Disease Site

Achondroplasia is a disorder of bone growth that causes the most common form of dwarfism. It is characterised by a trunk of normal length, short broad limbs, an enlarged skull, small face and flattened nose bridge. Intelligence and reproductive function are unaffected.

Incidence

Achondroplasia affects about 1 in every 40,000 births worldwide. There does not appear to be any racial predisposition. Males and females are affected equally.

Predisposing Factors

Achondroplasia may be inherited as an autosomal dominant trait. However, in the majority of cases, approximately 80% arise from spontaneous mutations – both parents are of normal stature and have no family history of dwarfism. Of these, there is an association with increased paternal age.

Natural History

Achondroplasia is characterised by delayed achievement of gross motor milestones such as head control, independent sitting and ambulation. Recurrent episodes of otitis media are common in children under 5 years due to temporal bone abnormalities. The likelihood of respiratory complications is increased due to reduced thoracic capacity and deformities such as pectus excavatum.

In the first few years of life, there is risk of compression of the brain stem as the foramen magnum does not enlarge accordingly. This may result in respiratory failure, quadraparesis and sudden death. Neurologic disturbances are common. Spinal stenosis is characterised by symptoms of lower back pain, leg pain, paraesthia, and loss of bladder/bowel function.

Over half of patients experience symptoms of nerve root compression or cauda equina syndrome. Facial pain due to trigeminal neuralgia, or ankle pain due to peroneal nerve irritation may occur due to abnormal nerve stretching caused by anatomical variations.

Clinical History

Whilst the disorder usually occurs as a result of a spontaneous mutation in the associated gene, it may still be wise to test parents for the presence of the dominant gene and obtain a family history of the disorder.

Clinical Examination

Short stature for both sexes. For males, average height is 131 cm, for females 124 cm.

  • Sitting height is normal;
  • Average trunk length;
  • Short arms and legs, with disproportionately short upper arm/thigh;
  • Shortened fingers;
  • Increased head size, with prominent forehead;
  • Marked curvature of the spine (kyphosis and lordosis);
  • Waddling gait.

General Investigation

Imaging

Characteristic radiological features:

  • Lateral skull shows frontal prominence, reduced foramen magnum size;
  • AP lumbar spine shows reduced distance between pedicles from L1-5;
  • Lateral spine shows shortening of pedicles and ‘scalloping’ of the vertebral bodies. A thoracolumbar kyphosis may be noted;
  • Short broad pelvis with squared ilium;
  • Metaphyseal flaring of long bones;
  • CT scan to assess size of foramen magnum, thoracic cavity and spinal canal;
  • MRI is valuable for detecting cervical stenosis, medullary compression and other abnormalities.

Prognosis

Homozygotes only survive a few weeks or months after birth due to thoracic cage constriction. Heterozygotes have a normal life span and intelligence. They are usually independent in their daily life activities and live fulfilling lives. However, they are at increased risk of developing neurologic, respiratory and cardiac complications which are the major causes of death.

Treatment Overview

Medical

There has been much interest in the use of recombinant human growth hormone (somatropin) to increase the height of patients with achondroplasia. A young age at commencement of therapy is recommended, however, no long term studies have been completed.

Surgical

This includes laminectomies for spinal stenosis, spinal fusion for severe thoracolumbar kyphosis and tibiofibular osteotomy for correction of genu varum. Foramen magnum decompression is sometimes performed. Management should be shared with relevant specialties including genetics, orthodontics, speech therapy, respiratory, paediatrics and dietetics.

References

  1. Bassett GS. The osteochondrodysplasias. In: Morrissy RT, Weinstein SL (eds). Lovell and Winter’s Pediatric Orthopaedics (4th edition). Philadelphia: Lippincott Williams and Wilkins; 1996: pp 203-54. [Book]
  2. John Hopkins Department of Orthopaedic Surgery.
  3. Kumar P, Clark M (eds). Clinical Medicine (5th edition). Edinburgh: WB Saunders Company; 2002: p 586. [Book]
  4. MEDLINE Plus [online]. Achondroplasia [cited 19 September 2018]. Available from: URL link
  5. Parikh S, Batra P. Achondroplasia. eMedicine; 2002.
  6. Cotran RS, Kumar V, Collins T, Robbins SL. Robbins Pathologic Basis of Disease (6th edition). Philadelphia: WB Saunders Company; 1999. [Book]

Drugs/Products Used in the Treatment of This Disease: