Caudal dysplasia is a total or partial failure of development of the lower vertebrae, including the sacrum (tailbone), which results in associated abnormalities of the lower extremities (legs), spine, kidneys, gastrointestinal and genitourinary tracts.
Caudal dysplasia is also known as sacral agenesis, sacral regression, caudal aplasia, caudal regression sequence, or sirenomelia . Caudal dysplasia results from a failure of the caudal or lower region of the spinal column to form correctly. This abnormal development of the lower spine causes a wide range, or spectrum, of other abnormalities. On the mild end of the spectrum, there may be a partial absence of the tailbone with no associated symptoms (sometimes picked up accidentally on x ray), and on the severe end of the spectrum, there can be complete absence of the kidneys, openings on the spinal cord, genitourinary, limb and bowel abnormalities. Some of these more serious abnormalities can be life-threatening. Most infants with caudal dysplasia fall in between the two ends of the spectrum. They may have kidney malformations, gastrointestinal malformations, spinal cord problems, heart abnormalities, and problems with their lower limbs.
Sirenomelia is a rare condition that was once thought to represent the most severe end of the caudal dysplasia sequence. Infants with sirenomelia may have complete fusion of the lower limbs, complete or partial renal agenesis , and severe bowel problems. There is often oligohydramnios, or a low amount of amniotic fluid, during pregnancy. Because of the severity of the defects in this condition, it is generally lethal. As of 2005, sirenomelia is now thought to be a separate syndrome.
Caudal dysplasia is caused by a problem with the formation of certain tissues early in pregnancy. The lower spine is usually completely formed by the seventh week of pregnancy. Caudal dysplasia is a primary defect of formation of the tissues that will become the sacrum, spinal cord, kidneys, and gastrointestinal system.
The genetics of caudal dysplasia are not well understood. There is no convincing evidence that this is a genetic disorder. Some families have shown autosomal dominant inheritance , but more research will be necessary before the exact pattern of inheritance of this disorder is clear. In most cases, it occurs as an isolated event. In some families, there is evidence of an increased incidence of mild scoliosis and spina bifida occulta (opening on one or more of the vertebra without any physical effect) in the parents of children affected with caudal agenesis. This suggests that there may be some genetic factors that predispose some individuals to have caudal dysplasia but, as of 2005, these factors are not well understood.
Estimates of the incidence of caudal dysplasia range between approximately one in 7,500 to one in 20,000 births. Caudal dysplasia occurs equally in males and females. There is an increased rate of caudal dysplasia among infants of diabetic mothers. As many as 16–22% of infants with caudal dysplasia are born to diabetic mothers, and the risk for a diabetic woman (with poor glucose control) to have an infant with caudal dysplasia is 200 times higher that the average population risk. Diabetes or impaired glucose metabolism is a common problem in pregnancy with 3–10% of all pregnancies affected by abnormal glucose metabolism. The exact mechanism by which diabetes causes caudal dysplasia in not well understood.
Caudal dysplasia is a defect of the mesodermal tissue, which develops early in the first trimester of pregnancy. Poor glucose control during the first trimester can lead to an increased risk for the fetus to develop caudal dysplasia. The interaction between poor glucose control and the defects that lead to problems in the mesodermal tissues is not well understood.
Most women with an increased risk to have a child with caudal regression have diabetes (often undiagnosed) prior to pregnancy. Gestational diabetes (or diabetes that develops during pregnancy) is a separate entity and should not be confused with diabetes in the first trimester. Gestational diabetes is not associated with an increased risk for caudal dysplasia.
Signs and symptoms
In order to understand the signs and symptoms of caudal dysplasia, it is important to understand early embryonic development. Very early in pregnancy, the cells that will develop into the embryo are organized as a small round ball. These cells eventually separate into three distinct layers: the endoderm, the mesoderm, and the ectoderm. The endoderm can be thought of as the inside layer. Cells from the endoderm will eventually form into the lining of the digestive tract and the respiratory tract. The mesoderm can be thought of as the middle layer, and the cells of the mesoderm will eventually become the muscles, bones, kidney, heart, and blood vessels. The endoderm can be thought of as the outside layer. The cells of the endoderm will eventually become the skin, hair, nails, brain, and nervous system. Caudal dysplasia is the result of an early insult to the tissues of the mesoderm. Since the mesoderm is the tissue that forms the bones, muscles, kidneys, and other tissues, individuals with caudal dysplasia will have problems with these tissues. Any disruption of the development of the mesoderm will lead to disruption of the organs formed from this layer. Impaired glucose metabolism early in pregnancy can lead to an insult, which results in the infant having caudal dysplasia. However, since only 16–22% of mothers of infants with caudal dysplasia have diabetes, there must be other factors that also cause caudal dysplasia. These other factors are not well understood at this time.
