2. introduction
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.
3. cause
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. 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 1, is
very similar to boomerang dysplasia, and several symptoms
of both often overlap.
4. genetics
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.
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.
5. phenotypes
Affected individuals are born with inward- and upward-turning
feet (clubfeet) and dislocations of the hips, knees, and elbows.
Bones in the spine, rib cage, pelvis, and limbs may be
underdeveloped or in some cases absent. As a result of the
limb bone abnormalities, individuals with this condition have
very short arms and legs. Pronounced bowing of the upper leg
bones (femurs) gives them a "boomerang" shape.
Some individuals with boomerang dysplasia have a sac-like
protrusion of the brain (encephalocele). They may also have
an opening in the wall of the abdomen (an omphalacele) that
allows the abdominal organs to protrude through the navel.
Affected individuals typically have a distinctive nose that is
broad with very small nostrils and an underdeveloped
partition between the nostrils (septum).
Individuals with boomerang dysplasia typically have an
underdeveloped rib cage that affects the development and
functioning of the lungs. As a result, affected individuals are
usually stillborn or die shortly after birth from respiratory
failure.
