Achondroplasia

Achondroplasia (ACH) is the most common cause of dwarfism and is regarded as one of the oldest known birth problems in humans. Find out more about the condition, including its causes, symptoms, diagnosis, and treatment options.

What is Achondroplasia?

It is a condition that affects growth of the bones and is considered to be the biggest factor for dwarfism. It develops as a sporadic mutation in around 75% cases of dwarfism and is related with advanced paternal age. This is a genetic disorder and may be inherited as an autosomal dominant condition.

It belongs to a group of disorders known as Osteochondrodysplasias or Chondrodystrophies.

Achondroplasia ICD 9 Code

The ICD 9 Code for this disease is 756.4.

Achondroplasia Synonyms

The disorder is also referred to by other names, such as:

Picture 1 – Achondroplasia

• ACH
• Achondroplastic Dwarfism

Achondroplasia Incidence

Although rare, it is also the most common form of short-limbed dwarfism. Around the world, ACH is found to arise in 1 out of every 25,000 individuals. It can be seen to develop in people of all races. It arises in 1 out of 15,000 – 40,000 newborns. This complicated disorder occurs in around 12 in 77,000 in Denmark and approximately 1 in 10,000 births in Latin America.

Achondroplasia Symptoms

The condition results in short stature of its sufferers. Adult males with the disorder have an average height of 131 centimeters (4 feet, 4 inches) while adult females stand at 124 centimeters (4 feet, 1 inch). The structural abnormalities that are characteristic of this disorder include:

• Average-size of trunk
• Short limbs with noticeable shortness in length of thighs and upper arms
• Restricted range of motion at the elbows
• Enlarged head (Macrocephaly)
• Prominent forehead
• Short fingers, with possible divergence of the ring and the middle finger and a three-pronged (trident) appearance of the hand

Fortunately, people suffering from ACH are usually found to be of normal intelligence.

ACH sufferers also experience a number of health problems that are commonly associated with the disorder. These involve problems like:

• Obesity
• Recurrent ear infections
• Apnea (episodic starting or stopping of respiration for short periods)

People suffering from the disorder generally suffer from a prominent curvature in their lower back (Lordosis) and legs. Some sufferers also exhibit an unusual front-to-back spinal curvature (kyphosis) and also experience back pain.

Some of the major characteristics of Achondroplastic dwarfism are evident at birth itself. The problems may include:

• Prominent forehead (Frontal bossing)
• Reduced muscle tone
• Bowed legs
• Spinal stenosis
• Extreme difference in head-to-body size
• Truncated legs and arms (particularly the thigh and upper arm)
• Spine curvatures, known as Lordosis and Kyphosis
• Unusual appearance of hand, with space between the ring finger and long fingers
• Short height (much below the average height of a normal person of similar age and gender)

In ACH sufferers, bones fail to have a normal growth in the absence of proper formation of the cartilages. This makes it impossible for the bones to attain a healthy size similar to that of normal adults. Most individuals with the disorder only stand about 4 feet (1.21 m) tall at adulthood.

Achondroplasia Causes

ACH is autosomal dominant in nature and occurs due to passing on of a defective gene (FGFR3) that has undergone mutation (alteration). It is inherited by a child from his or her parents. Sufferers require only one copy of the mutated gene to develop the disorder. Thus, a parent with this mutated gene (that causes ACH) has a 50% chance of passing it on to each child. If each parent possesses a copy of the defective gene, both of them have a 25% chance of passing on two altered genes to each offspring. Inheriting two genes of the disorder can be life-threatening. Generally, people with two inherited genes for ACH do not survive for long. Newborns with two mutated genes are found to die at birth or immediately afterwards.

An infant has a 50% chance of inheriting ACH with one parent who is a carrier of the disease. In case both parents have a copy of the mutated gene each, the risk of getting the syndrome increases to 75%.

It is noteworthy that a majority of cases of ACH occur as a result of spontaneous mutations. This indicates that two parents without the condition may give birth to an offspring with ACH. This occurs in rare cases where the causative gene may undergo mutation on its own and give rise to the disorder. Studies have revealed the phenomenon to be associated to mutations of the sperm cells of the male parent. These mutations become more common as men grow older.

Although ACH is regarded to be autosomal dominant in nature, there are cases where individuals are found to be born with the disorder even when their parents do not exhibit any external symptoms of dwarfism. This clearly indicates that parents do not have the causative gene as they would have suffered from the disorder had they possessed it.

Achondroplasia and Genetics

As aforesaid, the condition results from mutations in the gene referred to as “FGFR3”. The FGFR3 gene is responsible for providing instructions for the creation of a protein that is involved in the growth and maintenance of brain tissues and bones. Almost all cases of the disorder occur due to two particular mutations in the FGFR3 gene. According to researchers, such mutations lead to hyperactivity of the FGFR3 protein, which affects skeletal development and interferes in bone growth as observed in ACH patients.

Approximately 80 percent of ACH sufferers have parents with average build. In such cases, the condition arises due to fresh mutations in the FGFR3 gene. In the rest of sufferers, patients inherit an altered FGFR3 gene from either or both affected parents.

