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.
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).
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).
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.
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
- The spinal canal is smaller than average in 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.
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.
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.
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.
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.
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).
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.
Females with achondroplasia may require a cesarean section for delivery due to the reduced size and shape of the pelvis.
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.
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.
- Smith's Recognizable Patterns of Human Malformation. Ed. Jones KL. 6th edition. Elsevier Saunders. 2005.
- 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.
- Trotter TL, Hall JG; American Academy of Pediatrics Committee on Genetics. Health supervision for children with achondroplasia. Pediatrics. 2005 Sep;116(3):771-83.
- 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.
- Scott, Charles I. Dwarfism. CIBA Clinical Symposia, 1988. All drawings were done by Dr. Frank Netter and are used with permission from Novartis AG.
- 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.
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If you and your partner are newly pregnant, you may be amazed at the number and variety of prenatal tests available to you. Blood tests, urine tests, monthly medical exams, diet questionnaires, and family history tracking — each helps to assess the health of you and your baby, and to predict any potential health risks.
Unlike your parents, you may also have the option of genetic testing. These tests identify the likelihood of passing certain genetic diseases or disorders (those caused by a defect in the genes — the tiny, DNA-containing units of heredity that determine the characteristics and functioning of the entire body) to your children.
Some of the more familiar genetic disorders are:
- Down syndrome
- cystic fibrosis
- sickle cell disease
- Tay-Sachs disease (a fatal disease affecting the central nervous system)
- spina bifida
If your history suggests that genetic testing would be helpful, you may be referred to a genetic counselor. Or, you might decide to seek out genetic counseling yourself.
But what do genetic counselors do, and how can they help your family?
What Is Genetic Counseling?
Genetic counseling is the process of:
- evaluating family history and medical records
- ordering genetic tests
- evaluating the results of this investigation
- helping parents understand and reach decisions about what to do next
Genetic tests are done by analyzing small samples of blood or body tissues. They determine whether you, your partner, or your baby carry genes for certain inherited disorders.
Genes are made up of DNA molecules, which are the simplest building blocks of heredity. They're grouped together in specific patterns within a person's chromosomes, forming the unique "blueprint" for every physical and biological characteristic of that person.
Humans have 46 chromosomes, arranged in pairs in every living cell of our bodies. When the egg and sperm join at conception, half of each chromosomal pair is inherited from each parent. This newly formed combination of chromosomes then copies itself again and again during fetal growth and development, passing identical genetic information to each new cell in the growing fetus.
Current science suggests that human chromosomes carry from 25,000 to 35,000 genes. An error in just one gene (and in some instances, even the alteration of a single piece of DNA) can sometimes be the cause for a serious medical condition.
Some diseases, such as Huntington's disease (a degenerative nerve disease) and Marfan syndrome (a connective tissue disorder), can be inherited from just one parent. Most disorders, including cystic fibrosis, sickle cell anemia, and Tay-Sachs disease, cannot occur unless both the mother and father pass along the gene.
Other genetic conditions, such as Down syndrome, are usually not inherited. In general, they result from an error (mutation) in the cell division process during conception or fetal development. Still others, such as achondroplasia (the most common form of dwarfism), may either be inherited or the result of a genetic mutation.
Genetic tests don't yield easy-to-understand results. They can reveal the presence, absence, or malformation of genes or chromosomes. Deciphering what these complex tests mean is where a genetic counselor comes in.
About Genetic Counselors
Genetic counselors are professionals who have completed a master's program in medical genetics and counseling skills. They then pass a certification exam administered by the American Board of Genetic Counseling.
Genetic counselors can help identify and interpret the risks of an inherited disorder, explain inheritance patterns, suggest testing, and lay out possible scenarios. (They refer you to a doctor or a laboratory for the actual tests.) They will explain the meaning of the medical science involved, provide support, and address any emotional issues raised by the results of the genetic testing.
Who Should See One?
Most couples planning a pregnancy or who are expecting don't need genetic counseling. About 3% of babies are born with birth defects each year, according to the Centers for Disease Control and Prevention (CDC) — and of the malformations that do occur, the most common are also among the most treatable. Cleft palate and clubfoot, two of the more common birth defects, can be surgically repaired, as can many heart malformations.
