Genetics and Achondroplasia

Most people who have achondroplasia have average-size parents. In this situation, the FGFR3 gene mutation occurs in one parent's egg or sperm cell before conception. Other people with achondroplasia inherit the condition from a parent who has achondroplasia.

Source: NHGRI (NIH)1

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Back to: « Achondroplasia

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Is achondroplasia inherited?

Most cases of achondroplasia are not inherited. When achondroplasia is inherited, it is inherited in an autosomal dominant manner.

Over 80 percent of individuals who have achondroplasia have parents with normal stature and are born with achondroplasia as a result of a new (de novo) gene alteration (mutation). These parents have a small chance of having another child with achondroplasia.

A person who has achondroplasia who is planning to have children with a partner who does not have achondroplasia has a 50 percent chance, with each pregnancy, of having a child with achondroplasia. When both parents have achondroplasia, the chance for them, together, to have a child with normal stature is 25 percent. Their chance of having a child with achondroplasia is 50 percent. Their chance for having a child who inherits the gene mutation from both parents (called homozygous achondroplasia - a condition that leads to death) is 25 percent.

Source: NHGRI (NIH)2

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Although this condition can be inherited in an autosomal dominant manner, 80% of cases are due to new, sporadic mutations. Mutations involve the gene encoding fibroblast growth factor receptor 3 (FGFR3), situated on chromosome 4. Most commonly, a point mutation causes the substitution of arginine for glycine (G380R) in the transmembrane region of the receptor.

Source: NCBI, Genes and Disease (NCBI/NIH)3

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Genetic Changes

Mutations in the FGFR3 gene cause achondroplasia . The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia . Researchers believe that these mutations cause the FGFR3 protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth seen with this disorder.

Source: GHR (NLM/NIH)4

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Inheritance Pattern

Achondroplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 80 percent of people with achondroplasia have average-size parents; these cases result from new mutations in the FGFR3 gene. In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents . Individuals who inherit two altered copies of this gene typically have a severe form of achondroplasia that causes extreme shortening of the bones and an underdeveloped rib cage. These individuals are usually stillborn or die shortly after birth from respiratory failure.

Source: GHR (NLM/NIH)5

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Learn more about the gene associated with achondroplasia

  • FGFR3

Source: GHR (NLM/NIH)6

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Inheritance

Most cases of achondroplasia are not inherited.[3] When it is inherited, it follows an autosomal dominant pattern of inheritance. About 80% of individuals who have achondroplasia have parents with normal stature and are born with the condition as a result of a new (de novo) gene alteration (mutation).[1, 2][3] Each individual with achondroplasia has a 50% chance, with each pregnancy, to pass on the mutated gene.[2, 3] Last updated: 1/26/2016

Source: GARD (NIH)7

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Modes of inheritance

Autosomal dominant inheritance (OMIM, Orphanet)

Autosomal dominant inheritance (HPO)

Source: GTR (NCBI/NIH)8

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It doesn't always run in the family - many children with achondroplasia have parents of normal height.

Source: NHS Choices UK9

Inheritance of Achondroplasia

Genetic and familial features of the condition may include:10 Genetics of Achondroplasia:



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References

  1. Source: NHGRI (NIH): genome.gov/ 19517823/ learning-about-achondroplasia/ 
  2. ibid.
  3. Source: NCBI, Genes and Disease (NCBI/NIH): ncbi.nlm.nih.gov/ books/ NBK22217/ 
  4. Source: GHR (NLM/NIH): ghr.nlm.nih.gov/ condition/ achondroplasia
  5. ibid.
  6. ibid.
  7. Source: GARD (NIH): rarediseases.info.nih.gov/ diseases/ 8173/ achondroplasia
  8. Source: GTR (NCBI/NIH): ncbi.nlm.nih.gov/ gtr/ conditions/ C0001080/ 
  9. Source: NHS Choices UK: nhs.uk/ conditions/ Restricted-growth/ 
  10. Source: Human Phenotype Ontology

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Note: This site is for informational purposes only and is not medical advice. See your doctor or other qualified medical professional for all your medical needs.