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Disease Profile

Atelosteogenesis type 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q78.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

AOI; Giant cell chondrodysplasia; Spondylohumerofemoral hypoplasia

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1190

Definition
A Pierre Robin syndrome associated with bone disease characterized by severe short-limbed dwarfism, joint dislocations, club feet along with distinctive facies and radiographic findings.

Epidemiology
Atelosteogenesis I (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.

Etiology
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 ribpolydactyly syndrome, and thanatophoric dysplasia. Other, differential diagnosis includes achondrogenesis, hypophosphatasia, and osteogenesis imperfecta.

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

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Abnormal ossification involving the femoral head and neck
0009107
Abnormality of fibula morphology
Abnormality of the calf bone
0002991
Absent or minimally ossified vertebral bodies
0004599
Brachydactyly
Short fingers or toes
0001156
Coronal cleft vertebrae
0003417
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Pulmonary hypoplasia
Small lung
Underdeveloped lung

[ more ]

0002089
Rhizomelia
Disproportionately short upper portion of limb
0008905
Short femur
Short thighbone
0003097
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
5%-29% of people have these symptoms
Abnormal pancreatic duct morphology
0030992
Cleft palate
Cleft roof of mouth
0000175
Enlarged cisterna magna
0002280
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Laryngotracheal stenosis
0004894
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Malrotation of colon
0004785
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Multiple renal cysts
Multiple kidney cysts
0005562
Neonatal short-trunk short stature
0008857
Platyspondyly
Flattened vertebrae
0000926
Polyhydramnios
High levels of amniotic fluid
0001561
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Retinal dysplasia
0007973
Scoliosis
0002650
Telecanthus
Corners of eye widely separated
0000506
Percent of people who have these symptoms is not available through HPO
11 pairs of ribs
0000878
Aplasia/Hypoplasia of the ulna
Absence/underdevelopment of inner forearm bone
0006495
Autosomal dominant inheritance
0000006
Clubbing
Clubbing of fingers and toes
0001217
Club-shaped proximal femur
Club-shaped innermost end of thighbone
0006406
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Distal tapering femur
Tapering of outermost end of thighbone
0006408
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
Encephalocele
0002084
Fibular aplasia
Absent calf bone
0002990
Frontal bossing
0002007
Fused cervical vertebrae
Fused neck
0002949
Laryngeal stenosis
0001602
Malar flattening
Zygomatic flattening
0000272
Multinucleated giant chondrocytes in epiphyseal cartilage
0030330
Neonatal death
Neonatal lethal
0003811
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Radial bowing
Bowing of outer large bone of the forearm
0002986
Short humerus
Short long bone of upper arm
Short upper arms

[ more ]

0005792
Short metacarpal
Shortened long bone of hand
0010049
Short metatarsal
Short long bone of foot
0010743
Short neck
Decreased length of neck
0000470
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Sporadic
No previous family history
0003745
Stillbirth
Stillborn
0003826
Thoracic platyspondyly
0004592
Tibial bowing
Bowed shankbone
Bowed shinbone

[ more ]

0002982

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Atelosteogenesis type 1. Click on the link to view a sample search on this topic.