Achondroplasia is an autosomal dominant disorder of the fibroblast growth factor receptor 3 gene (FGFR3 gene) which is present on chromosome 4. It is the most common form of short-limb dwarfism and the most common form of skeletal dysplasia. Skeletal dysplasia is a category of genetic disorders that lead to abnormal bone growth.
Pathophysiology
Achondroplasia occurs due to mutations of the FGFR3 gene on chromosome 4. The mutations can be inherited in an autosomal dominant pattern. Around 80% of cases are actually due to a de novo variant and not an inherited pattern. This de novo variant is associated with paternal age >35 years.
It is a heterozygous condition as a homozygous pattern is fatal in the neonatal period and as such incompatible with life.
The FGFR3 gene is responsible for regulation of bone growth by inhibiting endochondrial ossification of hyaline cartilage. By inhibiting this process the chondrocytes are able to proliferate and the long bones are able to grow before ossifying later on in life. This process usually occurs up until 25 years of age. With mutation of the FGFR3 gene, there is overactivity of the receptor which leads to further inhibition of chondrocyte proliferation that prevents it from growing and differentiating resulting in impaired matrix synthesis and impaired bone growth.
⚠️ Risk factors
- Parent with achondroplasia
- Advanced paternal age (>35 years old)
😷 Presentation
The evident feature is disproportionate dwarfism or disproportionate short stature (DSS). This is when there is an average trunk size but abnormally short limbs.
- Disproportionate skull
- The skull base grows and fuses via endochondrial ossification. Endochondrial ossification is affected with achondroplasia and this leads to a flattened midface and nasal bridge and a foramen magnum stenosis which can lead to sleep apnoea and sudden respiratory arrest.
- The bones of the cranial vault (the region which the brain occupies) grow and fuse via membranous ossification and this process is unhindered in achondroplasia. This leads to a normal sized vault → frontal bossing.
- Shortened digits - these digits are held in groups of 3 leading to a “trident hand”.
- Bowing of tibias (genu varum)
- Lumbar lordosis
- Average height of 121 cm (varies between 80-150cm)
🔍 Investigations
- Clinical diagnosis based on clinical presentation and X-ray features.
- X-ray findings include:
- Metaphyseal irregularities
- Genu varum
- Rhizomelic shortening - “rhizomelic refers to the hip and shoulder”
- Narrow pelvis with square iliac wings (champagne glass pelvis)
- Narrow spine
🧰 Management
There is no specific management to treat achondroplasia. The life expectancy of the individual is normal and their intellectual capabilities are not affected.
Patients with achondroplasia have their growth monitored using condition-specific centile charts.
Management usually relates to treatment of complications. The MDT is used to support their development and functioning. This may involve:
- Paediatricians
- Specialist nurses
- Physiotherapists
- Dieticians - as excess weight gain is a significant issue for children with achondroplasia.
- Occupational therapists
- Orthopaedic surgeons
- ENT surgeons
- Geneticists
Let’s discuss some of the surgical options that may be performed:
- Leg lengthening surgery - may be offered to add height but it is an extensive surgery that has a long recovery period. It involves tibial osteotomy (cutting of the bone) and adding a distraction (gap) and then using an Ilizarov frame to externally fixate the bones. Over time bone will form between the distraction → lengthening of the bone. It may lead to chronic pain and reduced function.
- Enlargement of the foramen magnum - for cases of severe foramen magnum stenosis.
- Lumbar laminectomy - for spinal stenosis.
🚨 Complications
- Recurrent otitis media - due to craniofacial abnormalities.
- Kyphoscoliosis
- Spinal stenosis
- Obstructive sleep apnoea
- Obesity
- Hydrocephalus and cervical cord compression (due to foramen magnum stenosis)
- Osteoarthritis