achondroplasia

Achondroplasia: description

Achondroplasia is the most common cause of the so-called short stature (dwarfism), but very rarely. The figures in the literature vary: Of 100,000 people, between three and ten suffer from achondroplasia. The gene change can either occur spontaneously or be inherited from a diseased parent. Already before the birth one can recognize first signs of the illness in an ultrasound examination of the unborn child.

Genetic testing will certainly detect the disease. Apart from the visible physical changes, achondroplasia does not require any physical discomfort. Due to the altered bone growth, symptoms that require treatment may develop over the course of life.

Achondroplasia: symptoms

The most striking symptom in people with achondroplasia is a small body size. Affected women are on average between 112 and 138 cm tall, men between 118 and 143 cm. Especially the upper arms and thighs are shortened. The trunk, however, is usually unchanged, so people with achondroplasia reach an almost normal sitting height. Because only a few bones grow restricted, the body proportions (disproportionately short stature) change. The following changes can occur:

• big head (water head or hydrocephalus)
• high forehead
• narrow face
• small nose bone with sunken nose root
• short neck
• short upper arms without full extension in the elbow
• short fingers
• Trident hand: increased distance between ring and small finger
• short thighs
• “O-legs” (varus position in the knee)
• Hollow back (hyperlordosis of the lumbar spine)
• skinfold

These visible growth changes may result in further symptoms of achondroplasia. Affected persons often have a bulging belly, a waddle (short steps with wavering upper body), back pain, knee and hip joint pain and often middle ear and sinusitis (due to changes in ear, nose and throat anatomy). In severely impaired spine even paralysis can occur, which arise due to pressure on the nerves in the spinal canal (spinal canal).

In addition, there is often low blood pressure (hypotension) and an overall reduced muscle tension (muscle tone). Infants with achondroplasia have more frequent respiratory breaks (apnea). In infants, motor development is delayed. Neither intelligence nor life expectancy are altered in people with achondroplasia.

Achondroplasia: causes and risk factors

The term achondroplasia comes from the Greek and means translated “missing cartilage formation”. In achondroplasia, a site in the growth gene FGFR-3 (fibroblastic growth factor receptor) is pathologically altered (point mutation). As a result, cartilage cells receive false growth signals. Normally, cartilage is first formed in the growth zone and then rebuilt into bone.

In people with achondroplasia, the cartilage cells in some bones ossify too early. As a result, the affected bones grow slower and stay shorter. Especially the upper arm and thigh are affected. In the lower leg, the (internal) tibia (tibia) compared to the (external) fibula (fibula) is shortened. The legs are bent outwards (“O-legs”, varus position).

The spine also does not grow evenly. As a result, the thoracic spine is bent more towards the front (thoracolumbar kyphosis) and the lumbar spine more towards the back (hollow back, lumbosacral hyperlordosis). The spinal canal is narrowed (spinal canal stenosis) and can affect nerves. Since the passage from the brain to the spinal cord is often narrowed, the cerebrospinal fluid (CSF) can not circulate as usual between the head and the spine. It then accumulates in the head and can lead to a large hydrocephalus.

The disproportionate head growth is often associated with a small auditory canal and large palatine tonsils (adenoids). Middle ear and paranasal sinuses are poorly ventilated and more susceptible to infection. Achondroplasia: inheritance

In about 80 percent of people with achondroplasia, the disease is caused by a new (spontaneous) point mutation in the germ cells of the parents. The parents themselves are healthy. The growth gene FGFR-3 only changes at one site compared to a healthy gene.

This defect of DNA (deoxyribonucleic acid) can occur spontaneously in the maternal or paternal genetic material. With increasing paternal age increases the risk of such a new mutation. It is very unlikely (below one percent) that healthy parents get multiple children with achondroplasia.

In the remaining 20 percent of cases of achondroplasia an autosomal dominant genetic pattern is present. An affected person passes on the pathologically altered gene to his child with a probability of 50 percent. With only one parent, four children are statistically healthy and one also has achondroplasia. If both mother and father have achondroplasia, the chance for a healthy child is 25 percent and for a child also suffering from achondroplasia 50 percent. Children who inherit the diseased gene from both parents (25 percent) are not viable.

Achondroplasia: examinations and diagnosis

The right contact for achondroplasia is a specialist in human genetics. He is a specialist in genetic diseases, can diagnose achondroplasia, initiate necessary check-ups and refer you to other specialists for complaints. He can also advise you on family planning. Some paediatricians and gynecologists have also specialized in genetic diseases. The doctor might ask you the following questions:

• Have people in your family contracted achondroplasia?
• Have people in your partner’s family contracted achondroplasia?
• Do you already have children? Are these healthy?
• Is there a (further) desire for children?
• Do you suffer from pain?
• Have you already had surgery on the bones?
• Do you have more and more colds or infections of the ears and sinuses?

The diagnosis of achondroplasia is made as early as childhood. Often you can already see a shortened thigh in the pregnancy ultrasound of the 24th week of pregnancy. Infants are on average 47 cm tall at birth at the calculated date, which is slightly smaller than healthy children. You can certainly prove the disease only with a genetic test. For this the DNA from a blood sample is examined. It may take between two and six weeks for the result to be proven and for a mutation to be detected.

If the suspicion of achondroplasia is confirmed, MRI of the head and neck should be performed regularly in childhood. This allows you to determine whether the brainwave canal between head and neck is sufficiently wide or surgery is necessary. In addition, the body growth is recorded and the leg and spine position checked. Symptoms such as pain or frequent inflammation, are affected by an orthopedic or ear, nose and throat doctor.

Achondroplasia: treatment

Achondroplasia does not necessarily have to be treated. If there are no symptoms, regular check-ups are sufficient. The height can only be changed by surgery. Growth hormone preparations improve growth only insignificantly and not reliably. Further therapies are only carried out if symptoms are present.

leg extension

Surgical leg lengthening should be considered carefully as major complications can occur. If there is a significant leg malposition, this can be corrected by surgery. The method used is callus distraction. The bone is severed in an operation and fixed. Depending on the leg position, an externally attached annular metal frame (ring fixator) or a one-sided (unilateral) fixator can be connected to the bone. In addition, a nail can be inserted into the bone marrow cavity (intramedullary extension nail).

In all devices, the diverged bone parts are slowly moved away from each other after a week (distraction). New bone (callus) forms between the two ends of the bone (callus, up to one centimeter of structured, solid bone passes by for about a month) Nerves and blood vessels grow with this procedure, but muscles and tendons can only extend to a limited extent This treatment would last more than two years and is therefore ethically acceptable at most in adulthood.

spinal stabilization

If movement restrictions, paralysis or severe pain occur due to spinal canal stenosis, trapped nerves must be relieved again. For this, the spine can be stabilized with plates and screws. Mostly, such an operation is associated with movement restrictions. If the nerve water from the head can not drain sufficiently, it can be discharged via an artificially created channel into the abdominal cavity. This also requires surgery.

Operations in the ear, nose and throat area

Common middle ear or paranasal sinus infections are treated as in people without achondroplasia. If they occur repeatedly, the ventilation of the two organs can be surgically improved. These operations are performed just as in healthy people with recurrent middle ear and sinusitis.

Achondroplasia: disease course and prognosis

Altered bone growth can lead to health problems such as frequent colds, poor posture, pain, hydrocephalus and paralysis. If these problems are detected early in check-ups, they can be treated well. The hereditary disease can be passed on to children, therefore, genetic counseling is recommended for family planning. People with achondroplasia have a normal intelligence and normal life expectancy.