Achondroplasia

Achondroplasia is the most common skeletal dysplasia. Although the exact incidence is not known estimates range from 1 in 15,000 to 1 in 26,000 births. The name literally means failure or lack of cartilage formation. This is not strictly true as cartilage formation does occur in the growth plates of patients with achondroplasia.

 
How Achondroplasia Is Inherited
A child with achondroplasia stands next to his brother.

Achondroplasia is inherited in an autosomal dominant manner, but about 75% of patients with achondroplasia represent new mutations. These new mutations typically arise from the father during sperm formation. Paternal age greater than 35 years has been found to be a risk factor (3,4).

 
Causes of Achondroplasia

Achondroplasia is caused by a mutation in the fibroblast growth factor receptor-3 (FGFR-3) gene (3). Mutations which change the amino acid glycine to arginine at position 380 of the FGFR-3 protein account for >97% of all reported cases of achondroplasia. Normally the FGFR-3 protein functions as "brake" for endochondral bone growth. This typical G380R mutation actually increases the ability of the FGFR-3 protein to slow bone growth and causes the features of achondroplasia. This type of change associated with an increased ability is termed a "gain-of-function" mutation (4).

 
Physical Characteristics

Achondroplasia causes disproportionate short stature. Specifically the limbs are disporportionately small when compared to the trunk. Within the limbs the proximal segment is shorter causing rhizomelia. The average adult height is 52" in men and 49" in women with achondroplasia. Achondroplasts have average intelligence and can lead very rich and productive lives.

Face & Skull:
  • The head circumference may be larger than average.
  • The forehead tends to be prominent. This is termed frontal bossing.
  • The nasal bridge tends to be depressed and the nostrils are upturned.
  • The mid-face is underdeveloped, which is termed maxillary hypoplasia.
  • The foramen magnum, which is the opening in the skull base through which the spinal cord passes, is smaller then average.
An infant with achondroplasia.
Trunk, Chest, & Spine:
  • Thoraco-lumbar kyphosis (TLK) is present in most infants with achondroplasia and is a normal finding. It can be seen represented in the drawing on the right as the prominence in the lower back(5).
  • The TLK is replaced in later childhood by lumbar lordosis or sway back.
  • TLK is thought to be caused by the large head size and poor muscular tone in children who are not yet walking. It improves without treatment in 90% of affected children as they begin to walk.
  • The chest usually is broad and flat. The abdomen and buttocks
    are prominent.
  • The spinal canal is smaller than average in achondroplasia.
An infant with achondroplasia.
Arms & Legs:
  • There is marked ligamentous laxity or loose joints.
  • Despite the loose joints, typically the elbows cannot be fully extended. Less commonly the elbow joint may be out of place. This rarely causes symptoms or loss of function.
  • In infancy and early childhood there is extra space between the 3rd and 4th fingers. This is termed trident hand and disappears spontaneously in later childhood. The drawing below demonstrates the trident (5).
  • The fingers are short and broad giving rise to a stubby appearance.
An x-ray showing the characteristics of achondroplasia.
What are the x-ray characteristics?

Long bones are relatively plump and short. Proximal humerus and femur in infancy have distinctive rectangular or translucent ovals that change by 2 years. Fibulas tend to be longer than tibias.

Spacing between vertebral pedicles decreases rather than increases in the lumbar spine as you move from head to pelvis.

The pelvis is short and broad with wide, non-flaring iliac wings.

 
Making the Diagnosis

For parents of average stature, achondroplasia is sometimes detected by the presence of short limbs on routine prenatal ultrasound performed after 22 weeks. In this situation, the diagnosis can then be confirmed by molecular genetic testing techniques using fetal DNA obtained through amniocentesis. Cesarean section is recommended to deliver babies with achondroplasia, due to their large head size and risk of compression of the brain during the course of a vaginal delivery.

For parents who have achondroplasia or average-statured parents with a previously born child with achondroplasia, amniocentesis or chorionic villus sampling (CVS) can be performed. Using cells obtained by these techniques, DNA testing can then be performed and used to identify homozygous/ heterozygous achondroplasia in the pregnancy.

Most neonates with achondroplasia have average lengths and weights at birth. It is our belief that as many as 15% of children with achondroplasia are not recognized at birth.

In the neonate, infant, older child or adult, the diagnosis of achondroplasia can be made by an experienced physician (usually a clinical geneticist) on the basis of physical and radiologic examinations.

