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Disease Profile

Achondrogenesis

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.

Unknown

Age of onset

Neonatal

ICD-10

Q77.0

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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Categories

Congenital and Genetic Diseases

Summary

Achondrogenesis is a group of severe disorders that are present from birth and affect the development of cartilage and bone. Infants with achondrogenesis usually have a small body, extremely short arms and legs, other skeletal abnormalities, and underdeveloped lungs.[1][2] There are at least three forms of achondrogenesis, type 1A, type 1B and type 2. Achondrogenesis is usually diagnosed during pregnancy by ultrasound and genetic testing is used to distinguish between the three types.[1][2] Type 1A and 1B achondrogenesis are both inherited in an autosomal recessive pattern. Type 1A is caused by mutations in the TRIP11 gene.[3] Type 1B is caused by mutations in the SLC26A2 gene.[4] Type 2 achondrogenesis is caused by new (de novo) mutations in the COL2A1 gene.[5] Because of the severity of this condition, most infants with achondrogenesis die before or shortly after birth.[1][2]

Symptoms

Infants with achondrogenesis have very short, underdeveloped arms and legs (micromelia), and a short trunk. The ribs, spine and skull are underdeveloped and poorly ossified, meaning that they are not hard like regular bone. The small rib cage leads to poorly formed lungs, and the chest appears small. Infants with achondrogenesis have relatively large stomachs and heads when compared to the rest of their body.[1][2]

All three types of achondrogenesis have similar features, and it can be difficult to tell the types apart based only on signs and symptoms. In general, infants with type 1A are more likely to have rib fractures, infants with type 1B may have short fingers and toes, and infants with type 2 have very soft hip bones and spinal column.[4]

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
80%-99% of people have these symptoms
Abnormal enchondral ossification
0003336
Abnormality of bone mineral density
0004348
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Aplasia/Hypoplasia of the lungs
Absent/small lungs
Absent/underdeveloped lungs

[ more ]

0006703
Flat face
Flat facial shape
0012368
Frontal bossing
0002007
Long philtrum
0000343
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Short neck
Decreased length of neck
0000470
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Short thorax
Shorter than typical length between neck and abdomen
0010306
Skeletal dysplasia
0002652
Thickened nuchal skin fold
Thickened skin folds of neck
Thickened skin over the neck

[ more ]

0000474
30%-79% of people have these symptoms
Inguinal hernia
0000023
Umbilical hernia
0001537
5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Cystic hygroma
0000476
Percent of people who have these symptoms is not available through HPO
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating

[ more ]

0003270
Abnormal foot bone ossification
0010675
Abnormal foot morphology
Abnormal feet structure
Abnormality of the feet
Abnormality of the foot
Foot deformities
Foot deformity

[ more ]

0001760
Abnormal hand bone ossification
0010660
Abnormality of the femoral metaphysis
0006489
Absent or minimally ossified vertebral bodies
0004599
Absent vertebral body mineralization
0004605
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Barrel-shaped chest
Barrel chest
0001552
Beaded ribs
0000923
Breech presentation
Feet or buttocks of fetus positioned near opening of uterus
0001623
Broad clavicles
Broad collarbone
0000916
Broad long bones
Wide long bones
Widened long bones

[ more ]

0005622
Cleft palate
Cleft roof of mouth
0000175
Decreased skull ossification
Decreased bone formation of skull
0004331
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
Disproportionate short-limb short stature
Short limb dwarfism, disproportionate
Short-limbed dwarfism

[ more ]

0008873
Disproportionate short-trunk short stature
Disproportionate short-trunked dwarfism
Disproportionate short-trunked short stature
Short-trunked dwarfism

[ more ]

0003521
Edema
Fluid retention
Water retention

[ more ]

0000969
Horizontal ribs
0000888
Hydrops fetalis
0001789
Hypoplasia of the radius
Underdeveloped outer large forearm bone
0002984
Hypoplastic ilia
0000946
Hypoplastic iliac wing
0002866
Hypoplastic ischia
0003175
Hypoplastic scapulae
Small shoulder blade
0000882
Malar flattening
Zygomatic flattening
0000272
Micromelia
Smaller or shorter than typical limbs
0002983
Neonatal short-limb short stature
Short limb dwarfism recognizable at birth
Short-limb dwarfism identifiable at birth
Short-limbed dwarfism identifiable at birth

[ more ]

0008921
Polyhydramnios
High levels of amniotic fluid
0001561
Protuberant abdomen
Belly sticks out
Extended belly

[ more ]

0001538
Respiratory insufficiency
Respiratory impairment
0002093
Short clavicles
Short collarbone
0000894
Short long bone
Long bone shortening
0003026
Short ribs
0000773
Short tubular bones of the hand
0001248
Stillbirth
Stillborn
0003826
Unossified vertebral bodies

Cause

Changes (mutations) in the TRIP11, SLC26A2 and COL2A1 genes cause achondrogenesis types 1A, 1B and 2, respectively. The TRIP11 gene provides instructions for making a protein that is involved in forming the Golgi body, an important structure found in most cells of the body. The SLC26A2 gene provides instructions for making a protein that is important for the normal development of cartilage and for the conversion of cartilage to bone. The COL2A1 gene provides instructions for making a protein that forms a type of collagen found mostly in cartilage and in the clear gel that fills the eyeball (vitreous). Mutations in these genes result in the production of proteins that are unable to properly perform their jobs within the body.[1][2]

Diagnosis

Achondrogenesis can be diagnosed during pregnancy by ultrasound as early as 12-14 weeks.[2][3] At birth, this condition is suspected when the infant has extremely short underdeveloped arms and legs, short ribs and small chest, and short trunk.  X-ray findings include underdeveloped skull, vertebrate and rib cage.[2] Genetic testing of the TRIP11, SLC26A2 and COL2A1 genes can be performed to confirm the diagnosis and determine the type of achondrogenesis.

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.

    Treatment

    Medical care for achondrogenesis is focused on addressing any symptoms and relieving pain. Genetic counseling is recommended for families with a diagnosis of achondrogenesis.[1][3]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Providing General Support

      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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Achondrogenesis. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        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.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • 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. 
          Achondrogenesis type 1A
          Achondrogenesis type 1B
          Achondrogenesis type 2
        • 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 Achondrogenesis. Click on the link to view a sample search on this topic.

          References

          1. Achondrogenesis. Genetics Home Reference. February, 2008; updated Mar 2015; https://ghr.nlm.nih.gov/condition/achondrogenesis. Accessed 10/15/2018.
          2. Achondrogenesis. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/achondrogenesis. Accessed 10/11/2018.
          3. Vanegas S, Sua LF, Lopez-Tenorio J. Ramirez-Montano D, Pachajoa H.. Achondrogenesis, type 1A: clinical, histologic, molecular and prenatal ultrasound diagnosis.. Appl Clin Genet.. 2018; 11:69-73. https://www.ncbi.nlm.nih.gov/pubmed/29872333.
          4. Bonafe L, Mittax-Crettol L, Balhausen D, Supreti-Furga A. Achondrogenesis, type 1B. GeneReviews. https://www.ncbi.nlm.nih.gov/books/NBK1516/. Accessed 10/15/2018.
          5. Comstock JM, Putnam AR, Sangle N, Lowichik A, Rose N, Optiz JM. Recurrence of Achondrogenesis type 2 in sibs: Additional evidence for germline mosaicism.. Am J Med Genet Part A. 2010; 152A:1822-1824. https://www.ncbi.nlm.nih.gov/pubmed/20583175.

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