Achondroplasia

Achondroplasia is the most frequent form of short-limb dwarfism. 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 and genu varum and trident hands.¹ Incidence increases with paternal age. Achondroplasia is caused by constitutively activated point-mutated fibroblast growth factor receptor 3 (located at 4p16.3) - epiphyseal growth cartilage fails but with normal bone formation and repair.²

• Achondroplasia is the most common chondrodysplasia occurring with the frequency of 1 in 15,000.
• The disorder is inherited in an Autosomal dominant manner with complete penetrance - but over 80% of cases are spontaneous mutations.
• Incidence increases with paternal age.

• 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 particularly evident in proximal segments of limbs.
• Limbs appear very broad with deep creases and trident-like hands.
• Skull shows bulging vault, small face and flat nasal bridge or 'scooped out' glabella.
• Spine shows marked lumbar lordosis.

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

• The diagnosis is based on the typical clinical and x-ray features. The differentiation from severe hypochondroplasia may be arbitrary.¹
• Prenatal diagnosis 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 long bones, late-appearing irregular epiphyses. Pelvis is narrow in anteroposterior diameter with deep sacroiliac notches and short iliac wings. Spine shows progressive narrowing of the interpedicular distance from top to bottom (reverse of normal).
• Investigation of possible cranial abnormalities and hydrocephalus includes ultrasound and MRI scans.

• 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).¹
• 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.
• Growth hormone therapy is still experimental.¹
• Delivery of pregnant women by caesarean section.

The degree of complications and disability is variable but may include:³

• 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.⁴
• 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.
• 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.

• Children are of normal intelligence.
• Final height varies between 80cm and 150cm.