What Is Achondroplasia: Causes – Symptoms and Treatment [Scientific Base]

Achondroplasia is a condition of impaired bone growth caused by a mutation of the protein-producing gene Fibroblast Growth Factor Receptor 3 or FGFR3. The FGFR3 protein is needed by the body in the process of growth and change of cartilage to become harder so that it has an impact on the growth of bones with abnormal shapes and shorter.

Symptoms can be immediately apparent in newborns with achondroplasia, including a large-sized head, short size of arms and limbs, spinal deformity, bulging forehead, as well as muscle weakness. The diagnosis can be done during pregnancy by doing a genetic test.

Complications that can occur can be in the form of recurrent ear infections, posture disorders, dental and oral problems and sleep apnea The treatment of achondroplasia can be in the form of anti-inflammatories, antibiotics and hormonal therapy where this must consult an expert doctor and according to the clinical condition of each patient. Prevention can be done by conducting a genetic test before pregnancy

What is Achondroplasia?

Achondroplasia is a condition of impaired bone growth that also affects the occurrence of dwarfism ^{[1,2,3,4,5,6,7,8]}.

A person with achondroplasia experiences imperfect and disproportionate body growth in which the size of the breastbone is normal, but the legs and arms are shorter.

Patients with achondroplasia have a dwarf body with an average height of 131 cm for older men and 124 cm for older persons women.

Although the physical condition is not proportional, the level of intelligence of achondroplasia sufferers tends to be normal and there are no problems ^[6].

Overview
Achondroplasia is a bone growth disorder that makes the sufferer stunted despite his age of growing up. But the level of intelligence of people with achondroplasia is not at all disturbed in this regard.

Difference Between Achondroplasia and Dwarfism

As previously mentioned, achondroplasia and dwarfism are different but related conditions ^[2,3,4].

This is because achondroplasia as a condition of impaired bone growth is the main cause of the average dwarfism case.

Dwarfism is a type of physical disorder when a growth hormone disorder occurs wherein the levels of this hormone are inadequate causing proportional dwarfism.

Overview
Achondroplasia is a condition that causes dwarfism (a hormonal disorder that causes physical abnormalities due to problematic growth); alternatively, achondroplasia is also known as one of the common forms of dwarfism.

Facts About Achondroplasia

1. Achondroplasia is a rare type of disease and according to Columbia University Medical Center (CUMC) it occurs in only 1 in 25,000 births. ^[1,2].
2. Both men and women have the same risk of developing achondroplasia ^[6].
3. According to the National Human Genome Research Institute (NHGRI), 80% of cases of achondroplasia are not inherited from their parents. ^[2,5].
4. Meanwhile, 20% of achondroplasia cases are inherited disorders because mutations have an autosomal dominant trait ^[2].
5. According to The Children’s Hospital of Philadelphia, the average height of an older person with achondroplasia is about 132 cm or less. ^[2,4,6].
6. Adults with achondroplasia very rarely have a height that reaches 150 cm ^[6].

Causes of Achondroplasia

Genetic mutations are the cause of achondroplasia disorders in which the DNA structure that makes up genes undergoes changes or mutations permanently.

The gene in the body that produces the Fibroblast Growth Factor Receptor 3 or FGFR3 protein is mutated ^{[1,2,3,4,5,6,7,8]}.

In fact, FGFR3 protein is needed by the body in the process of growth and changes in cartilage to become harder.

When the FGFR3 gene mutation occurs, it becomes the main trigger for the protein function to be disturbed so that it cannot work normally.

Changes and growth of cartilage become hard bone eventually experience problems and have an impact on the growth of abnormal shaped and shorter bones.

Mutations in this gene affect primarily the growth of bones in the legs and arms.

However, achondroplasia is not a type of inherited disease because mutations in the FGFR3 gene occur spontaneously.

If both parents have achondroplasia, then there are three possible conditions that can be experienced by the child, namely: ^[1,2,4,6,7]:

• There is a 25% chance that a child will inherit two defective genes, resulting in homozygous achondroplasia, a severe form of achondroplasia.
• 25% chance that the child will not inherit the defective gene so that the body shape is normal.
• There is a 50% chance that a child will inherit a defective gene from one parent that causes him to have achondroplasia.

Meanwhile, in the case of a child with one parent experiencing achondroplasia, there is a 50% chance that the child will also have achondroplasia.

In infants born with the fatal form of achondroplasia (homozygous achondroplasia), the risk of dying several months after birth is very high.

Therefore, it is important for someone to immediately do a genetic test if you have a family member with a history of achondroplasia.

Genetic testing is recommended to be done before planning or carrying out a pregnancy program to understand in detail the health risks of the child after birth.

Overview
- FGFR3 gene mutations are the leading cause of achondroplasia where gene mutations can occur due to hereditary or spontaneous factors. 
- The likelihood of a child developing achondroplasia is greater when one of the two parents has this disorder.

Symptoms of Achondroplasia

Symptoms of achondroplasia can generally be seen from the physical condition of newborns where there are differences from normal babies’ conditions, namely: ^{[1,2,3,5,6,7,8]}:

• You can see the space between the ring finger and the middle finger.
• The teeth are pressed together and do not appear to be out of alignment.
• The head size is larger and looks disproportionate when compared to the body.
• The forehead looks unnaturally protruding.
• Weakness in muscle tone.
• The soles of the feet are wide and tend to be short.
• The spinal canal is narrower than it should be.
• Abnormalities in the shape of the spine, kyphosis (backward curvature of the spine) or lordosis (forward curvature of the bones).
• Fingers, arms and legs are shorter.
• Leg shape O.

