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.

All About Genetics

What do you know about your family tree? Have any of your relatives had health problems that tend to run in families? Which of these problems affected your parents or grandparents? Which ones affect you or your brothers or sisters now? Which problems might you pass on to your children?

Thanks to advances in medical research, doctors now have the tools to understand much about how certain illnesses, or increased risks for certain illnesses, pass from generation to generation. Here are some basics about genetics.

Genes and Chromosomes

Each of us has a unique set of chemical blueprints affecting how our body looks and functions. These blueprints are contained in our DNA (deoxyribonucleic acid), long, spiral-shaped molecules found inside every cell. DNA carries the codes for genetic information and is made of linked pieces (or subunits) called nucleotides. Each nucleotide contains a phosphate molecule, a sugar molecule (deoxyribose), and one of four so-called "coding" molecules called bases (adenine, guanine, cytosine, or thymidine). The order (or sequence) of these four bases determines each genetic code.

The segments of DNA that contain the instructions for making specific body proteins are called genes. Scientists believe that human DNA carries about 25,000 protein-coding genes. Each gene may be thought of as a "recipe" you'd find in cookbook. Some are recipes for creating physical features, like brown eyes or curly hair. Others are recipes to tell the body how to produce important chemicals called enzymes (which help control the chemical reactions in the body).

Along the segments of our DNA, genes are neatly packaged within structures called chromosomes. Every human cell contains 46 chromosomes, arranged as 23 pairs (called autosomes), with one member of each pair inherited from each parent at the time of conception. After conception (when a sperm cell and an egg come together to make a baby), the chromosomes duplicate again and again to pass on the same genetic information to each new cell in the developing child. Twenty-two autosomes are the same in males and females. In addition, females have two X chromosomes and males have one X and one Y chromosome. The X and the Y are known as sex chromosomes.

Human chromosomes are large enough to be seen with a high-powered microscope, and the 23 pairs can be identified according to differences in their size, shape, and the way they pick up special laboratory dyes.

Genetic Problems

Errors in the genetic code or "gene recipe" can happen in a variety of ways. Sometimes information is missing from the code, other times codes have too much information, or have information that's in the wrong order.

These errors can be big (for example, if a recipe is missing many ingredients — or all of them) or small (if just one ingredient is missing). But regardless of whether the error is big or small, the outcome can be significant and cause a person to have a disability or at risk of a shortened life span.

Abnormal Numbers of Chromosomes

When a mistake occurs as a cell is dividing, it can cause an error in the number of chromosomes a person has. The developing embryo then grows from cells that have either too many chromosomes or not enough.

In trisomy, for example, there are three copies of one particular chromosome instead of the normal two (one from each parent). Trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) are examples of this type of genetic problem.

Trisomy 18 affects 1 out of every 7,500 births. Children with this syndrome have a low birth weight and a small head, mouth, and jaw. Their hands typically form clenched fists with fingers that overlap. They also might have birth defects involving the hips and feet, heart and kidney problems, and intellectual disability (also called mental retardation). Only about 5% of these children are expected to live longer than 1 year.

Trisomy 13 affects 1 out of every 15,000 to 25,000 births. Children with this condition often have cleft lip and palate, extra fingers or toes, foot abnormalities, and many different structural abnormalities of the skull and face. This condition also can cause birth defects of the ribs, heart, abdominal organs, and sex organs. Long-term survival is unlikely but possible.

In monosomy, another form of numerical error, one member of a chromosome pair is missing. So there are too few chromosomes rather than too many. A baby with a missing autosome has little chance of survival. However, a baby with a missing sex chromosome can survive in certain cases. For example, girls with Turner syndrome — who are born with just one X chromosome — can live normal, productive lives as long as they receive medical care for any health problems associated with their condition.

Deletions, Translocations, and Inversions

Sometimes it's not the number of chromosomes that's the problem, but that the chromosomes have something wrong with them, like an extra or missing part. When a part is missing, it's called a deletion (if it's visible under a microscope) and a microdeletion (if it's too tiny to be visible). Microdeletions are so small that they may involve only a few genes on a chromosome.

