lethal bone dysplasia in a fetus with manifestations of Atelosteogenesis type I and Boomerang dysplasia”. Am J Med Genet. 47 (4): 1086–1091. doi:10.1002/ajmg.1320470731. PMID 8291529.
- “Boomerang dysplasia”. Genetics Home Reference. 2016-02-22. Retrieved 2016-03-01.