National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Achondrogenesis


Categories:
Subtypes:
Achondrogenesis type 1A; Achondrogenesis type 1B; Achondrogenesis type 2
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]  
Last updated: 10/18/2018
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]
Last updated: 10/18/2018

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.

Showing of 59 |
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 hand bone ossification 0010660
Abnormality of the femoral metaphysis 0006489
Abnormality of the foot
Abnormal feet morphology
Abnormality of the feet
Foot deformities
Foot deformity
[ more ] 		0001760
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 0004606
Showing of 59 |
Last updated: 7/1/2020
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]

Last updated: 10/18/2018
Achondrogenesis type 1A and type 1B are believed to be inherited in an autosomal recessive pattern.[1][2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this condition.

Infants with achondrogenesis inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% chance to be affected
  • 50% chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not a carrier
Achondrogenesis type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is caused by a new (de novo) mutation and usually occurs in people with no history of the disorder in their family.[1][2][5] There are rare cases of families who have had more than one pregnancy with achondrogenesis type 2.[5] These cases are thought to occur because of mosaicism, which means that a portion of the DNA in a person's cells is different than the DNA in the rest of his/her body. Germline mosaicism occurs then a person's reproductive cells (sperm or egg) carry a mutation not found in the rest of the cells in the body. Somatic mosaicism occurs when a person has a some body cells that carry a mutation and some body cells that do not carry the mutation. Individuals with germline or somatic mosaicism are generally healthy and do not show signs of the disorder. 
Last updated: 10/18/2018
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.
Last updated: 10/18/2018

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.
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]
Last updated: 10/18/2018
Most infants with achondrogenesis have severely underdeveloped lungs which leads to serious breathing problems and lung failure. Most die before or shortly after birth because of the severity of this disorder.[1][2]   
Last updated: 10/18/2018
Achondrogenesis affects males and females in equal numbers. Achondrogenesis type 1A and type 1B are very rare disorders and the prevalence for them is unknown.  Achondrogenesis type 2 occurs in approximately 1/40,000-1/60,000 newborns.[1][2]
Last updated: 10/18/2018

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Achondrogenesis. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Achondrogenesis:
    International Skeletal Dysplasia Registry (ISDR)
     

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

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

  • Genetics Home Reference (GHR) contains information on Achondrogenesis. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • 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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Achondrogenesis. Genetics Home Reference. February, 2008; updated Mar 2015; http://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.