Achondroplasia is the most frequent form of short-limb dwarfism.¹ As well as short stature due to shortening of limbs, affected individuals have characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum and trident-like hands.² Incidence increases with paternal age.

Achondroplasia is caused by constitutively activated point-mutated fibroblast growth factor receptor 3 (FGFR3), located at 4p16.3. Epiphyseal growth cartilage fails but with normal bone formation and repair.³

Epidemiology⁴

• Achondroplasia is the most common chondrodysplasia occurring, with the frequency of 1 in 15,000-40,000 worldwide. The prevalence rate has been calculated as 0.5-1.5 cases per 10,000 births and the mutation rate 1.72-5.57 x 10^-5 per gamete per generation.
• The disorder is inherited in an autosomal dominant manner with complete penetrance - but over 80% of cases are spontaneous mutations.¹
• Incidence increases with paternal age.

Presentation⁴

• In the homozygous form the condition is severe and lethal.
• At birth or within first year of life with disparity between large skull, normal length trunk and short arms and legs.
• Fingertips may only come down to the iliac crest.
• Shortness is particularly evident in the proximal segments of limbs.
• Limbs appear very broad with deep creases and trident-like hands.
• Skull shows a bulging vault, small face and a flat nasal bridge or 'scooped out' glabella.
• Spine shows marked lumbar lordosis.

Differential diagnosis

• Hypochondroplasia: less pronounced skeletal disproportion and spinal abnormalities with the skull unaffected.
• Achondroplasia-like dwarfism (distinguish radiologically).
• Spondyloepiphyseal dysplasias: the spine is mainly affected, with the trunk short as well as the limbs.
• Proportionate dwarfism.

Investigations⁴

• The diagnosis is based on the typical clinical and X-ray features. The differentiation from severe hypochondroplasia may be arbitrary.²
• Prenatal diagnosis is by ultrasound. Prenatal diagnosis of homozygous achondroplasia is also available in families at risk and in which the parents are heterozygous for either the 1138A or 1138C allele.
• X-rays show metaphyseal irregularity, flaring in the long bones, and late-appearing irregular epiphyses. The pelvis is narrow in anteroposterior diameter with deep sacroiliac notches and short iliac wings. The spine shows progressive narrowing of the interpedicular distance from top to bottom (reverse of normal).
• Investigation of possible cranial abnormalities and hydrocephalus includes ultrasound, CT and MRI scans. Detailed imaging of the craniocervical junction is particularly important in infants in order to rule out spinal cord compression (see Complications, below).
• Molecular genetic testing is the gold standard. Whilst clinical and X-ray features will identify the majority of patients, this is the only means of differentiating achondroplasia from the other forms of skeletal dysplasias. It is also a helpful investigation prior to considering therapeutic options and genetic counselling¹

Management⁴

• Weight, height and occipitofrontal circumference should be measured in the first year of life.
• Upper to lower segment ratio should be monitored.
• Dental treatment for crowding of teeth.
• Management of frequent middle ear infections. Treatment of obstructive sleep apnoea, e.g. adenotonsillectomy, weight loss and continuous positive airway pressure.
• Measures to control obesity should be initiated as appropriate.
• Growth hormone therapy is still experimental.²
• Anti-inflammatory drugs may be helpful in patients with degenerative joint disease.
• Delivery of pregnant women should be by Caesarean section.
• Surgical intervention includes enlargement of the foramen magnum in cases of severe stenosis, lengthening of the limb bones, tibial osteotomy or epiphysiodesis of the fibular growth plate to correct bowing of the legs, and lumbar laminectomy for spinal stenosis (typically presents in early adulthood).²

Complications⁴

The degree of complications and disability is variable:⁵

• Short arms, limited elbow and hip extension, and knee and leg deformities can cause disabilities in arm function and locomotion.
• Hydrocephalus, a narrow foramen magnum, spinal deformity, and spinal canal stenosis can cause neurological problems (e.g, progressive quadriparesis, pain, ataxia, incontinence) leading to disabilities in locomotion, communication, and learning.⁶
• Skeletal disproportion can lead to early osteoarthritis, problems with childbirth in women, hydrocephalus and paraplegia.
• Narrowing of the spinal canal causes symptoms of spinal stenosis.
• Severe kyphosis may develop in infants; this is due to unsupported sitting before the diagnosis has been made.
• Obesity is common; once the child has reached 75 cm there tends to be a disproportionate increase in weight compared with height.
• Ear, nose and throat abnormalities such as otitis media, upper respiratory tract obstruction, deafness, speech delay, and jaw malocclusion can also lead to disabilities in communication and learning.
• Respiratory complications may include apnoea (including obstructive sleep apnoea) and abnormalities of gas exchange. Children with respiratory dysfunction may be associated with cognitive deficit.

Prognosis⁴

• Life expectancy is normal in the majority of cases.
• Overall cognitive scores are normal but some children may exhibit mild deficits in visual-spatial tasks.
• Final height varies between 80 cm and 150 cm.
• Death in the first year of life can occur due to pressure on the spinal cord, caused by abnormalities at the craniocervical junction. The mortality rate in achondroplastic infants is 2-5%.

Document references

1. Nahar R, Saxena R, Kohli S, et al; Molecular studies of achondroplasia. Indian J Orthop. 2009 Apr;43(2):194-6. [abstract]
2. Online Mendelian Inheritance in Man - OMIM; Achondroplasia
3. Yamanaka Y, Ueda K, Seino Y, et al; Molecular basis for the treatment of achondroplasia. Horm Res. 2003;60 Suppl 3:60-4. [abstract]
4. Defendi G; Achondroplasia. eMedicine.com 2009.
5. Haga N; Management of disabilities associated with achondroplasia. J Orthop Sci. 2004;9(1):103-7. [abstract]
6. Gordon N; The neurological complications of achondroplasia. Brain Dev. 2000 Jan;22(1):3-7. [abstract]

Internet and further reading

• Horton WA, Hall JG, Hecht JT; Achondroplasia. Lancet. 2007 Jul 14;370(9582):162-72. [abstract]
• Achondroplasia: Help and Information from the UK

Acknowledgements