Achondroplasia is a skeletal dysplasia, also identified as a rare bone disease.
To start, Rare disease is a concept that identifies a condition or a syndrome or a disorder that is very uncommon, affecting less that 1 person in 2000, in the european designation.
One rare disease may affect only a few patients in Europe or near to 250,000. Depends on the rarity of the condition. In Europe there are more than 30 million people affected by one rare disease of over near 8000 rare diseases that exist.
80% of rare diseases have identified genetic origins whilst others are the result of infections (bacterial or viral), allergies and environmental causes or are degenerative and proliferative.
50% of rare diseases affect children.
Achondroplasia is the most common form of chondrodysplasia (Chondro-cartilage / dysplasia-abnormal development) and occurs due to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, encoding a transmembrane receptor that is important in regulating linear bone growth, among other functions.
Mutation: is a permanent alteration in the DNA, in a specific point of a gene or in more than one. Can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely.
- Rhizomelia – disproportion of the length of the proximal limb.
- Exaggerated lumbar lordosis – Excessive curvature of the lower back
- Brachydactyly– (Brachys- short / dactyly- fingers) The shortness of the fingers is relative to the length of other long bones and other parts of the body.
- Macrocephaly and frontal bossing – (macro-big/cephalus-head) Is an unusually large head with a prominent forehead
- Midface hypoplasia – (Hypo- less/reduced. Plasia- growth) The images below showing a normal profile at 28 weeks and a profile at 30 weeks with midface hypoplasia with frontal bossing in a fetus with achondroplasia.
- Thoracolumbar kyphosis – (Kyphos- hump) is first noticed in infancy in children with achondroplasia and is due to mechanical factors, specifically the general muscular hypotonia (Hypo-less/tonus- is the continuous and passive partial contraction of the muscles. It helps to maintain posture)
- Genu varus – Is a physical deformity marked by outward bowing of the lower leg in relation to the thighbow legs. Bow legs
Estimated incidence is at about 1/25,000 live births worldwide.
Characteristic clinical features are visible at birth.
Achievement of gross motor skills is slower than typical due to short limbs, short neck, and large head, in addition to hypotonia.
Midface hypoplasia in combination with adenoid and tonsil hypertrophy can lead to obstructive sleep apnea. Chronic otitis media can lead to hearing problems. Dental crowding is common. Thoracolumbar kyphosis is very common in infancy. Most joints can be hyperextensible and hands are broad, short and trident shaped.
Cord compression at the level of the foramen magnum can be encountered in infancy and early childhood causing central apnea, developmental delay, and long-track signs. Genu varum often occurs in childhood. There is also a small risk of hydrocephalus, with raised intracranial venous pressure. Lower lumbar spinal stenosis with accompanying neurological deficits, has an increased frequency in adulthood, as does cardiovascular disease. Obesity is a common issue.
Adults reach a height of 131±5.6 cm (men) and 124±5.9 cm (women). Affected women must deliver by caesarian section due to small pelvis size.
Diagnosis is based on the presence of characteristic clinical and radiological findings. Skeletal X-rays demonstrate rhizomelia, generalized metaphyseal irregularities, narrowing of the interpediculate distance of the lower lumbar vertebrae and an abnormal pelvis with small square iliac wings and narrow sacrosciatic notch. Molecular genetic testing can confirm a diagnosis by the presence of a FGFR3 mutation.
Prenatal diagnosis can occur incidentally during routine prenatal ultrasound examination in the 3rd trimester. In high risk pregnancies, or in those where achondroplasia is suspected after an ultrasound, fetal DNA can be tested for the FGFR3 mutation to confirm diagnosis. Pre-implantation genetic diagnosis is possible in specialized laboratories.
Inheritance is autosomal dominant so genetic counseling is warranted. If one parent has achondroplasia there is a 50% chance of passing it on to offspring. In 80% of cases, it is due to a de novo mutation in children with parents of average stature. Homozygous achondroplasia is a lethal condition.
Management is multidisciplinary and anticipatory care is essential. Infants may require surgical decompression of the foramen magnum, and/or shunting for hydrocephalus. Some may choose controversial limb lengthening procedures. Treatment of ear infections and serous otitis media, along with assessment of any hearing problems is needed. Speech therapy can be offered if concerns arise. Treatment of obstructed sleep apnea may include adenotonsillectomy, weight loss, and/or continuous positive airway pressure. Surgical correction can re-align bowing of legs. Adult patients may require a lumbar laminectomy to treat spinal stenosis. Weight gain should be monitored in childhood to avoid later complications. Activities which lead to a risk of injury to the craniocervical junction should be avoided. Social and psychological support should be offered.
There is only a slight decrease in life expectancy compared to the general population, potentially due to cardiovascular disease.