Boomerang dysplasia

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{{cite journal |vauthors=Winship I, Cremin B, Beighton P |title=Boomerang dysplasia |journal=Am J Med Genet |volume=36 |issue=4 |pages=440–443 |year=1990 |pmid=2202214 |doi=10.1002/ajmg.1320360413 |s2cid=38128867 }} (a lethal type of infantile dwarfism caused by systemic bone deformities),{{cite journal |vauthors=Kozlowski K, Tsuruta T, Kameda Y, Kan A, Leslie G |s2cid=31143908 |title=New forms of neonatal death dwarfism. Report of 3 cases |journal=Pediatr Radiol |volume=10 |issue=3 |pages=155–160 |year=1981 |pmid=7194471 |doi=10.1007/BF00975190 }} 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),{{cite journal |vauthors=Urioste M, Rodriguez JL, Bofarull J, Toran N, Ferrer C, Villa A |title=Giant-cell chondrocytes in a male infant with clinical and radiological findings resembling the Piepkorn type of lethal osteochondrodysplasia |journal=Am J Med Genet |volume=68 |issue=3 |pages=342–346 |year=1997 |pmid=9024569 |doi=10.1002/(SICI)1096-8628(19970131)68:3<342::AID-AJMG17>3.0.CO;2-T }} 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.{{cite journal |doi=10.1259/0007-1285-58-688-369 |vauthors=Kozlowski K, Sillence D, Cortis-Jones R, Osborn R |title=Boomerang dysplasia |journal=Br J Radiol |volume=58 |issue= 688|pages=369–371 |year=1985 |pmid=4063680 }} 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.{{cite journal |vauthors=Lu J, Lian G, Lenkinski R, De Grand A, Vaid RR, Bryce T, Stasenko M, Boskey A, Walsh C, Sheen V |title=Filamin B mutations cause chondrocyte defects in skeletal development |journal=Hum Mol Genet |volume=16 |issue=14 |pages=1661–1675 |year=2007 |pmid=17510210 |doi=10.1093/hmg/ddm114 |doi-access=free }} Disruptions in this pathway, caused by FLNB mutations, result in the bone and cartilage abnormalities associated with boomerang dysplasia.{{citation needed|date=June 2020}}

Chondrocytes, which also have a role in bone development, are susceptible to these disruptions and either fail to undergo ossification, or ossify incorrectly.

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.{{cite journal |vauthors=Greally MT, Jewett T, ((Smith WL Jr)), Penick GD, Williamson RA |title=Lethal bone dysplasia in a fetus with manifestations of Atelosteogenesis type I and Boomerang dysplasia |journal=Am J Med Genet |volume=47 |issue=4 |pages=1086–1091 |year=1993 |pmid=8291529 |doi=10.1002/ajmg.1320470731 }}

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.{{cite journal |vauthors=Nishimura G, Horiuchi T, Kim OH, Sasamoto Y |title=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 |journal=Am J Med Genet |volume=73 |issue=2 |pages=132–138 |year=1997 |pmid=9409862 |doi=10.1002/(SICI)1096-8628(19971212)73:2<132::AID-AJMG6>3.0.CO;2-W }}

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.{{Cite web| url = http://ghr.nlm.nih.gov/condition/boomerang-dysplasia| title = Boomerang dysplasia| date = 2016-02-22| website = Genetics Home Reference| access-date = 2016-03-01}}

Boomerang dysplasia, although an autosomal dominant disorder, is not inherited because those afflicted do not live beyond infancy. They cannot pass the gene to the next generation.{{cn|date=September 2021}}

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• Larsen syndrome

{{Reflist}}

{{Medical resources

| DiseasesDB =

| ICD10 = {{ICD10|Q|68|5|q|68}}

| ICD9 = {{ICD9|754.44}}

| ICDO =

| OMIM = 112310

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeshID =

| SNOMED CT = 254054000

| Orphanet = 1263

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{{Osteochondrodysplasia}}

{{Cytoskeletal defects}}

Category:Congenital disorders

Category:Rare diseases

Category:Autosomal dominant disorders