Sequencing of the FGFR-3 gene can be done in all patients, but is only required in unusual cases or cases of doubt.

 
Associated Medical Problems
An x-ray shows an achondroplasia patient’s foramen magnum.

Foramen magnum stenosis: As mentioned above, essentially all children with achondroplasia have a smaller than average foramen magnum. The foramen magnum is the opening through which the spinal cord leads the head to travel down the spinal column. For the vast majority of children this does not present a problem. There are, however approximately 5% or fewer of children with achondroplasia in whom this opening is so small that there is not adequate room for the spinal cord to function properly. These children have what is termed cord compression or compressive myelopathy. This is a very serious medical problem and requires surgical correction. Cord compression due to foramen magnum stenosis has been implicated as the cause of sudden death in a very small proportion of infants with achondroplasia. As with all surgeries performed on Little People, we suggest that care be taken to assure that the physician has experience not only with the procedure, but also performing the procedure on Little People.

Hydrocephalus: Enlargement of head circumference occurs invariably in achondroplasia but does not require treatment unless pressure within the skull (intracranial pressure) increases and interferes with brain function. Standard charts for normal head circumference throughout childhood in achondroplasia are available. If there is any deviation from average, an opinion should be obtained from a neurosurgeon regarding the need for a ventriculo-peritoneal shunt (a tube that drains excess fluid from the brain into the abdominal cavity).

Sleep apneas or Sleep-disordered breathing - 2 types: Sleep disordered breathing is common in achondroplasia with studies demonstrating a very wide range of affected children ranging from 22% - 85%. As many as 20% of children could be severely affected (6). There are 2 types of apneas or disordered breathing and they will be discussed separately.

  • Obstructive apnea - results from the blockage of airflow into and out of the lungs with normal respiratory drive. This is the most common type of apnea in achondroplasia because of the mid-face hypoplasia and hypotonia of the pharyngeal muscles. The end result is a "smaller pipe" for the air to travel through. Many children with achondroplasia adopt an open mouth habitus with the tongue resting on the lower lip to create maximum airway space. This commonly manifests as snoring and causes disturbed sleep. Symptoms can include tiredness, irritability, daytime sleeping, etc.Treatment for obstructive apnea can include weight reduction measures, adenoidectomy-tonsillectomy, continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) at night by nasal mask to keep the airways open. A tracheostomy may be necessary in the most severe cases.
  • Central apnea - results from failure of the respiratory centers in the brain to properly control the process of breathing. In the brainstem, the respiratory centers are in close proximity to the foramen magnum. Therefore, if the foramen magnum is compressing the spinal cord central apnea can result.
 
Musculoskeletal Problems
An x-ray of the legs of a child with achondroplasia.

Genu Varum is more common than genu valgus in achondroplasia. Knock-knees do not need treatment because they do not progress. Bowlegs however can result in symptoms around the knee such as pain and restricted walking ability. Pain around the knee due to bowing should be distinguished from knee pain due to spinal stenosis. A child with achondroplasia and genu varum with associated x-rays is shown below.

Some experts believed that relative overgrowth of the fibula compared to the tibia causes the knee to bend inwards. Therefore, surgery in the past relied on stopping growth in the fibula (epiphyseodesis) or removing a portion of the fibula.

A more recent analysis of this problem has shown that the bend occurs in the lower part of the femur and the upper part of the tibia. In addition, the tibia is twisted along its axis (internal tibial torsion). A few questions need to be answered through long-term studies before treatment can be advocated for genu varum.

  • Does genu varum in achondroplasia affect long-term function?
  • Does it pose an increased risk for knee arthritis in future?
  • How does surgical correction influence natural history?

We are still in the process of addressing these issues and definite answers may not be available immediately. Symptomatic knee arthritis is not a frequent problem in adults with achondroplasia and this is perhaps a reassuring fact for parents. The current recommendation is to undergo surgery only in the presence of bothersome symptoms or if there is severe deformity. Bracing is not advocated because it is difficult to exert enough corrective forces on the bones in the presence of ligamentous laxity.

Spinal stenosis in the lumbar spine is very common in young adults with achondroplasia, though it can occur at any age. The narrow spinal canal found in achondroplasia and the normal size of the spinal cord and cauda equina (nerve bundle at the base of the spine) mean that there is less room for the spinal cord in the achondroplastic spine. In some patients, this narrowing of the vertebral canal results in compression of the nerves. Symptoms include activity-related leg pain that is relieved on squatting down, tingling, pins and needles, or numbness in the feet (paraesthesias), weakness of the legs or rarely, disturbances in control of bladder or bowel function (incontinence). X-rays, CT and MRI scans of the lower spine, confirm the diagnosis. We believe that obesity greatly increases the risk of this problem developing.

