Atelosteogenesis type I is a rare autosomal dominant condition.Sillence D, Worthington S, Dixon J, Osborn R, Kozlowski K (1997) Atelosteogenesis syndromes: a review, with comments on their pathogenesis. Pediatr Radiol 27(5):388-396 This condition is evident at birth and is associated with a very poor prognosis for the baby. It may be diagnosed antenatally.

Signs and symptoms

Clinical features includeTemple K, Hall C A, Chitty L, Baraitser M (1990) A case of atelosteogenesis. J Med Genet 27: 194-197 * Abnormal facies **Prominent forehead **

Hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as ...

**Depressed nasal bridge with a grooved tip **

Micrognathia Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorma ...

Cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The t ...

* Severe short limbed dwarfism * Joint dislocations (

hip In vertebrate anatomy, hip (or "coxa"Latin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) in medical terminology) refers to either an anatomical region or a joint. The hip region ...

knee In humans and other primates, the knee joins the thigh with the human leg, leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest join ...

and

elbow The elbow is the region between the arm and the forearm that surrounds the elbow joint. The elbow includes prominent landmarks such as the olecranon, the cubital fossa (also called the chelidon, or the elbow pit), and the lateral and the m ...

joints) *

Club feet Club may refer to: Arts, entertainment, and media * ''Club'' (magazine) * Club, a '' Yie Ar Kung-Fu'' character * Clubs (suit), a suit of playing cards * Club music * "Club", by Kelsea Ballerini from the album ''kelsea'' Brands and enterprises ...

* Cardiorespiratory failure Cardiorespiratory failure is due to

pulmonary hypoplasia Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that ...

or tracheobronchial hypoplasia.Wessels A, Wainwright HC, Beighton P (2011) Atelosteogenesis type I: autopsy findings. Pediatr Dev Pathol 14(6):496-500

Genetics

This condition is caused by mutations in the filamin B (

FLNB Filamin B, beta (FLNB), also known as Filamin B, beta (truncated actin binding protein 278 homolog), is a cytoplasmic protein which in humans is encoded by the ''FLNB'' gene. FLNB regulates intracellular communication and signalling by cross-linki ...

) gene.Farrington-Rock C, Firestein MH, Bicknell LS, Superti-Furga A, Bacino CA, Cormier-Daire V, Le Merrer M, Baumann C, Roume J, Rump P, Verheij JB, Sweeney E, Rimoin DL, Lachman RS, Robertson SP, Cohn DH, Krakow D (2006) Mutations in two regions of FLNB result in atelosteogenesis I and III. Hum Mutat 27(7):705-710Li BC, Hogue J, Eilers M, Mehrotra P, Hyland J, Holm T, Prosen T, Slavotinek AM (2013) Clinical report: Two patients with atelosteogenesis type I caused by missense mutations affecting the same FLNB residue. Am J Med Genet A 161A(3):619-625. doi: 10.1002/ajmg.a.35792Jeon GW, Lee MN, Jung JM, Hong SY, Kim YN, Sin JB, Ki CS (2014) Identification of a de novo heterozygous missense FLNB mutation in lethal atelosteogenesis type I by exome sequencing. Ann Lab Med 34(2):134-138. doi: 10.3343/alm.2014.34.2.134 This gene is located on the short arm of

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA i ...

(3p14).

Pathogenesis

Filamin B forms part of the

actin Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is comp ...

. How these mutations produce the clinical picture is not yet clear.

Diagnosis

This condition is evident at birth and may be diagnosed antenatally with ultrasound or magnetic resonance imaging. The infants may be still born. Those that are live born do not survive long.Stevenson RE, Wilkes G (1983) Atelosteogenesis with survival beyond the neonatal period. Proc. Greenwood Genet Center 2: 32-38 Radiological findings includeUeno K, Tanaka M, Miyakoshi K, Zhao C, Shinmoto H, Nishimura G, Yoshimura Y (2002) Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation. Prenat Diagn 22(12):1071-1075 * Severe

platyspondyly Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condi ...