The best time to seek genetic counseling is before becoming pregnant, when a counselor can help assess your risk factors. But even after you become pregnant, a meeting with a genetic counselor can still be helpful. For example, sometimes babies have been diagnosed with spina bifida before birth. Recent research suggests that delivering a baby with spina bifida via cesarean section (avoiding the trauma of travel through the birth canal) can minimize damage to the spine — and perhaps reduce the likelihood that the child will need a wheelchair.
Experts recommend that all pregnant women, regardless of age or circumstance, be offered genetic counseling and testing to screen for Down syndrome.
It's especially important to consider genetic counseling if any of the following risk factors apply to you:
- a standard prenatal screening test (such as the alpha fetoprotein test) yields an abnormal result
- an amniocentesis yields an unexpected result (such as a chromosomal defect in the unborn baby)
- either parent or a close relative has an inherited disease or birth defect
- either parent already has children with birth defects or genetic disorders
- the mother-to-be has had two or more miscarriages or babies that died in infancy
- the mother-to-be will be 35 or older when the baby is born. Chances of having a child with Down syndrome increase with the mother's age: a woman has a 1 in 350 chance of conceiving a child with Down syndrome at age 35, a 1 in 110 chance at age 40, and a 1 in 30 chance at age 45.
- you are concerned about genetic defects that occur frequently in certain ethnic or racial groups. For example, couples of African descent are most at risk for having a child with sickle cell anemia; couples of central or eastern European Jewish (Ashekenazi), Cajun, or Irish descent may be carriers of Tay-Sachs disease; and couples of Italian, Greek, or Middle Eastern descent may carry the gene for thalassemia, a red blood cell disorder.
Meeting With a Genetic Counselor
Before you meet with a genetic counselor in person, you'll be asked to gather information about your family history. The counselor will want to know of any relatives with genetic disorders, multiple miscarriages, and early or unexplained deaths. The counselor will also want to look over your medical records, including any ultrasounds, prenatal test results, past pregnancies, and medications you may have taken before or during pregnancy.
If more tests are necessary, the counselor will help you set up those appointments and track the paperwork. When the results come in, the counselor will call you with the news and often will encourage you to come in for a discussion.
The counselor will study your records before meeting with you, so you can make the best use of your time together. During the session, you'll go over any gaps or potential problem areas in your family or medical history. The counselor can help you understand the inheritance patterns of any potential disorders and help assess your chances of having a child with those disorders.
The counselor will distinguish between risks that every pregnancy faces and risks that you personally face. Even if you discover you have a particular problem gene, science can't always predict the severity of the related disease. For instance, a child with cystic fibrosis can have debilitating lung problems or, less commonly, milder respiratory symptoms.
Genetic counselors can help you understand your options and adjust to any uncertainties you face, but you and your family will have to decide what to do next.
If you've learned prior to conception that you and/or your partner are at high risk for having a child with a severe or fatal defect, your options might include:
- pre-implantation diagnosis — when eggs that have been fertilized in vitro (in a laboratory, outside of the womb) are tested for defects at the 8-cell (blastocyst) stage, and only nonaffected blastocysts are implanted in the uterus to establish a pregnancy
- using donor sperm or donor eggs
- taking the risk and having a child
- establishing pregnancy and have specific prenatal testing
If you've received a diagnosis of a severe or fatal defect after conception, your options might include:
- preparing yourself for the challenges you'll face when you have your baby
- fetal surgery to repair the defect before birth (surgery can only be used to treat some defects, such as spina bifida or congenital diaphragmatic hernia, a hole in the diaphragm that can cause severely underdeveloped lungs. Most defects cannot be surgically repaired.)
- ending the pregnancy
For some families, knowing that they'll have an infant with a severe or fatal genetic condition seems too much to bear. Other families are able to adapt to the news — and to the birth — remarkably well.
Genetic counselors can share the experiences they've had with other families in your situation. But they will not suggest a particular course of action. A good genetic counselor understands that what is right for one family may not be right for another.
Genetic counselors can, however, refer you to specialists for further help. For instance, many babies with Down syndrome are born with heart defects. Your counselor might encourage you to meet with a cardiologist to discuss heart surgery, and a neonatologist to discuss the care of a post-operative newborn. Genetic counselors can also refer you to social workers, support groups, or mental health professionals to help you adjust to and prepare for your complex new reality.
Finding a Genetic Counselor
Working with a genetic counselor can be reassuring and informative, especially if you or your partner have known risk factors. Talk to your doctor if you feel you would benefit from genetic counseling. Many doctors have a list of local genetic counselors with whom they work. You can also contact the National Society of Genetic Counselors for more information.