Spondyloepiphyseal Dysplasia

Sphondylos is a Greek term meaning vertebra. Epiphysis refers to the ends of long bones that are adjacent to the joints. Therefore, spondyloepiphyseal dysplasias are disorders that involve both the spine and the ends of long bones. There are many types of spondyloepiphyseal dysplasias (SED), including SED congenital and SED tarda. We will limit our discussion here to SED-congenita (SEDc). As of 1994, approximately 175 well-documented cases of SEDc had
been reported.

How Spondyloepiphyseal Dysplasia Is Inherited

SED-congenita typically has an autosomal dominant pattern of inheritance; however, distinct cases of autosomal recessive inheritance have also been reported (3). Most cases of this dysplasia are due to spontaneous mutations (3). Gonadal mosaicism helps to explain why affected children are oftentimes born to unaffected parents.

Causes of Spondyloepiphyseal Dysplasia

SED-congenita is caused by a mutation of the gene coding for Collagen Type II (COL2A1) found on Chromosome 12 (1). Type II collagen is a structural protein present in the intervertebral discs, cartilage, and the eyeball.

Physical Characteristics
Face and Skull
  • characteristic facial expression of sadness
  • long face, narrow at the level of the eyes
  • mild frontal bossing
  • protruding, wide-set eyes
  • down-turned eyebrows
  • small mouth with cleft palate
  • head appears to rest on chest
Trunk, Chest and Spine:
  • short neck
  • barrel chest with pectus carinatum
  • deep Harrison’s grooves
  • disproportionately small pelvis, set back behind the frontal plane of the shoulders. Patients tend to walk with their head hyperextended and behind their shoulders.
  • short spine
  • marked lumbar lordosis
  • moderate kyphoscoliosis oftentimes occur in late childhood or
    early adulthood.
  • platyspondyly
Arms and Legs:
What Are the X-Ray Characteristics?

The major radiographic features of infancy include a delayed ossification of the skeleton and an absence of ossification centers of pubic bones and knee epiphyses. Ossification of the vertebral bodies of upper cervical spine is absent, and the vertebral bodies of the thoracic and lumbar regions are small and dorsally wedged. The ossification of the sacrum is delayed. The major radiographic features of childhood include flattened and immature vertebral bodies with anterior ossification defects. Hypoplasia of odontoid process of C-2 is characteristic. Ossification of the pelvis is delayed. Femoral head and neck may be absent or incompletely ossified. Coxa vara is common. Epiphyseal and metaphyseal abnormalities of long tubular bones are typical. There is also a delayed appearance of carpal and tarsal ossification centers. The major radiographic features of adulthood include a short spine with moderate kyphoscoliosis and marked lumbar lordosis. Vertebral bodies are flat and irregular. The odontoid process is hypoplastic, with lack of fusion with C-2 body. Femoral trochanters are high-riding. Femoral heads are deformed. Coxa vara is common. The long tubular bones are abnormally short, with flat and deformed epiphyses.

Making the Diagnosis

The diagnosis of SED is made on the basis of clinical features and relevant X-rays. Radiographic features that are particularly characteristic are the biconvex appearance of the ossification center of the vertebral bodies on lateral radiographs of the spine and the several-year delay in the ossification of the iliopubic ramus and epiphyses of the long bones, particularly the femoral heads. Moreover, SED-congenita may be suspected in the prenatal period on the basis of ultrasonography. The gene is known, but testing may be difficult considering its size. Certain mutations of the gene have been associated with different forms of SED.

Musculoskeletal Problems

Individuals with SED have odontoid hypoplasia. If the odontoid is unstable or forms abnormally, it presses on the spinal cord to cause atlantoaxial instability, which is common to many skeletal dysplasias. It is diagnosed on the basis of neck X-rays and MRI scans. The instability causes cervical myelopathy; it manifests even earlier than in patients with Morquio Syndrome. Symptoms, usually of the respiratory type, can be noted in newborns or young infants. Patients will begin to have great difficulty standing independently. Chronic motor weakness will begin to occur in the upper and lower limbs especially, followed by episodes of quadriplegia. Any inability to independently stand and remained balance does suggest myelopathy. Typically, cord compression is treated by surgical fusion of the vertebrae in the upper part of the neck.