Some genetic disorders caused by deletions and microdeletions include Wolf-Hirschhorn syndrome (affects chromosome 4), Cri-du-chat syndrome (chromosome 5), DiGeorge syndrome (chromosome 22), and Williams syndrome (chromosome 7).

In translocations (which affect about 1 in every 400 newborns), bits of chromosomes shift from one chromosome to another. Most translocations are "balanced," which means there is no gain or loss of genetic material. But some are "unbalanced," which means there may be too much genetic material in some places and not enough in others. With inversions (which affect about 1 in every 100 newborns), small parts of the DNA code seem to be snipped out, flipped over, and reinserted. Translocations may be either inherited from a parent or happen spontaneously in a child's own chromosomes.

Both balanced translocations and inversions typically cause no malformations or developmental problems in the kids who have them. However, those with either translocations or inversions who wish to become parents may have an increased risk of miscarriage or chromosome abnormalities in their own children. Unbalanced translocations or inversions are associated with developmental and/or physical abnormalities.

Sex Chromosomes

Genetic problems also occur when abnormalities affect the sex chromosomes. Normally, a child will be a male if he inherits one X chromosome from his mother and one Y chromosome from his father. A child will be a female if she inherits a double dose of X (one from each parent) and no Y.

Sometimes, however, children are born with only one sex chromosome (usually a single X) or with an extra X or Y. Girls with Turner syndrome are born with only one X chromosome, whereas boys with Klinefelter syndrome are born with 1 or more extra X chromosomes ( XXY or XXXY).

Sometimes, too, a genetic problem is X-linked, meaning that it is associated with an abnormality carried on the X chromosome. Fragile X syndrome, which causes intellectual disability in boys, is one such disorder. Other diseases that are caused by abnormalities on the X chromosome include hemophilia and Duchenne muscular dystrophy.

Females may be carriers of these diseases, but because they also inherit a normal X chromosome, the effects of the gene change are minimized. Males, on the other hand, only have one X chromosome and are almost always the ones who show the full effects of the X-linked disorder.

Gene Mutations

Some genetic problems are caused by a single gene that is present but altered in some way. Such changes in genes are called mutations. When there is a mutation in a gene, the number and appearance of the chromosomes is usually still normal.

To pinpoint the defective gene, scientists use sophisticated DNA testing techniques. Genetic illnesses caused by a single problem gene include phenylketonuria (PKU), cystic fibrosis, sickle cell disease, Tay-Sachs disease, and achondroplasia (a type of dwarfism).

Although experts used to think that no more than 3% of all human diseases were caused by errors in a single gene, new research shows that this is an underestimate. Within the last few years, scientists have discovered genetic links to many different diseases that weren't originally thought of as genetic, including Parkinson's disease, Alzheimer's disease, heart disease, diabetes, and several different types of cancer. Alterations in these genes are thought to increase one's risk of developing these conditions.

Oncogenes (Cancer-Causing Genes)

Researchers have identified about 50 cancer-causing genes that greatly increase a person's odds of developing cancer. By using sophisticated tests, doctors may be able to identify who has these genetic mutations, and determine who is at risk.

For example, scientists have determined that colorectal cancer is sometimes associated with mutations in a gene called APC. They've also discovered that abnormalities in the BRCA1 and BRCA2 gene give women a 50% chance of developing breast cancer and an increased risk for ovarian tumors.

People who are known to have these gene mutations now can be carefully monitored by their doctors. If problems develop, they're more likely to get treated for cancer earlier than if they hadn't known of their risk, and this can increase their odds of survival.

New Discoveries, Better Care

Scientists have made major strides in the field of genetics over the last two decades. The mapping of the human genome and the discovery of many disease-causing genes has led to a better understanding of the human body. This has enabled doctors to provide better care to their patients and to increase the quality of life for people (and their families) living with genetic conditions.

Reviewed by: Nina Powell-Hamilton, MD
Date reviewed: September 26, 2016