NORD gratefully acknowledges Frank Chervenak, MD, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, for assistance in the preparation of this report.
Caudal regression syndrome is a broad term for a rare complex disorder characterized by abnormal development of the lower (caudal) end of the spine. The spine consists of many small bones (vertebrae) that collectively form the spinal column. The spinal column is generally broken down into three segments – the cervical spine, consisting of the vertebrae just below the skull; the thoracic spine, consisting of the vertebrae in the chest region; and the lumbar spine, consisting of the vertebrae of the lower back. A triangularly-shaped bony structure called the sacrum joins the lumbar portion of spine to the pelvis. The sacrum consists of five vertebrae fused together. At the end of the sacrum is the tailbone (coccyx). A wide range of abnormalities may potentially occur in infants with caudal regression syndrome including abnormal development (agenesis) of the sacrum and coccyx and abnormalities of the lumbar spine. More severe malformations may occur in some cases. Abnormalities of the lower spine can cause a variety of additional complications including joint contractures, clubfeet and disruption or damage of the end of the spinal cord may occur, potentially causing urinary incontinence. Additional anomalies of the gastrointestinal tract, kidneys, heart, respiratory system, upper limbs and upper portions of the spine can also occur. The exact cause of caudal regression syndrome is unknown. Both environmental and genetic factors are suspected to play a role in the development of the disorder.
Some sources in the medical literature classify a condition called sirenomelia as the most severe form of caudal regression syndrome. However, recently many researchers have indicated that sirenomelia is a similar, but distinct, disorder. NORD has a separate report on sirenomelia.
The specific symptoms and severity of caudal regression syndrome can vary dramatically from one person to another. Caudal regression syndrome most likely represents a spectrum of disease ranging from cases with milder symptoms to cases with severe, disabling or potentially life-threatening complications. It is important to note that affected individuals may not have all of the symptoms discussed below and that one child’s experience will vary (sometimes dramatically) from another child’s. Parents of affected children should talk to their physician and medical team about their child’s specific case, associated symptoms and overall prognosis.
Infants with caudal regression syndrome have abnormalities affecting the sacral and lumbar spine. In some cases, affected infants may only have isolated abnormal development of the sacrum (sacral) agenesis. In other cases, the sacrum may be absent altogether. Sacral agenesis is often associated with narrowing of the hips, underdeveloped of the muscles of the buttock (hypoplastic gluteal muscles), an indentation on the skin of the lower back (sacral dimple) and flattening of the buttocks. In some cases, abnormalities of the lumber vertebrae may also occur.
The abnormal development of the caudal region of the spine can cause additional abnormalities affecting the spinal cord and lower limbs. In some cases, disruption or damage to the lower portion of the spinal cord may occur causing a variety of neurological abnormalities including defective bladder and bowel control, increased urinary frequency, and failure of the bladder to empty completely (neurogenic bladder). The urological abnormalities potentially associated with caudal regression syndrome can be significant.
Damage to the nerves can also cause abnormalities of the lower limbs. Such abnormalities may include flexion contractures of the knee and hip. A contracture is a condition in which a joint becomes permanently fixed in a bent (flexed) or straightened (extended) position, completely or partially restricting the movement of the affected joint. Affected infants may also have reduced muscle mass in the legs, clubfeet or webbed skin on the back of the knees (popliteal ptergyium). When present, the severity of lower limb abnormalities can vary. Some individuals will walk unassisted; others may need an assistance device such as crutches, braces, walkers or, in severe cases, a wheelchair.
Infants with caudal regression syndrome may have a wide variety of additional physical findings including kidney abnormalities, abnormalities of the upper vertebrae, facial anomalies such as cleft lip, cleft palate, and a condition in which a thin covering blocking the anal opening or the passage that normally connects the anus and lowest part of the large intestine (rectum) fails to develop, which is known as anal atresia or imperforate anus.
Kidney abnormalities that occur in caudal regression syndrome may include the absence of one kidney (renal agenesis). In some cases, affected infants may have kidneys that are not located in their normal position (renal ectopia) or fusion of the tubes that force urine from the kidneys to the bladder (fused ureters). Kidney abnormalities can cause urinary obstruction, neurogenic bladder, or the abnormal backflow of urine from the bladder into the ureters (vesicoureteral reflux).
