Spondylo-Epiphyseal Dysplasia

Sphondylos is a Greek term meaning vertebra. Epiphysis refers to the ends of long bones that are adjacent to the joints. Therefore, spondylo-epiphyseal 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 Spondylo-Epiphyseal 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 Spondylo-Epiphyseal 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 & 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, & 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 & 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 tarsalossification 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
Neck

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.

Spine

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.

Feet

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.

Spine

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
Eye

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.

Ear

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.

 
References
  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.

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