Kyphoscoliosis in the thoracolumbar spine is a common feature in SED. It is present is over 50% of patients. Early diagnosis is by means of regular scheduled physical examinations and X-rays. For small curvatures bracing may be attempted, but this is not always successful. If serial x-rays demonstrate a progressive curve, surgical fusion of the spine may be necessary. In one study, the use of a brace was found to be effective for kyphosis when the brace was worn until maturity. Exaggerated lumbosacral lordosis affects nearly every SED-congenita patient. It causes an imbalance of the spine in the sagittal plane. The lordosis is most likely caused by changes in the structure of the vertebral bodies: the pedicles appear abnormally long and the vertical height of the posterior arches appears considerably low. Bracing, around the age of 4 or 5, is a successful attempt to correct the lordosis. However, small children typically do not tolerate the cumbersome brace very well, thereby its practicality is somewhat questionable.

Lower Limbs

Coxa vara is characteristic. The hip is a ball-and-socket joint formed between the pelvis (acetabulum) and the upper part of the femur (head). The head of the femur is connected to the shaft by the neck. Normally the neck makes an angle of 130° with the shaft. In SED, due to abnormal cartilage formation, the neck is unable to withstand the mechanical forces applied to it and the ball gradually bends downwards. Any change in the alignment of the femoral neck weakens the muscles around the hip joint (principally the abductors that stabilize the pelvis during walking) and causes hip joint contractures. Surgery to realign the femoral neck is recommended if symptomatic or if the neck-shaft angle is less than 100°. Genu valgus is more common than genu varus.


Though the medical literature indicates an association between SED and clubfeet, this is not our experience. We find flatfeet (planovalgus) to be much more common in children with SED.


In SED, the part of the bone adjacent to joints is affected. Joint cartilage is also predominantly composed of Type II collagen. Premature osteoarthritis is typical. Joint replacement surgery (hips and knees) may be necessary in early adulthood, but this is variable. The presence of associated joint contractures and bony deformities in SED makes such surgery a technically challenging exercise.

Problems Elsewhere in Body

Type II collagen is present in the eye. SED is therefore associated with myopia (short-sightedness) and retinal detachment. Regular review by an ophthalmologist to exclude retinal tears is recommended.

Respiratory Problems

Abnormal chest development in some forms of SED may cause respiratory insufficiency. Sleep apnea and breathing problems can occur due to compression of the spinal cord in the neck.


Moderate hearing loss may occur, especially for high-pitched sounds. Children with SED are at risk for developing recurrent ear infections due to reduction in the size of the tubes connecting the middle ear cavity to the upper throat (Eustachian tube).

What to Watch for

In SED, regular assessment by a pediatric orthopedic surgeon, conversant in the management of skeletal dysplasias, is essential. Clinical and radiographic assessment should be conducted every 6 months, more frequently if closer supervision of an impending problem is necessary.

Additionally, any change in gait pattern should be taken seriously. This may be associated with tiredness, decrease in walking distance, reduced endurance, or muscle pain. Any alterations in sensation (tingling or numbness in arms and legs) or loss of bowel/ bladder control are indicative of spinal cord irritation or compression.

Changes in trunk symmetry, shoulder height differences, prominence of one hip, or rib prominence on bending forwards may indicate a changing curvature in the spine.

Knock-knees may also progress over time. The best method of accurately assessing this is to obtain X-rays.

Flatfeet may cause pain, footwear problems, or callosities in the skin.

If central apnea is suspected, a respiratory physician may be sought out to conduct sleep studies. Central apnea results from spinal cord compression from cervical spine instability.

Generally, all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by an orthopedist, geneticist, pediatrician,
dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Kopits, Steven E. Orthropedic Complications of Dwarfism. Clinical Orthopedics and Related Research. 144: 153-179. 1976.
  3. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):17-18.
  4. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  5. Taybi, Hooshang. Lachman, Ralph S. Radiology of Syndromes, Metabolic Disorders, and Skeletal Dysplasias. St. Louis, MO: Mosby-Year Book, Inc. 1996.

Genetic Testing

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.

Genetic testing has developed enough so that doctors can often pinpoint missing or defective genes. The type of genetic test needed to make a specific diagnosis depends on the particular illness that a doctor suspects.

Many different types of body fluids and tissues can be used in genetic testing. For deoxyribonucleic acid (DNA) screening, only a very tiny bit of blood, skin, bone, or other tissue is needed.