A newborn with muskoskeletal problems due to achondroplasia.

Fixed TLK: As mentioned above, most infants with achondroplasia have a TLK and this is normal. In the vast majority of patients, as the child begins to walk, the TLK will spontaneously resolve without treatment. In some children however, the TLK will become fixed or permanent. Prolonged unsupported sitting likely predisposes this to occur. Bracing can be done to treat this problem and, if severe enough, surgery may be required. Typically, when a child is laid on their belly, the thoraco-lumbar region will flatten and indicate that the TLK is flexible. When, however a child is placed face down and a hump in the spine is seen, as pictured below, the TLK is said to be fixed and treatment will be required (5).

 
Problems Elsewhere in the Body
Obesity

Obesity is a common problem in children and adults of all statures, but especially with achondroplasia. Continuous monitoring for obesity is the first step in maintaining an ideal body weight. The problem is compounded if the weight and height charts which were prepared for average-statured children are used for children with achondroplasia. A weight-for-height chart is available specifically for children with achondroplasia and is a useful guide for weight management. Attention to weight issues in childhood is very important as we believe that obesity will significantly increase the risk for spinal problems in young adults or adults with achondroplasia. Equally important to dietary management is attention to physical activities and appropriate exercise.

Pregnancy

Females with achondroplasia may require a cesarean section for delivery due to the reduced size and shape of the pelvis.

ENT

The mid-face is underdeveloped in achondroplasia. This causes several problems in the ear, nose and throat region.

This hypoplasia can lead to overcrowding of the teeth and malocclusion. These problems may also contribute to articulation/speech defects. Sometimes children may have tongue thrust which affects speech clarity.

The Eustachian tube is a normal connection between the middle ear and the upper throat. In achondroplasia, the anatomy of this tube is distorted and persistent fluid in the middle ear can occur. Over the long term, this leads to conductive hearing loss. Hearing should be checked frequently during the growing years. Deafness can also result from poorly formed middle ear bones or due to compression of the brain stem at the foramen magnum. Ear infections are easily treated, and the use of middle ear tubes is common. Because of anatomical differences, we suggest that care be taken to assure that the physician has experience not only with the procedure, but also performing the procedure on Little People.

 
What to Watch For

Given the differences in head size relative to body size in achondroplasia and average children, it is inappropriate to use the average developmental charts to assess an a child with achondroplasia. There are developmental charts for children with achondroplasia and it is critical that these be used.

We often see children with poor head control at several months of age be referred for physical therapy because this is expected for an average-sized child. This should not be done. Infants with achondroplasia receiving physical therapy will not develop head or trunk control at a more rapid rate. Furthermore, the typical exercises done greatly increase the risk for cord compression related to foramen magnum stenosis.

Extreme care should be taken in the position and handling of infants so as to minimize the occurrence of sudden abnormal head and neck motion. The avoidance of soft swings, umbrella strollers and jumpers is recommended. No backpack carriers or front-pack carriers should be used until the child gains complete and total head control.

Properly installed rear-facing car seats with neck support when traveling in a car are important safety measures. This practice should be continued until the child is 20 pounds regardless of age.

Head size should be monitored carefully at least every three months and at most most, monthly in the first few years of life.

We believe that the parents should become comfortable with feeling the anterior fontanelle or soft spot located on top of the infants skull. The fontanelle should be soft and flat. If the fontanelle becomes hard (like a table top) or bulging when the child is at rest, then this should be brought to immediate medical attention.

Diminishing motor milestones, decreased endurance, apnea or any neurological symptoms should be quickly evaluated by an experienced physician.

Speech delay may indicate underlying conductive hearing loss.

Sleep disturbance may indicate cord compression or obstructive sleep apnea and should be brought to an experienced physicians attention immediately.