* Distally tapered, shortened, incomplete or absent

humeri The humerus (; ) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius and ulna, and consists of three sections. The humeral upper extremity consists of a roun ...

and

femur The femur (; ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates wit ...

s * Shortened or bowed radii,

ulna The ulna (''pl''. ulnae or ulnas) is a long bone found in the forearm that stretches from the elbow to the smallest finger, and when in anatomical position, is found on the medial side of the forearm. That is, the ulna is on the same side of t ...

s and

tibia The tibia (; ), also known as the shinbone or shankbone, is the larger, stronger, and anterior (frontal) of the two bones in the leg below the knee in vertebrates (the other being the fibula, behind and to the outside of the tibia); it connects ...

s * Hypoplastic pelvis and

fibula The fibula or calf bone is a human leg, leg bone on the Lateral (anatomy), lateral side of the tibia, to which it is connected above and below. It is the smaller of the two bones and, in proportion to its length, the most slender of all the long ...

s * Deficient ossification of the

metacarpal In human anatomy, the metacarpal bones or metacarpus form the intermediate part of the skeletal hand located between the phalanges of the fingers and the carpal bones of the wrist, which forms the connection to the forearm. The metacarpal bones ...

s, middle and proximal

phalange The phalanges (singular: ''phalanx'' ) are digital bones in the hands and feet of most vertebrates. In primates, the thumbs and big toes have two phalanges while the other digits have three phalanges. The phalanges are classed as long bones ...

Differential diagnosis

This includesNishimura 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 *

Achondroplasia Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected ha ...

Achondrogenesis Achondrogenesis is a number of disorders that are the most severe form of congenital chondrodysplasia (malformation of bones and cartilage). These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a r ...

* Atelosteogenesis III *

Boomerang dysplasia 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 ...

Campomelic dysplasia Campomelic dysplasia (CMD) is a genetic disorder characterized by bowing of the long bones and many other skeletal and extraskeletal features. It can be lethal in the neonatal period due to respiratory insufficiency, but the severity of the diseas ...

* Ellis–Van Creveld syndrome *

Hypophosphatasia Hypophosphatasia (; also called deficiency of alkaline phosphatase, phosphoethanolaminuria, or Rathbun's syndrome; sometimes abbreviated HPP) is a rare, and sometimes fatal, inherited metabolic bone disease. Clinical symptoms are heterogeneous, ...

* Melnick Needles syndrome *

Metatropic dysplasia Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...

Osteogenesis imperfecta Osteogenesis imperfecta (; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily. The range of symptoms—on the skeleton as well as on the body's other organs—may b ...

Roberts syndrome Roberts syndrome, or sometimes called pseudothalidomide syndrome, is an extremely rare autosomal recessive genetic disorder that is characterized by mild to severe prenatal retardation or disruption of cell division, leading to malformation of th ...

* Short-rib polydactyly syndrome *

Thanatophoric dysplasia Thanatophoric dysplasia is a severe skeletal disorder characterized by a disproportionately small ribcage, extremely short limbs and folds of extra skin on the arms and legs. Symptoms and signs Infants with this condition have disproportionately ...

Treatment

There is currently no curative treatment for this condition. Supportive management is all that is currently available.

Epidemiology

This is a rare condition with a prevalence of less than 1/10⁶. The total number of cases reported to date is less than 20.

History

This condition was first described by Maroteaux et al. in 1982.Maroteaux P, Spranger J, Stanescu V, Le Marec B, Pfeiffer RA, Beighton P, Mattei JF (1982) Atelosteogenesis. Am J Med Genet 13: 15-25

References

{{Medical resources , DiseasesDB = , ICD10 = , ICD9 = , ICDO = , OMIM = 108720 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = , GeneReviewsNBK = , GeneReviewsName = Genetic diseases and disorders Rare diseases