Some individuals with caudal regression syndrome may have a meningomyelocele, a condition in which the membranes that cover the spine and, in some cases, the spinal cord itself protrude through a defect in the spinal canal. Congenital heart defects and respiratory complications can also be associated with caudal regression syndrome.
The exact cause of caudal regression syndrome is unknown. Researchers believe that both environmental and genetic factors may play a role in the development of the disorder. Most cases appear to occur randomly for no apparent reason (sporadically), which suggests environmental factors or a new mutation. Most likely, caudal regression syndrome is multifactorial, which means that several different factors may play a causative role. In addition, different genetic factors may contribute to the disorder in different people (genetic heterogeneity).
One risk factor that has been identified for caudal regression syndrome is maternal diabetes. Caudal regression syndrome occurs with greater frequency in women with diabetes than in the general population. Approximately 16 percent of affected individuals of caudal regression syndrome have occurred in children of women with diabetes. The exact reason why women with diabetes are at a greater risk for having a child with caudal regression syndrome is not fully understood.
The environmental factors that play a role in the development of caudal regression syndrome are unknown, although numerous different potential factors have been suggested including alcohol, retinoic acid, lack of oxygen (hypoxia) and amino acid imbalances. More research is necessary to determine what environmental factors play a role in the development of caudal regression syndrome.
Some infants with caudal regression syndrome may have a genetic predisposition to developing the disorder.
A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or “activated” under certain circumstances, such as due to particular environmental factors.
In some cases, caudal regression syndrome may be associated with mutations of the VANGL1 gene located on the short arm (p) of chromosome 1 (1p13). The exact role this gene mutation plays in the development of caudal regression syndrome is unknown. This mutation is inherited as an autosomal dominant trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
A different gene mutation, HLXB9, is known to cause a rare disorder called Currarino syndrome. This disorder is characterized by partial sacral agenesis, a presacral mass, and anorectal malformations. (For more information on this disorder, see the Related Disorders section below.)
Researchers believe that the environmental or genetic factors associated with caudal regression syndrome have a teratogenic effect on the developing fetus. A teratogen is any substance that can disrupt the development of an embryo or fetus. On theory suggests that environmental or genetic factors impair or block blood flow to the caudal region of the developing fetus (vascular disruption).
Caudal regression syndrome affects males and females in equal numbers. The incidence of the disorder has been estimated to be 1 in 5 per 100,000 live births. The disorder occurs with greater frequency among women with diabetes.
A diagnosis of caudal regression syndrome can often be made before birth (prenatally) usually using a fetal ultrasound.
Clinical Testing and Work-Up
An ultrasound is an exam that uses high-frequency sound waves to produce an image of the developing fetus. A fetal ultrasound can detect some of the defects associated with caudal regression syndrome. Additional tests may be required to detect or assess or physical findings potentially associated with the disorder. For example, an echocardiography is usually performed to evaluate the extent of the involvement of the heart. An echocardiography is an exam that uses sound waves to produce images of the heart.
Magnetic resonance imaging (MRI) may also be performed to assess the degree of certain anomalies such as spinal defects. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues.
A diagnosis of caudal regression syndrome may be made at birth by a thorough clinical evaluation and identification of characteristic findings.
The treatment of caudal regression syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurosurgeons, neurologists, urologists, orthopedists, orthopedist surgeons, cardiologists, kidney specialists (nephrologists) and other health care professionals may need to systematically and comprehensively plan an affect child’s treatment.
The specific treatment strategy for infants with caudal regression syndrome will vary from one infant to another based upon various factors. Because caudal regression syndrome is a spectrum of disease with a wide variety of severity, the prognosis can vary greatly as well. Affected infants may require complex medical care and surgical intervention. Multiple surgeries may be necessary to treat various urological, spinal and cardiac abnormalities, anal atresia and certain limb deformities associated with caudal regression syndrome. In addition, anticholingergic drugs may be administered to treat urological abnormalities.
Early intervention is important in ensuring that children with caudal regression syndrome reach their highest potential. Services that may be beneficial may include physical therapy, psychological services and other medical, social, and/or vocational services.
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