 
References
  1. Smith's Recognizable Patterns of Human Malformation. Ed. Jones KL. 6th edition. Elsevier Saunders. 2005.
  2. Hunter AG, Bankier A, Rogers JG, Sillence D, Scott CI Jr. Medical complications of achondroplasia: a multicentre patient review. J Med Genet. 1998 Sep;35(9):705-12.
  3. Trotter TL, Hall JG; American Academy of Pediatrics Committee on Genetics. Health supervision for children with achondroplasia. Pediatrics. 2005 Sep;116(3):771-83.
  4. Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, Kaitila I, Loughlin J, Munnich A, Sykes B, Bonaventure J, Francomano CA. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998 Sep;63(3):711-6.
  5. Scott, Charles I. Dwarfism. CIBA Clinical Symposia, 1988. All drawings were done by Dr. Frank Netter and are used with permission from Novartis AG.
  6. Mogayzel PJ Jr, Carroll JL, Loughlin GM, Hurko O, Francomano CA, Marcus CL. Sleep-disordered breathing in children with achondroplasia. J Pediatr. 1998 Apr;132(4):667-71.

Trusted Insights from Nemours' KidsHealth

Dwarfism

There's been a lot of discussion over the years about the proper way to refer to someone with dwarfism. Many people who have the condition prefer the term "little person" or "person of short stature." For some, "dwarf" is acceptable. For most, "midget" definitely is not.

But here's an idea everyone can agree on: Why not simply call a person with dwarfism by his or her name?

Being of short stature is only one of the characteristics that make a little person who he or she is. If you're the parent or loved one of a little person, you know this to be true.

But here are some facts that other people may not realize about dwarfism and those who have it.

Dwarfism:

  • is characterized by short stature. Technically, that means an adult height of 4 feet 10 inches or under, according to the advocacy group Little People of America (LPA).
  • can be caused by any one of more than 300 conditions, most of which are genetic. The most common type, accounting for 70% of all cases of short stature, is called achondroplasia.
  • can and most often does occur in families where both parents are of average height. In fact, 4 out of 5 of children with achondroplasia are born to average-size parents.

Dwarfism isn't:

  • an intellectual disability. A person who has dwarfism is typically of normal intelligence.
  • a disease that requires a "cure." Most people with one of these conditions live long, fulfilling lives.
  • a reason to assume someone is incapable. Little people go to school, go to work, marry, and raise children, just like their average-size peers.

What Causes Short Stature?

More than 300 well-described conditions are known to cause short stature in a child. Most are caused by a spontaneous genetic change (mutation) in the egg or sperm cells prior to conception. Others are caused by genetic changes inherited from one or both parents.

Similarly, depending on the type of condition causing the short stature, it is possible for two average-size parents to have a child with short stature, and is also possible for parents who are little people to have an average-size child.

What prompts a gene to mutate is not yet clearly understood. The change is seemingly random and unpreventable, and can occur in any pregnancy. If parents have some form of dwarfism themselves, the odds are much greater that their children will also be little people. A genetic counselor can help determine the likelihood of passing on the condition in these cases.

Dwarfism has other causes, including metabolic or hormonal disorders in infancy or childhood. Chromosomal abnormalities, pituitary gland disorders (which influence growth and metabolism), absorptive problems (when the body can't absorb nutrients adequately), and kidney disease can all lead to short stature if a child fails to grow at a normal rate.

Types of Short Stature

Most types of dwarfism are known as skeletal dysplasias, which are conditions of abnormal bone growth. They're divided into two types: short-trunk and short-limb dysplasias. People with short-trunk dysplasia have a shortened trunk with more average-sized limbs, whereas those with short-limb dysplasia have an average-sized trunk but shortened arms and legs.

By far, the most common skeletal dysplasia is achondroplasia, a short-limb dysplasia that occurs in about 1 of every 15,000 to 40,000 babies born of all races and ethnicities. It can be caused by a spontaneous mutation in a gene called FGFR3, or a child can inherit a change in this gene from a parent who also has achondroplasia.

People with achondroplasia have a relatively long trunk and shortened upper parts of their arms and legs. They may share other features as well, such as a larger head with a prominent forehead, a flattened bridge of the nose, shortened hands and fingers, and reduced muscle tone. The average adult height for someone with achondroplasia is a little over 4 feet.

Diastrophic dysplasia is a different form of short-limb dwarfism. It occurs in about 1 in 100,000 births, and is also sometimes associated with cleft palate, clubfeet, and ears with a cauliflower-like appearance. People who have this diagnosis tend to have shortened forearms and calves (this is known as mesomelic shortening).

Spondyloepiphyseal dysplasias (SED) refers to a group of various short-trunk skeletal conditions that occurs in about 1 in 95,000 babies. Along with achondroplasia and diastrophic dysplasia, it is one of the most common forms of dwarfism. In some forms, a lack of growth in the trunk area may not become apparent until the child is between 5 and 10 years old; other forms are apparent at birth. Kids with this disorder also might have clubfeet, cleft palate, and a barrel-chested appearance.