Achondroplasia Diagnosis

As the causative gene has been identified, ACH can usually be detected in the early stages of pregnancy through genetic testing in utero. Ultrasound examination in the later stages of maternity can further display the unusual characteristics of the disorder, such as abnormal femoral length. As the pregnancy progresses, a mismatch in the length to width ration of the femur is observed. A prenatal ultrasound during pregnancy may exhibit the presence of excessive amniotic fluid around the fetus.

After birth, diagnosis is conducted through physical exam. X-rays exams are also carried out, which help exhibit developmental abnormalities in many of the bones of sufferers. In adults, ACH can be established through observance of abnormal physical features like:

• Short stature
• Bowing of the legs
• Small nose
• Spinal curvature
• Short toes
• Short fingers
• Comparatively large head size

The condition often makes sufferers objects of derision of insensitive people. However, it is usually not a fatal disorder. It can only be life-threatening in those rare cases where an infant inherits the gene from both parents.

After birth, physical examination of ACH babies reveals enhanced front-to-back head size. There may be indications of Hydrocephalus – a condition that is also known as “Water on the brain”. In newborns, X-ray examination of the long bones can reveal abnormalities that are characteristic of the disorder.

Achondroplasia Differential Diagnosis

The symptoms of ACH are similar to those of a number of other ailments. Therefore, the differential diagnosis of the disease aims at distinguishing it from other disorders like:

• Hypochondroplasia
• Spondyloepiphyseal Dysplasia
• Diastrophic Dysplasia
• Homozygous achondroplasia
• Thanatophoric dysplasia
• Proportionate dwarfism

Achondroplasia Treatment

Unfortunately, no specific treatment for this condition exists as of now. Treatment may help manage associated abnormalities, such as Spinal Cord Compression and Spinal Stenosis, when they begin creating problems. In some cases, surgery is required for correction of particular skeletal defects. For instance, osteotomy can be performed in patients with severe bowed legs or knock-knee problems. The surgery is carried out by a pediatric orthopaedic surgeon and involves incision of the bones of the leg. These are allowed to heal in a more proper anatomical poture. Sometimes, a spinal fusion is conducted for permanently joining isolated vertebrae and treating significant spinal kyphosis.

Doctors have recently begun using medications and surgeries to help ACH patients gain height. Such operative techniques involve bone-lengthening surgeries, which include breaking the bones and artificially stimulating their growth to let patients achieve greater stature. Some doctors are also conducting researches with recombinant growth hormone on ACH patients to check whether they have greater effectiveness. However, such studies are still at preliminary stages.

Achondroplasia Risk Factors

The factors that increase the risk of inheriting the condition are:

• Having a parent with achondroplasia
• Having parents who are carriers of a mutated FGFR3 gene
• Having an old father; increased paternal age results in spontaneous mutations

Achondroplasia Complications

Quite a few complications are associated with this disorder. Children with the disorder have a slightly retarded development. They are also susceptible to other problems, such as:

• Ear infections
• Clubbed feet

The narrowing of the spinal canal, also referred to as “spinal stenosis”, is a potentially serious complication of the disorder. This constriction of the spinal canal can compress the upper section of the spinal cord and give rise to physical problems like pain, weakness and tingling sensation in the legs. These can cause problems while walking. Compression of the cord may also cause acute neurological problems. This can be alleviated by a surgical decompression that eases pressure on the cord. A process known as “Laminectomy” helps open the spinal canal at the affected levels.

Fluid accumulation in the brain (hydrocephalus) is another severe complication of ACH, albeit rare. A fluid buildup in the brain of suffering children can result in unusual increase in head size and associated abnormalities of the brain.

Achondroplasia Prognosis

ACH patients rarely grow even 5 feet tall. In adults, final height ranges anywhere from 80 – 150 cm. People with the disorder are fortunately found to have a normal intelligence. Their overall cognitive scores are detected as normal. However, some children may display mild shortfalls in visual-spatial tasks.

Achondroplasia Life Expectancy

Generally, the lifespan of individuals with ACH is the same as those without the gene responsible for its development. In most cases, life expectancy is found to be normal. However, those who inherit a copy of the abnormal gene from both parents frequently survive only for a few months. In such cases, death often occurs in the first year of life due to increased pressure on the spinal cord because of abnormalities at the Craniocervical junction. In achondroplastic infants, the mortality rate tends to vary from 2-5%.

Achondroplasia Prevention

Prospective parents should consider undergoing genetic counseling if one or both of them have this disorder. Counseling by gene specialists can be assistive. However, it is not always possible to avoid the disorder as it is mostly found to develop spontaneously.

Achondroplasia Support Groups

ACH is a lifelong condition and living with the disorder can be difficult for sufferers as well as those close to them. If you have a friend or a family member suffering from ACH, you may get in touch with any of these organizations to receive more information and assistance in tackling the disease.

Picture 2 – Achondroplasia Image

NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675

USA

Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: [email protected]

Website: http://www.niams.nih.gov/

Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: [email protected]

Website: http://www.madisonsfoundation.org

Get in touch with a genetic counselor if you or your partner has a family history of ACH and planning to have children. Knowing about the disorder can help you prevent it from beforehand and also know about managing and treating the condition even if it occurs in your child.

References:

http://ghr.nlm.nih.gov/condition/achondroplasia

http://www.medicinenet.com/achondroplasia/article.htm

http://emedicine.medscape.com/article/1258401-overview

http://children.webmd.com/achondroplasia

http://www.med.nyu.edu/content?ChunkIID=23862#risk