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Disease Profile

Atelosteogenesis type 3

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

Infancy

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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)

AOIII; AO3

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: 56305

Definition
A rare skeletal dysplasia characterized by short limbs dysmorphic facies and diagnostic radiographic findings.

Epidemiology
The prevalence of AOIII is unknown. Less than 25 affected patients have been reported.

Clinical description
AOII, like AOI, is characterized by rhizomelic limb shortness, dislocated hip, knee and elbow joints, broad hands and feet with broad digits, club feet, facial dysmorphism (midface hypoplasia, micrognathia, cleft palate). Feeding problems and cardiorespiratory insufficiency are often seen in newborns. Clinical manifestations due to secondary complications past early infancy include learning and language problems and a gross motor developmental delay.

Etiology
Atelosteogenesis III results from missense mutations or small in-frame deletions in the FLNB gene reported in exons 2-5, 13 and 27-33 resulting in the translation of filamin B protein with altered biochemical properties.

Diagnostic methods
The diagnosis is established after a full skeletal x-ray survey and confirmed with genetic testing. AOIII demonstrates less delay of normal ossification compared to AOI.

Antenatal diagnosis
Prenatal diagnosis is possible by ultrasound from 20 weeks onward and by prenatal genetic testing in case of family history.

Genetic counseling
Most cases of AOIII are sporadic, but AOIII may be transmitted in an autosomal dominant manner. Affected individuals of which one of the parents presents with a milder phenotype (like Larsen syndrome) (see this term) have been reported. This is likely to be related to a somatic mosaicism in the parents for a mutation that is germline in the offspring.

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
Coronal cleft vertebrae
0003417
Distal tapering femur
Tapering of outermost end of thighbone
0006408
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Knee dislocation
0004976
Patellar dislocation
Dislocated kneecap
0002999
Respiratory insufficiency
Respiratory impairment
0002093
Short tubular bones of the hand
0001248
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Vertebral hypoplasia
Underdeveloped vertebrae
0008417
5%-29% of people have these symptoms
Abnormal cervical curvature
Abnormal neck curve
0005905
Absent humerus
Absent long bone in upper arm
0003862
Absent radius
Missing outer large bone of forearm
0003974
Club-shaped distal femur
Club-shaped outermost end of thighbone
0006384
Epiphyseal stippling of the humerus
0003902
Fibular aplasia
Absent calf bone
0002990
Global developmental delay
0001263
Hand clenching
Clenched hands
0001188
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Laryngotracheomalacia
0008755
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Polyhydramnios
High levels of amniotic fluid
0001561
Short tibia
Short shinbone
Short skankbone

[ more ]

0005736
Thoracic hypoplasia
Small chest
Small thorax

[ more ]

0005257
Thoracolumbar kyphosis
0005619
Ulnar deviation of the wrist
0003049
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Cervical kyphosis
Rounded neck
0002947
Cervical segmentation defect
0004632
Cleft palate
Cleft roof of mouth
0000175
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
Flat acetabular roof
0003180
Frontal bossing
0002007
Hitchhiker thumb
0001234
Horizontal sacrum
0003440
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Malar flattening
Zygomatic flattening
0000272
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Radial bowing
Bowing of outer large bone of the forearm
0002986
Rhizomelia
Disproportionately short upper portion of limb
0008905
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe

[ more ]

0001852
Scoliosis
0002650
Short neck
Decreased length of neck
0000470
Tibial bowing
Bowed shankbone
Bowed shinbone

[ more ]

0002982
Tombstone-shaped proximal phalanges
Tombstone-shaped innermost digital bones
0006060
Widened distal phalanges
Widened outermost bone of limb
0006200

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

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

  • 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 3. Click on the link to view a sample search on this topic.