In children and older persons with achondroplasia, the following are some of the signs that appear:

• Obesity or overweight
• Difficulty in bending the elbow
• Have spinal deformity getting worse or even happening bone abnormalities new back
• Recurrent infections that occur due to narrowing of the ear canal

The following are health conditions in infants with achondroplasia:

• Hydrocephalus, namely, fluid that accumulates in the brain so that the brain is under pressure.
• Apnea, which is slowing of breathing or even stopping breathing for a short time while sleeping.
• Decreased muscle tone, where this makes the muscles weak and slows the child’s growth and development.

Overview
- The physical condition of the newborn and the physical form/posture as it grows up can indicate whether achondroplasia occurs in it. 
- Large head, short arm and leg size, spinal deformity, bulging forehead, muscle weakness, and dental problems are symptoms of achondroplasia in general.

Achondroplasia examination

Diagnosis is usually made by a doctor during the mother’s pregnancy to check the condition of the fetus.

However, there are also those whose examinations are carried out after the baby is born with more visible symptoms of achondroplasia.

1. Diagnosis During Pregnancy

For the diagnostic method applied by doctors during pregnancy, usually the characteristics of achondroplasia in the fetus can be detected through ultrasound ^{[1,2,4,5,6,7,8]}.

An abnormally large fetal head size or hydrocephalus can be detected during prenatal care.

Genetic testing will generally be recommended when there is a suspicion that the patient has achondroplasia.

Genetic testing is done by taking a sample of amniotic fluid, which is then examined in a laboratory to detect the presence of a defective FGFR3 gene.

2. Diagnosis after the baby is born

In the method of diagnosis after the baby is born, doctors can diagnose through physical characteristics that appear ^{[1,2,3,5,6,7,8]}.

However, to confirm the diagnosis, it is possible for the doctor to perform an X-ray examination, which aims to measure the baby’s bones.

Not only that, blood tests should also be taken so that doctors can find the defective FGFR3 gene in the child’s body.

Review 
Diagnosis of achondroplasia can be done while the baby is still in the womb (through ultrasound) or after the baby is born (through physical examination and X-rays).

Treatment of Achondroplasia

Until now there is no treatment method that is really able to cure achondroplasia.

Treatment provided by medical professionals is primarily aimed at preventing complications and helping to reduce symptoms ^{[1,2,3,4,5,6,7,8]}.

• Anti-Inflammatory Drugs: In patients with achondroplasia with joint disorders, it is important to treat them using anti-inflammatory drugs where their use must be in accordance with a doctor’s prescription.
• Antibiotics: If people with achondroplasia have ear infections, then antibiotics are drugs that will also be prescribed by a doctor.
• Surgical Procedure: In children with achondroplasia, if the conditions allow, the surgical procedure can be taken. The goal of surgery is to treat flexed legs, lengthen the legs, and treat kyphosis.
• Repair of Dental Problems: Irregular teeth are also one of the symptoms of achondroplasia and repair of dental problems can be taken mainly by children who experience these complaints.
• Growth Hormone: Some doctors decide to give the patient growth hormone so that physical growth can be supported. However, the long-term side effects of this method still need careful consideration.

Review 
Depending on the severity of the patient's symptoms, achondroplasia is generally treated with antibiotic medications, anti-inflammatory drugs, growth hormone, dental care, or surgical procedures.

Complications of Achondroplasia

In children with achondroplasia, health problems, complications from achondroplasia can occur.

Not all children with this disorder will experience complications, but the severity and treatment obtained to determine the occurrence of complications.

The following are problems that achondroplasia patients can potentially experience: ^[2,3,8] :

• Dental and Mouth Problems: crooked teeth and too close to each other require treatment from a dentist so that their physical appearance is much better.
• Posture Problems: The average posture of people with achondroplasia is the presence of a lump in the upper back (kyphosis) which generally disappears when the child begins to learn to walk. However, when the child starts to walk, other problems such as lordosis will arise, so physical therapy needs to be taken.
• Recurrent Ear Infections: Ear infections experienced by achondroplasia sufferers do not only occur once or twice, but can occur again and again so that they need special treatment.
• Sleep Apnea: Respiratory disorders (stop breathing for some time) during sleep can occur in infants who have achondroplasia. To treat this complication, a surgical procedure to remove the goiter gland and tonsils need to be done.

Overview.
Achondroplasia can trigger several health complications in sufferers, such as sleep apnea (respiratory disorders / respiratory arrest for some time), ear infections that can occur repeatedly, poor posture due to spinal abnormalities, and poor dental conditions.

Prevention of Achondroplasia

There is no way to prevent achondroplasia, but genetic counseling or consultation can be done, especially for those whose family members have a history of achondroplasia ^[2].

Achondroplasia sufferers also need to consult this with a geneticist before starting a pregnancy program.

Consultation aims to understand in more detail about achondroplasia, which has a high risk of occurring in children if the family has a history of this disorder.

Another prevention effort that can be done is to avoid activities that endanger the condition of the spine.

Overview.
Genetic consultation before having children is important to understand achondroplasia. In addition, avoiding activities that are not good for the spine is also an appropriate prevention.