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Atelosteogenesis type I

Synonym(s) AO1
Atelosteogenesis type 1
Giant cell chondrodysplasia
Spondylo-humero-femoral dysplasia
Prevalence <1 / 1 000 000
Inheritance Autosomal dominant
Age of onset Neonatal
  • Q78.8
  • C0265283
  • C535396
MedDRA -


Disease definition

Atelosteogenesis I is a perinatally lethal skeletal dysplasia characterized by severe short-limbed dwarfism, joint dislocations, club feet along with distinctive facies and radiographic findings.


AOI is a very rare infrequently described disorder.

Clinical description

Affected neonates are stillborn or die rapidly after birth and present clinically with severe short-limbed dwarfism, dislocated hip, knee and elbow joints, club feet and if born alive have cardiorespiratory failure. Craniofacial dysmorphism describes a prominent forehead, hypertelorism, a depressed nasal bridge with a grooved tip, micrognathia and frequently a cleft palate. There is a continuum with overlapping clinical findings between atelosteogenesis I, atelosteogenesis III and boomerang dysplasia (see these terms).


Atelosteogenesis I results from heterozygous mutations in exons 2-5 and 27-33 of the gene encoding filamin B (FLNB) located to 3p14.

Diagnostic methods

'Diagnosis can be confirmed from skeletal radiographs, chondro-osseous histopathology and genetic testing. Distinctive radiographic findings comprise severe platyspondyly, distally tapered; shortened, incomplete or absent humeri and femurs; shortened or bowed radii, ulnas, and tibias; hypoplastic pelvis and fibulas; and deficient ossification of the metacarpals, middle and proximal phalanges.'

Differential diagnosis

Differential diagnosis comprises other skeletal dysplasias 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.. Other, differential diagnosis includes achondrogenesis, hypophosphatasia, and osteogenesis imperfecta (see these terms).

Antenatal diagnosis

Prenatal ultrasound can detect bone dysplasia and other manifestation and plays an important role in early detection and diagnosis. Prenatal ultrasound findings for AOI may include severe limb shortening and deficient ossification of the long bones, shortened flaring or absent humeri and femurs from 18 weeks onwards. Other skeletal abnormalities as well as some facial dysmorphic features may be detectable.

Genetic counseling

All cases have been autosomal dominant and sporadic resulting from de novo mutations in FLNB.

Management and treatment

Palliative care is offered to newborns suffering from AOI.


Prognosis is poor. Death is often due to a combination of pulmonary hypoplasia and tracheobronchomalacia early in life.

Expert reviewer(s)

  • Pr Stephen ROBERTSON

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Detailed information

Clinical genetics review
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