Caudal dysplasia is a disorder with a wide spectrum of defects. Some individuals are very mildly affected and some are much more severely affected. Individuals with caudal dysplasia can have some or all of the signs and symptoms.
Spinal cord abnormalities in infants affected with caudal dysplasia include:
- missing or malformed sacrum
- abnormal vertebrae
- cerebellum agenesis
- spina bifida
Kidney abnormalities include:
- renal failure
- agenesis of the kidney
- hypoplasia of the kidney
Gastrointestinal abnormalities include:
- imperforate anus
- malformed or rotated gut
Heart abnormalities include:
- atrial septal defect
- coarctation of the aorta
- stenosis of the pulmonary valve
Lower limb abnormalities include:
- missing reflexes
- paralysis or numbness of the legs
Neurological abnormalities include:
- neurogenic bladder (impaired bladder control)
- neurogenic bowel (impaired bowel control)
- motor and sensory nerve abnormalities
Other abnormalities include:
- cleft lip/palate
- diaphragmatic hernia
- hypoplastic lungs
- low-set ears
- tracheo-eosophageal fistula (connection between the trachea and eosophagus)
The diagnosis of caudal dysplasia can be made during pregnancy, at birth, and during childhood, depending on the severity of the defects present.
The diagnosis of caudal dysplasia can be made prenatally (during pregnancy) by prenatal ultrasound (a sonogram). Sonograms use sound waves to provide an image of a fetus. The structural abnormalities of caudal dysplasia, including absence of vertebra, kidney malformations, other spinal cord malformations, and limb abnormalities, can be seen during the second trimester of pregnancy. Because the bones of the sacrum do not ossify, or harden, until approximately 22 weeks of pregnancy, it may be difficult to diagnose caudal dysplasia before this time.
The diagnosis of caudal dysplasia can also be made by physical examination after birth. Physical signs can include flattening of the buttocks, shortening of the gluteal cleft, scoliosis, spina bifida, and hydrocephalus. X rays should be taken to look at the formation of the underlying bones and tissues.
Treatment and management
When caudal dysplasia is diagnosed by prenatal ultrasound, the mother should be tested for diabetes. Pregnancy termination may be an option. If the pregnancy continues, the parents may wish to consult with specialists to get more specific information about prognosis.
Because of the abnormalities seen and the possible complications, delivery should be at a tertiary care center or hospital able to provide specialized pediatric care. It is likely that an infant with caudal dysplasia will spend a significant amount of time in the hospital as a newborn. If the tertiary care center is not located near the family, this can increase the burden of care for the family.
There is no cure for caudal dysplasia. Treatment is governed by the abnormalities present. If the abnormalities are severe (life-threatening), corrective surgery is not an option. The main goals of treatments include maintaining and improving kidney, lung, and gastrointestinal function. Orthopedic surgeries are done to correct malformation, and physical therapy is used to avoid secondary complications, such as scoliosis.
Many of the defects of caudal dysplasia can be surgically treated but not cured. For example, an opening on the spine (spina bifida) can be surgically closed, but if the nerves in that opening have been damaged, there is nothing that can be done to reverse this damage. Other surgeries include orthopedic surgeries to correct bone malformations and improve limb function. Surgery can also be done to correct hydrocephalus or imperforate anus.
Other treatments involve orthopedic devices and treatments for neurogenic bladder. Orthopedic devices may be used to help with problems of the hip, back, and legs. Neurogenic bladder is one of the more serious and debilitating problems in caudal dysplasia. Long-term bladder dysfunction can result in kidney damage and failure.
The treatments for caudal dysplasia often require lifelong medical attention. It is important to prepare the family for this and to stress the need for preventative care (i.e., prevention of infections) and vigilance in detecting complications.
The prognosis for caudal dysplasia is highly dependant on the severity of the malformation present. Those with extremely mild abnormalities may have no or few symptoms. Infants with more serious symptoms may require extensive urologic and orthopedic assistance, including multiple surgeries and lifelong therapies. Neurogenic bladder is one of the more serious and debilitating problems in caudal dysplasia. Long-term bladder dysfunction can result is kidney damage and failure, and intensive efforts may be required to avoid this problem. Some infants with caudal dysplasia are born with lethal abnormalities that are incompatible with life. Infants that do survive generally have normal mental function.
National Institute of Arthritis and Musculoskeletal and Skin Diseases. (April 8, 2005.) <http://www.nih.gov/niams>.
National Institute of Arthritis and Musculoskeletal and Skin Diseases. 1 AMS Circle, Bethesda, MD 20892-3675. Telephone: (301) 496-8188. Fax: (877) 226-4267. E-mail: [email protected] (April 8, 2005.) <http://www.nih.gov/niams>.
Kathleen A. Fergus, MS, CGC