Genetic Testing During Pregnancy

For genetic testing before birth, pregnant women may decide to undergo amniocentesis or chorionic villus sampling. There is also a blood test available to women to screen for some disorders. If this screening test finds a possible problem, amniocentesis or chorionic villus sampling may be recommended.

Amniocentesis is a test usually performed between weeks 15 and 20 of a woman's pregnancy. The doctor inserts a hollow needle into the woman's abdomen to remove a small amount of amniotic fluid from around the developing fetus. This fluid can be tested to check for genetic problems and to determine the sex of the child. When there's risk of premature birth, amniocentesis may be done to see how far the baby's lungs have matured. Amniocentesis carries a slight risk of inducing a miscarriage.

Chorionic villus sampling (CVS) is usually performed between the 10th and 12th weeks of pregnancy. The doctor removes a small piece of the placenta to check for genetic problems in the fetus. Because chorionic villus sampling is an invasive test, there's a small risk that it can induce a miscarriage.

Why Doctors Recommend Genetic Testing

A doctor may recommend genetic counseling or testing for any of the following reasons:

  • A couple plans to start a family and one of them or a close relative has an inherited illness. Some people are carriers of genes for genetic illnesses, even though they don't show, or manifest, the illness themselves. This happens because some genetic illnesses are recessive — meaning that they're only expressed if a person inherits two copies of the problem gene, one from each parent. Offspring who inherit one problem gene from one parent but a normal gene from the other parent won't have symptoms of a recessive illness but will have a 50% chance of passing the problem gene on to their children.
  • A parent already has one child with a severe birth defect. Not all children who have birth defects have genetic problems. Sometimes, birth defects are caused by exposure to a toxin (poison), infection, or physical trauma before birth. Often, the cause of a birth defect isn't known. Even if a child does have a genetic problem, there's always a chance that it wasn't inherited and that it happened because of some spontaneous error in the child's cells, not the parents' cells.
  • A woman has had two or more miscarriages. Severe chromosome problems in the fetus can sometimes lead to a spontaneous miscarriage. Several miscarriages may point to a genetic problem.
  • A woman has delivered a stillborn child with physical signs of a genetic illness. Many serious genetic illnesses cause specific physical abnormalities that give an affected child a very distinctive appearance.
  • The pregnant woman is over age 34. Chances of having a child with a chromosomal problem (such as trisomy) increase when a pregnant woman is older. Older fathers are at risk to have children with new dominant genetic mutations (those caused by a single genetic defect that hasn't run in the family before).
  • A standard prenatal screening test had an abnormal result. If a screening test indicates a possible genetic problem, genetic testing may be recommended.
  • A child has medical problems that might be genetic. When a child has medical problems involving more than one body system, genetic testing may be recommended to identify the cause and make a diagnosis.
  • A child has medical problems that are recognized as a specific genetic syndrome. Genetic testing is performed to confirm the diagnosis. In some cases, it also might aid in identifying the specific type or severity of a genetic illness, which can help identify the most appropriate treatment.

A Word of Caution

Although advances in genetic testing have improved doctors' ability to diagnose and treat certain illnesses, there are still some limits. Genetic tests can identify a particular problem gene, but can't always predict how severely that gene will affect the person who carries it. In cystic fibrosis, for example, finding a problem gene on chromosome number 7 can't necessarily predict whether a child will have serious lung problems or milder respiratory symptoms.

Also, simply having problem genes is only half the story because many illnesses develop from a mix of high-risk genes and environmental factors. Knowing that you carry high-risk genes may actually be an advantage if it gives you the chance to modify your lifestyle to avoid becoming sick.

As research continues, genes are being identified that put people at risk for illnesses like cancer, heart disease, psychiatric disorders, and many other medical problems. The hope is that someday it will be possible to develop specific types of gene therapy to totally prevent some diseases and illnesses.

Gene therapy is already being studied as a possible way to treat conditions like cystic fibrosis, cancer, and ADA deficiency (an immune deficiency), sickle cell disease, hemophilia, and thalassemia. However, severe complications have occurred in some patients receiving gene therapy, so current research with gene therapy is very carefully controlled.

Although genetic treatments for some conditions may be a long way off, there is still great hope that many more genetic cures will be found. The Human Genome Project, which was completed in 2003, identified and mapped out all of the genes (about 25,000) carried in our human chromosomes. The map is just the start, but it's a very hopeful beginning.

Reviewed by: Larissa Hirsch, MD
Date reviewed: September 26, 2016