Brief overview
- Symptoms: reduced growth in the length of the upper arm and thigh bones, enlarged skull, deformation of the spine
- Causes: Premature ossification of the cartilage cells formed in the growth plates, as a result of which length growth comes to a standstill
- Diagnosis: suspected diagnosis based on typical symptoms, confirmed by genetic analysis
- Treatment: only necessary if symptoms occur, the length of arms and legs can be adjusted surgically under certain circumstances
- Prognosis: impaired bone growth can lead to health problems such as pain, poor posture and frequent infections, life expectancy is normal.
What is achondroplasia?
Achondroplasia, also known as chondrodysplasia or chondrodystrophy, is the most common cause of short stature (dwarfism). Overall, however, the disease is very rare: Around one in 25,000 newborns worldwide is affected. The genetic mutation can either occur spontaneously or be inherited from an affected parent. Even before birth, doctors can detect the first signs of the disease in an ultrasound scan of the unborn child.
Achondroplasia: symptoms
In achondroplasia, the upper arms and thighs in particular are shortened, whereas the trunk is not affected. As only some bones grow to a limited extent, the body proportions change (disproportionate short stature). Some of the typical characteristics of achondroplasia can be seen in the baby immediately after birth or even during ultrasound examinations during pregnancy. These include
- a long, narrow torso
- an enlarged skull with a high forehead
- a flat, sunken nasal root
- broad, short hands with short fingers
- an enlarged distance between the middle finger and ring finger (trident hand)
The most striking symptom of people with achondroplasia is their short stature. Affected women are on average between 118 and 130 cm tall, men between 125 and 137 cm tall. The spine also does not grow evenly in those affected. As a result, the thoracic spine curves more forwards (kyphosis) and the lumbar spine more backwards (hollow back). As a result, those affected have a bulging abdomen and a waddling gait.
In the lower leg, the inner tibia is shortened in relation to the outer fibula. As a result, the legs are bent outwards (“bow legs”, varus position). Many sufferers have pain in the back and in the knee and hip joints due to the altered anatomical conditions. In addition, middle ear and sinus infections develop more frequently.
In addition, there is often low blood pressure (hypotension) and an overall reduction in muscle tension (muscle tone). Infants with achondroplasia often have pauses in breathing (apnea). In infants, motor development is delayed. However, neither intelligence nor life expectancy are altered in people with achondroplasia.
Achondroplasia: causes
The term achondroplasia comes from the Greek and means “lack of cartilage formation”. In achondroplasia, a site in the growth gene FGFR-3 (fibroblastic growth factor receptor) is abnormally altered (point mutation). The gene contains the building instructions for the so-called fibroblast growth factor receptor, a protein that receives and transmits growth signals. Due to the mutation, the receptor is permanently active – i.e. even without corresponding growth signals – as a result of which the cartilage cells in the growth plate receive incorrect growth signals.
In around 80 percent of people with achondroplasia, the cause of the disease is a newly (spontaneously) occurring point mutation in the germ cells of the parents. The parents themselves are therefore healthy. The risk of such a new mutation increases as the age of the father increases. It is very unlikely (less than one percent) that healthy parents will have several children with achondroplasia.
In the remaining 20 percent, the FGFR-3 gene is already altered in one or both parents. The affected parent is 50 percent likely to pass on the abnormal gene to their child. If both mother and father have achondroplasia, the chance of a healthy child is 25 percent and 50 percent for a child who also has achondroplasia. Children who inherit the diseased gene from both parents (25 percent) are not viable.
Achondroplasia: examinations and diagnosis
Achondroplasia is diagnosed by the doctor in childhood on the basis of the characteristic features. They can often detect a shortened thigh as early as the 24th week of pregnancy during an ultrasound scan. Babies are on average 47 cm tall at birth on the due date, i.e. slightly smaller than healthy children.
If achondroplasia is suspected, regular MRI scans of the head and neck should be carried out during childhood. This allows the doctor to determine, for example, whether the cerebrospinal fluid channel between the head and neck is sufficiently wide or whether an operation is necessary.
He also records body growth and checks the position of the legs and spine. If symptoms such as pain, signs of paralysis or frequent inflammation occur, it is advisable to consult specialists such as orthopaedists, neurologists or ear, nose and throat specialists.
For parents whose unborn child is suspected of having achondroplasia, a specialist in human genetics is the right person to contact. This also applies to parents who already have a child with the disease. A human geneticist is a specialist in genetic diseases. They can diagnose achondroplasia and initiate the necessary preventive examinations. They can also advise parents on family planning.
Achondroplasia: Treatment
Drug therapy
The active substance approved by the European Medicines Agency (EMA) in 2021 inhibits the growth factor receptor FGFR-3, which is permanently activated in achondroplasia and prevents normal bone growth. Inhibiting FGFR-3 improves the symptoms of the disease. In the approval study, affected children between the ages of five and 18 grew an average of 1.5 cm more per year than untreated children.
Leg lengthening
If there is a significant leg deformity, this can be corrected by surgery. The method used is called callus distraction. The doctor cuts through the bone and then fixes it with the help of a holding system (external fixator) attached through the skin from the outside. Alternatively, the doctor inserts a special nail, known as an extension nail, into the bone marrow cavity.
With all devices, the separated bone parts are slowly and continuously moved away from each other after the procedure (distraction). This causes new bone (callus) to form between the two bone ends. It takes about a month for one centimeter of structured, solid bone to form. Nerves and blood vessels grow during this procedure. Muscles and tendons, on the other hand, can only lengthen to a limited extent.
Spinal column stabilization
If movement restrictions, paralysis or severe pain occur due to spinal canal stenosis, the trapped nerves need to be relieved. To do this, the doctor can surgically stabilize the spine with plates and screws. This type of operation is usually accompanied by movement restrictions. If the nerve fluid cannot drain sufficiently from the head, it is possible to drain it into the abdominal cavity via an artificially created channel. This also requires a surgical procedure.
Operations in the ear, nose and throat area
If achondroplasia causes repeated middle ear or paranasal sinus infections, it is possible to surgically improve the ventilation of both organs. Such operations are also performed on healthy people with repeated middle ear and sinus infections.
Achondroplasia: course of the disease and prognosis
The altered bone growth can lead to health restrictions such as frequent colds, poor posture, pain, hydrocephalus and paralysis. They can be detected and treated at an early stage with regular check-ups. Parents can pass the hereditary disease on to their children. Genetic counseling is therefore recommended for family planning. People with achondroplasia have normal intelligence and normal life expectancy.