In general, dwarfism caused by skeletal dysplasias results in what is known as disproportionate short stature — meaning the limbs and the trunk are not the same proportionally as those of typically-statured people.

Metabolic or hormonal disorders typically cause proportionate dwarfism, meaning a person's arms, legs, and trunk are all shortened but remain in proportion to overall body size.

Diagnosis

Some types of dwarfism can be identified through prenatal testing if a doctor suspects a particular condition and tests for it.

But most cases are not identified until after the child is born. In those instances, the doctor makes a diagnosis based on the child's appearance, failure to grow, and X-rays of the bones. Depending on the type of dwarfism the child has, diagnosis often can be made almost immediately after birth.

Once a diagnosis is made, there is no "treatment" for most of the conditions that lead to short stature. Hormonal or metabolic problems may be treated with hormone injections or special diets to spark a child's growth, but skeletal dysplasias cannot be "cured."

People with these types of dwarfism can, however, get medical care for some of the health complications associated with their short stature.

Some forms of dwarfism also involve issues in other body systems — such as vision or hearing — and require careful monitoring.

Possible Complications and Treatments

Short stature is the one quality all people with dwarfism have in common. After that, each of the many conditions that cause dwarfism has its own set of characteristics and possible complications.

Fortunately, many of these complications are treatable, so that people of short stature can lead healthy, active lives.

For example, a small percentage of babies with achondroplasia may experience hydrocephalus (excess fluid around the brain). They may also have a greater risk of developing apnea — a temporary stop in breathing during sleep — because of abnormally small or misshapen anatomy or, more likely, because of airway obstruction by the adenoids or the tonsils. Occasionally, a part of the brain or spinal cord is compressed. With close monitoring by doctors, however, these potentially serious problems can be detected early and surgically corrected.

As a child with dwarfism grows, other issues may also become apparent, including:

  • delayed development of some motor skills, such as sitting up and walking
  • a greater susceptibility to ear infections and hearing loss
  • breathing problems caused by small chests
  • weight problems
  • curvature of the spine (scoliosis, kyphosis, and/or lordosis)
  • bowed legs
  • trouble with joint flexibility and early arthritis
  • lower back pain or leg numbness
  • crowding of teeth in the jaw

Proper medical care can alleviate many of these problems. For example, surgery often can bring relief from the pain of joints that wear out under the stress of bearing weight differently with limited flexibility.

Surgery also can be used to improve some of the leg, hip, and spine problems people with short stature sometimes face.

Nonsurgical options may help, too — for instance, excessive weight can worsen many orthopedic problems, so a nutritionist might help develop a healthy plan for shedding extra pounds. And doctors or physical therapists can recommend ways to increase physical activity without putting extra stress on the bones and joints.

Helping Your Child

Although types of dwarfism, and their severity and complications, vary from person to person, in general a child's life span is not affected by dwarfism. Although the Americans with Disabilities Act protects the rights of people with dwarfism, many members of the short-statured community don't feel that they have a disability.

You can help your child with dwarfism lead the best life possible by building his or her sense of independence and self-esteem right from the start.

Here are some tips to keep in mind:

  • Treat your child according to his or her age, not size. If you expect a 6-year-old to clean up his or her room, don't make an exception simply because your child is small.
  • Adapt to your child's limitations. Something as simple as a light switch extender can give a short-statured child a sense of independence around the house.
  • Present your child's condition — both to your child and to others — as a difference rather than a hindrance. Your attitude and expectations can have a significant influence on your child's self-esteem.
  • Learn to deal with people's reactions, whether it's simple curiosity or outright ignorance, without anger. Address questions or comments as directly as possible, then take a moment to point out something special about your child. If your child is with you, this approach shows that you notice all the other qualities that make him or her unique. It will also help prepare your child for dealing with these situations when you're not there.
  • If your child is teased at school, don't overlook it. Talk to teachers and administrators to make sure your child is getting the support he or she needs.
  • Encourage your child to find a hobby or activity to enjoy. If sports aren't going to be your child's forte, then maybe music, art, computers, writing, or photography will be.
  • Finally, get involved with support associations like the Little People of America. Getting to know other people with dwarfism — both as peers and mentors — can show your child just how much he or she can achieve.

Reviewed by: Angela L. Duker, MS, CGC
Date reviewed: March 2011