Boomerang dysplasia
Encyclopedia
Boomerang dysplasia is a lethal form of osteochondrodysplasia
known for a characteristic congenital feature in which bone
s of the arm
s and leg
s 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
.
s is the delineating factor.
Featured symptoms of boomerang dysplasia include: dwarfism
(a lethal type of infant
ile dwarfism caused by systemic bone deformities
), underossification
(lack of bone formation) in the limbs
, spine
and ilium
(pelvis
); proliferation of multinucleated giant-cell chondrocyte
s (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 ulna
s and tibia
s. Another patient may present "boomerang" femora
, and an absent tibia
.
) gene cause boomerang dysplasia. FLNB is a cytoplasm
ic 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 mutation
s, result in the bone and cartilage abnormalities associated with boomerang dysplasia.
Chondrocyte
s, 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.
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.
Osteochondrodysplasia
Osteochondrodysplasia is a general term for a disorder of the development of bone and cartilage .-Achondroplasia:Achondroplasia is a type of autosomal dominant genetic disorder that is a common cause ofdwarfism...
known for a characteristic congenital feature in which bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s of the arm
Arm
In human anatomy, the arm is the part of the upper limb between the shoulder and the elbow joints. In other animals, the term arm can also be used for analogous structures, such as one of the paired forelimbs of a four-legged animal or the arms of cephalopods...
s and leg
Human leg
The human leg is the entire lower extremity or limb of the human body, including the foot, thigh and even the hip or gluteal region; however, the precise definition in human anatomy refers only to the section of the lower limb extending from the knee to the ankle.Legs are used for standing,...
s are malformed into the shape of a boomerang
Boomerang
A boomerang is a flying tool with a curved shape used as a weapon or for sport.-Description:A boomerang is usually thought of as a wooden device, although historically boomerang-like devices have also been made from bones. Modern boomerangs used for sport are often made from carbon fibre-reinforced...
. Death usually occurs in early infancy due to complications arising from overwhelming systemic bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
malformations.
Osteochondrodysplasias are skeletal disorders that cause malformations of both bone and cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
.
Characteristics
Prenatal and neonatal diagnosis of boomerang dysplasia includes several prominent features found in other osteochondrodysplasias, though the "boomerang" malformation seen in the long boneLong bone
The long bones are those that are longer than they are wide. They are one of five types of bones: long, short, flat, irregular and sesamoid. Long bones, especially the femur and tibia, are subjected to most of the load during daily activities and they are crucial for skeletal mobility. They grow...
s is the delineating factor.
Featured symptoms of boomerang dysplasia include: dwarfism
Dwarfism
Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....
(a lethal type of infant
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
ile dwarfism caused by systemic bone deformities
Osteochondrodysplasia
Osteochondrodysplasia is a general term for a disorder of the development of bone and cartilage .-Achondroplasia:Achondroplasia is a type of autosomal dominant genetic disorder that is a common cause ofdwarfism...
), underossification
Ossification
Ossification is the process of laying down new bone material by cells called osteoblasts. It is synonymous with bone tissue formation...
(lack of bone formation) in the limbs
Limb (anatomy)
A limb is a jointed, or prehensile , appendage of the human or other animal body....
, spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
and ilium
Ilium (bone)
The ilium is the uppermost and largest bone of the pelvis, and appears in most vertebrates including mammals and birds, but not bony fish. All reptiles have an ilium except snakes, although some snake species have a tiny bone which is considered to be an ilium.The name comes from the Latin ,...
(pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
); proliferation of multinucleated giant-cell chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s (cells that produce cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and play a role in skeletal development - chondrocytes of this type are rarely found in osteochondrodysplasias), brachydactyly
Brachydactyly
Brachydactyly , is a medical term which literally means "shortness of the fingers and toes" . The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an inherited, usually dominant trait...
(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
Radius
In classical geometry, a radius of a circle or sphere is any line segment from its center to its perimeter. By extension, the radius of a circle or sphere is the length of any such segment, which is half the diameter. If the object does not have an obvious center, the term may refer to its...
and fibula, with the "boomerang" formation found in both ulna
Ulna
The ulna is one of the two long bones in the forearm, the other being the radius. It is prismatic in form and runs parallel to the radius, which is shorter and smaller. In anatomical position The ulna is one of the two long bones in the forearm, the other being the radius. It is prismatic in form...
s and tibia
Tibia
The tibia , shinbone, or shankbone is the larger and stronger of the two bones in the leg below the knee in vertebrates , and connects the knee with the ankle bones....
s. Another patient may present "boomerang" femora
Femur
The femur , or thigh bone, is the most proximal bone of the leg in tetrapod vertebrates capable of walking or jumping, such as most land mammals, birds, many reptiles such as lizards, and amphibians such as frogs. In vertebrates with four legs such as dogs and horses, the femur is found only in...
, and an absent tibia
Tibia
The tibia , shinbone, or shankbone is the larger and stronger of the two bones in the leg below the knee in vertebrates , and connects the knee with the ankle bones....
.
Cause
Mutations in the Filamin B (FLNBFLNB
Filamin B, beta , also known as FLNB, is a human cytoplasmic protein. It 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...
) gene cause boomerang dysplasia. FLNB is a cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that regulates intracellular communication and signalling by cross-linking the protein actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
to allow direct communication between the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
and cytoskeletal network
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
, to control and guide proper skeletal development. Disruptions in this pathway, caused by FLNB mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s, result in the bone and cartilage abnormalities associated with boomerang dysplasia.
Chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s, which also have a role in bone development, are susceptible to these disruptions and either fail to undergo ossification
Ossification
Ossification is the process of laying down new bone material by cells called osteoblasts. It is synonymous with bone tissue formation...
, or ossify incorrectly.
FLNB mutations are involved in a spectrum of lethal bone dysplasias
Osteochondrodysplasia
Osteochondrodysplasia is a general term for a disorder of the development of bone and cartilage .-Achondroplasia:Achondroplasia is a type of autosomal dominant genetic disorder that is a common cause ofdwarfism...
. One such disorder, atelosteogenesis type I, is very similar to boomerang dysplasia, and several symptoms of both often overlap.
Genetics
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
inheritance
Inheritance
Inheritance is the practice of passing on property, titles, debts, rights and obligations upon the death of an individual. It has long played an important role in human societies...
, based on observation and family history. It was later discovered, however, that the disorder is actually caused by a sporadic genetic mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
fitting an autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
dominant
Dominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...
genetic profile.
Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
, 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.