Atelosteogenesis type 1
What is Atelosteogenesis type 1?
Atelosteogenesis type 1 is a rare skeletal disorder that affects the development of bones throughout the body. Certain bones may be underdeveloped or absent including the long bones of the arms and legs (humeri and femurs), the spine (vertebrae), the rib cage, and the pelvis. The disorder can also cause incomplete hardening (ossification) of certain bones in the hand. As a result of improper bone development, individuals with this condition have very short arms and legs. Underdevelopment of the rib cage affects the development and function of the lungs. Infants are usually stillborn or pass away shortly after birth usually from breathing difficulties due to respiratory failure.
Synonyms
- Giant Cell Chondrodysplasia
- Spondylohumerofemoral Hypoplasia
Atelosteogenesis type 1 is a rare skeletal disorder that affects the development of bones throughout the body. Certain bones may be underdeveloped or absent including the long bones of the arms and legs (humeri and femurs), the spine (vertebrae), the rib cage, and the pelvis. The disorder can also cause incomplete hardening (ossification) of certain bones in the hand. As a result of improper bone development, individuals with this condition have very short arms and legs. Underdevelopment of the rib cage affects the development and function of the lungs. Infants are usually stillborn or pass away shortly after birth usually from breathing difficulties due to respiratory failure.
The exact prevalence and incidence of atelosteogenesis type 1 are unknown. Only around a few dozen affected individuals have been identified in the medical literature. The disorder affects males and females equally.
| Name | Abbreviation |
|---|---|
| Giant Cell Chondrodysplasia | AOI |
| Spondylohumerofemoral Hypoplasia | AOI |
Atelosteogenesis type 1 is caused by mutations in the gene encoding for filamin B (FLNB) located at chromosome 3. In all reported cases, these mutations occurred sporadically as new mutations, and are not inherited.
The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of threadlike structures, protein filaments, that gives structure to cells and allows them to change shape and move. Filamin B is critically important in the formation of the skeleton in the developing fetus. The FLNB gene mutations that cause atelosteogenesis type 1 result in the production of an abnormal protein.
Mutations in the FLNB gene can also cause other disorders including Boomerang dysplasia, atelosteogenesis type 3, Larsen syndrome, and spondylocarpotarsal synostosis syndrome. Some researchers believe that these disorders make up a spectrum of disease ranging from mild to severe.
Symptoms of atelosteogenesis type 1 include short long bones of the arms, absence or underdevelopment of the calf bone, short and abnormally formed long bones of the legs, abnormally segmented or fused neck vertebrae, and abnormal flattening of the thoracic bones. Additional skeletal abnormalities can occur including dislocations of the hip, knees and elbow joints, clubfeet, a narrow chest, and abnormalities of the ribs. Infants may have distinctive facial features including a small jaw (micrognathia), a depressed nasal bridge, and a cleft palate.
Affected infants are usually stillborn or pass away shortly after birth because of respiratory failure.
A diagnosis is made through identification of clinical characteristics and x-ray findings. Differential diagnosis of atelosteogenesis type 1 includes various other skeletal conditions associated with severe short-limbed dwarfism such as campomelic dysplasia, Ellis-van Creveld syndrome, achondroplasia, metatropic dysplasia, Roberts syndrome, short rib-polydactyly syndrome, and thanatophoric dysplasia.
Diagnostic tests for atelosteogenesis type 1 include x-rays of the skeleton. Distinctive findings include a severely flattened vertebrae; shortened, incomplete or absent arm and leg bones; underdeveloped pelvis and calf bones; and deficient in bone tissue formation of the fingers and toes. Molecular genetic testing, which can identify a mutation in the FLNB gene, can confirm a diagnosis.
Diagnosis is possible before birth based upon a prenatal ultrasound, which can detect bone dysplasia and other manifestations in the developing fetus. Prenatal ultrasound can play an important role in early detection and diagnosis. Prenatal ultrasound findings may include severe limb shortening and deficiency in bone tissue formation of the long bones, shortened flaring or absent arm and leg bones from 18 weeks onwards. Other skeletal abnormalities as well as some facial dysmorphic features may also be detectable.
There has not yet been a cure discovered for atelosteogenesis type 1. For newborns with atelosteogenesis type 1, palliative care is offered.
The prognosis is often poor. Atelosteogenesis type 1 is usually fatal in utero, stillborn or neonatal death due to respiratory distress, or death early in life.
Families affected by atelosteogenesis type 1 should receive psychosocial support.
Atelosteogenesis, Type 1. Online Mendelian Inheritance in Man (OMIM) website. http://www.omim.org/entry/108720
Atelosteogenesis Type 1. Genetic Home Reference website. http://ghr.nlm.nih.gov/condition/atelosteogenesis-type-1.
Farrington-Rock C, Firestein MH, Bicknell LS, et al. Mutations in two regions of FLNB result in atelosteogenesis I and III. Hum Mutat. 2006;27(7):705-710.
Jeon GW, Lee MN, Jung JM, et al. Identification of a de novo heterozygous missense FLNB mutation in lethal atelosteogenesis type I by exome sequencing. Ann Lab Med. 2014;34(2):134-138.
Li BC, Hogue J, Eilers M, et al. Clinical report: two patients with atelosteogenesis type I caused by missense mutations affecting the same FLNB residue. Am J Med Genet A. 2013;161A(3):619-625.
Robertson S. FLNB-Related Disorders. GeneReviews website. http://www.ncbi.nlm.nih.gov/books/NBK2534/.
Robertson S. Atelosteogenesis Type I. Orphanet website. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=1190. Updated July 2013.
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