What is Achondroplasia?
Achondroplasia is a rare genetic disorder of bone growth that prevents cartilage (especially in the long bones of arms and legs) from turning into bone. It is characterized by dwarfism, restricted freedom of movement at the elbows, large head size (macrocephaly), small fingers, and normal intelligence.
Achondroplasia is also known as ACH, achondroplastic dwarfism, dwarf, or achondroplasty.
The word “achondroplasia” literally means “without cartilage formation”. Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, with achondroplasia, the problem is not in forming cartilage, but in turning it into bone (a process called ossification), particularly in the long bones of the arms and legs.
Achondroplasia is similar to another skeletal disorder called hypochondroplasia, but the features of achondroplasia tend to be more serious.
The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult women is 124 centimeters (4 feet, 1 inch). According to The Children’s Hospital of Philadelphia (CHOP). It is rare for an adult with achondroplasia to reach a height of 5 feet.
Causes of Achondroplasia
During early fetal development, much of the human skeleton is made up of cartilage. Usually, most of the cartilage eventually turns into bone. In people with achondroplasia, much of their cartilage does not convert to the bone. This is caused by a gene change (mutation) in the FGFR3 gene.
FGFR3 is the only known gene associated with achondroplasia. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3, which is involved in converting cartilage into bone.
The bones of embryos are largely made of cartilage and are therefore soft. Ossification uses calcium to create hard, strong bones as the child grows. When growth factors bind to the FGFR3 protein, it is activated (switched on) and FGFR3 can regulate the ossification process.
Mutations in the FGFR3 gene lead to a change in the FGFR3 protein, especially the amino acid? Glycine is replaced by the amino acid arginine.
This causes the FGFR3 protein to be missing or damaged so that it cannot interact with external growth factors and therefore cannot control ossification. This creates problems during bone development where cartilage does not turn into bone.
How Is Achondroplasia Inherited?
In more than 80 percent of cases, achondroplasia is not inherited. If achondroplasia is inherited, it is inherited as an autosomal dominant trait. Over 80 percent of people who have inherited achondroplasia have parents of normal stature and are born with achondroplasia due to a new (de novo) genetic change (mutation).
About 80 percent of people with achondroplasia have parents of average height. These cases result from new mutations in the FGFR3 gene. In the remaining cases, people with achondroplasia inherited an altered FGFR3 gene from one or two affected parents.
The mutation follows an autosomal dominant inheritance pattern. This means that only one parent needs to pass on a defective FGFR3 gene for a child to suffer from achondroplasia. If either parent has this condition, the child has a 50 percent chance of having it.
If both parents have the condition, the child has:
- a 25 percent chance of normal stature
- a 50 percent chance of having one defective gene that causes achondroplasia
- a 25 percent chance of inheriting two defective (altered) genes, which would lead to a fatal form of achondroplasia known as homozygous achondroplasia.
People who inherit two altered copies of this gene typically have a severe form of achondroplasia, which causes extreme shortening of the bones and an underdeveloped chest. These people are usually stillborn or die of respiratory failure shortly after birth.
If your family has a history of achondroplasia, consider genetic testing before pregnancy so that you fully understand the health risks of your future child.
Frequency Of Achondroplasia
Achondroplasia seems to affect men and women equally. This disorder begins in the developing fetus and is one of the most common forms of skeletal dysplasia that causes dwarfism. The estimated incidence of achondroplasia was between one in 15,000 and one in 40,000 births.
What Are The Symptoms Of Achondroplasia?
The following are the most common symptoms of achondroplasia, but each child may experience symptoms differently:
The following are the most common symptoms of achondroplasia, but each child may have different symptoms:
- shortened arms and legs, with the upper arms and thighs more shortened than the forearms and lower legs.
- Large head size with protruding forehead and flattened nasal bridge.
- crowded or misaligned teeth.
- Curved lower spine – a condition also known as lordosis (or backswing) that can lead to kyphosis or the development of a small hump near the shoulders that usually goes away after the child starts walking.
- small vertebral canals (back bones) – can lead to compression of the spinal cord in adolescence (occasionally, children with achondroplasia may die suddenly in infancy or early childhood from compression of the upper end of the spinal cord that affects breathing.)
- Bent lower legs
- Flat feet that are short and wide
- additional distance between middle and ring finger (also called trident hand)
- poor muscle tone and loose joints
- frequent otitis media, which can lead to hearing loss
- normal intelligence
- Delayed developmental milestones such as walking (which can occur between 18 and 24 months)