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Achondroplasia

  • Achondroplasia is an autosomal dominant condition that affects the skeletal system. It is the most frequent form of disproportionate short stature.
  • Achondroplasia is caused by a mutation in the FGFR3 gene, located on chromosome 4p16.3. Seventy-five per cent of people who have achondroplasia have the condition as a result of a new mutation, in that they did not inherit the condition and are born to parents of average stature.
  • Antenatal ultrasound may detect foreshortened limbs.
  • Prenatal diagnosis to identify the causative mutation is possible in pregnancies where one or both of the parents have achondroplasia.
  • When a child inherits the altered gene from both parents, the condition is severe and is not compatible with life.

Clinical features

  • People with achondroplasia usually have a normal life expectancy, and general health is largely unaffected. Intelligence is within the normal range. Characteristics of the condition include:
    • Short stature with a normal length trunk and shorter arms and legs (average height 131 cm in men and 124 cm in women).
    • A large head with prominent forehead and flattened nasal bridge.
    • Short, broad hands and feet.
    • Flexible joints.
    • Bowing of the lower legs (genu varum).
    • Curvature of the lower spine (lumbar lordosis).
    • Babies with achondroplasia may have delayed motor skills because of the combination of a relatively large head and shortened limbs.
    • Some people with achondroplasia need treatment for hydrocephalus, obstructive sleep apnoea, or middle-ear dysfunction. Neurological complications may appear due to a narrow vertebral canal.

Diagnosis

  • The diagnosis may be suspected in pregnancy when disproportionately short limbs are detected at the mid-term scan.
  • Postnatal diagnosis is based on the presence of typical clinical features, confirmed by specific skeletal changes on X-rays. DNA analysis may identify the alteration in the FGFR3 gene.
  • For couples where one or both have achondroplasia, the genetic status of their baby may be determined by FGFR3 gene molecular analysis on material obtained by chorionic villus sampling or amniocentesis.

Genetic basis

  • About 75% of people with achondroplasia have the condition as the result of a new mutation; the incidence of the condition increases with increasing paternal age.
  • Achondroplasia is inherited as an autosomal dominant condition. Each child of someone who has achondroplasia has a 1 in 2 (50%) chance of inheriting the condition.
  • If both parents have achondroplasia, and a child inherits a copy of the altered gene from both parents, the condition is severe and not compatible with life.
  • The gene for achondroplasia is on the short arm of human chromosome 4.
  • The condition is the result of a mutation in the gene that codes for fibroblast growth factor receptor 3 (FGFR3), which is a key component of cartilage development.
  • Laboratory molecular analysis is relatively straightforward, as the gene alteration is the same in 99% of people with achondroplasia.

Clinical management

  • People who have achondroplasia are likely to benefit from lifelong surveillance and treatment from a specialist clinical team.
  • Children are likely to benefit from care by specialist paediatric services to monitor development, weight, length and head growth using growth charts specific for people with achondroplasia.
  • Specialist ENT and dental intervention may be necessary.
  • Surgical techniques to lengthen lower limbs have been shown to result in increases in height of 30-35cms.
  • Growth hormone treatment may improve short-term growth rate, especially if started early, but it appears that it results in only modest effects.
  • Treatment may be required for craniocervical junction constriction, obstructive sleep apnoea, middle ear dysfunction and spinal stenosis.

 

This information is intended for educational use and was current in August 2013. For clinical management, it is recommended that local guidelines and protocols are used.