What are the other Names for this Condition? (Also known as/Symptoms)

• Caudal Dysplasia Sequence
• Congenital Sacral Agenesis
• Sacral Defect with Anterior Meningocele

What is Caudal Regression Syndrome? (Definition/Background Information)

• Caudal Regression Syndrome is a genetic disorder that is characterised by impaired development of the posterior (tail/caudal) part of the body. Since the disorder affects the posterior part of the body, the gastrointestinal, genitourinary, and skeletal systems may be affected
• Caudal Regression Syndrome is considered to be a multifactorial disorder, which means that it is caused by both genetic and environmental factors, generally within the first 4 weeks of embryonic development. Having a mother with diabetes and a family history of the condition are both risk factors for developing the syndrome
• Some scientists believe that Caudal Regression Syndrome is caused by a disruption of the mesoderm (middle layer of embryonic tissue), which can lead to impaired blood supply to the caudal region. Another theory suggests that an abnormal artery in the developing fetus’s abdomen hinders blood supply, ultimately causing improper development of the mesoderm
• Some of the symptoms of Caudal Regression Syndrome include bone malformations of the vertebral column (including the spine), the pelvic bone, the long bones of the legs and feet, inguinal hernia, abnormal rotation of the intestine, blocked opening to the anus, malformed or absent kidneys, fused ureters, and absent genitalia
• Severe cases can result in complications including breathing difficulty in newborns, congenital heart defects, and urination difficulties. In childhood and later stages of development, the affected individual may require prosthetic limbs and wheelchair in order to move around normally
• A diagnosis of Caudal Regression Syndrome can be made through prenatal ultrasound and genetic testing. After birth, physical examinations and imaging studies are routinely performed to diagnose the type and extent of damage to lower parts of the body
• There is no cure for Caudal Regression Syndrome and treatment is offered to correct the abnormalities. A coordinated effort made by a team of specialists and surgeons may be required in order to successfully manage the condition
• The prognosis of Caudal Regression Syndrome is based on the severity of the signs and symptoms. Individuals with mild conditions are known to have normal intelligence and are able to lead a better quality of lives. In case of severe disorder, the prognosis can be poor and many newborns may die from the disorder

Who gets Caudal Regression Syndrome? (Age and Sex Distribution)

• Caudal Regression Syndrome is reported to affect 1-5 newborns per 100,000 among the general population
• However, the prevalence rate increases considerably in those born to diabetic mothers; the rate of occurrence is around 1 in 350
• The condition can affect both male and female babies equally
• No specific racial or ethnicity bias is observed

What are the Risk Factors for Caudal Regression Syndrome? (Predisposing Factors)

• A major risk factor for developing Caudal Regression Syndrome is being born to a diabetic mother
• Having a family history of the condition is also a major risk factor

• Genetic mutations in combination with environmental factors may lead to an increased risk of developing Caudal Regression Syndrome. Such factors may include:

  • Alcohol consumption and amino acid imbalances in the expectant mothers
  • A lack of oxygen during fetal development due to a variety of reasons
• In cases where the condition occurs sporadically, no risk factors have been reported

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Caudal Regression Syndrome? (Etiology)

Caudal Regression Syndrome is believed to be multifactorial in nature, which means that it can be caused by the interaction of several genetic and/or environmental triggers. Since children born to diabetic mothers bear an increased risk of developing Caudal Regression Syndrome. Researchers are currently investigating the gene(s) or other factors that may be responsible for the disorder.

• There is one school of thought that states that interference in fetal development on approximately the 28th day of pregnancy may be the cause of the syndrome

  • The middle layer of the embryo known as the mesoderm, contributes to normal development of gastrointestinal, genitourinary, and parts of the skeletal system
  • When its development is disrupted, the consequent abnormal mesoderm leads to the syndrome and the set of associated symptoms. Thus, researchers believe that an abnormal mesoderm causes reduced blood flow and other symptoms of Caudal Regression Syndrome
• There is also an alternative theory suggesting that an abnormal artery in the abdomen of the developing fetus diverts blood flow away from the lower parts of the body, resulting in anomalous development of the skeletal, gastrointestinal, and genitourinary systems. This school of thought believes that abnormal blood flow impairs mesoderm development and differentiation, leading to Caudal Regression Syndrome

The above abnormal development results in signs and symptoms described with Caudal Regression Syndrome.

• Any damage to the developing fetus due to increased blood sugar, infections in early stages of gestation, exposure to toxins, and restrictions to the blood supply are also believed to contribute to the syndrome

• Neural tube and neural plates are very important initial structures during fetal development from which the brain and the spinal cord develop

  • The primary neurulation is when the neural tube is formed from the neural plate
  • Differentiation of the normally developed primary or secondary neural tube, leading to its degeneration can occur

What are the Signs and Symptoms of Caudal Regression Syndrome?

The typical signs and symptoms associated with Caudal Regression Syndrome include:

• Skeletal system signs and symptoms:

  • Scoliosis or curvature in the spine
  • Missing or abnormally shaped lower vertebrae
  • Missing sacrum (the triangle-shaped bone at the lower end of spine); incomplete closing of the vertebrae
  • Partly missing spinal cord
  • Abnormal hair growth at the base of the spinal cord
  • A fluid-filled sac covered by skin on the back
  • Misshapen chest bones; breathing distress
  • Limited range of motion
  • Flat buttocks
  • Poorly developed leg bones, particularly the femurs (long bones); frog leg-like position of legs, with knees pointing outward
  • Webbing between thigh and calf
  • Clubfeet; feet that turn upwards (calcaneovalgus)
  • Decreased sensation in the lower extremities

• Gastrointestinal system signs and symptoms:

  • Protrusion of the intestine through the abdominal wall (inguinal hernia)
  • Blockage in anal opening (imperforate anus)
  • Twisting of the intestine (malrotation)
  • Constipation
  • Lack of bowel muscle control

• Genitourinary system signs and symptoms:

  • Abnormal kidney formation
  • Missing kidney; fused kidneys, forming a single horseshoe-shaped unit
  • More than two renal tubes (ureters); fused renal tubes
  • Nerve damage to the bladder, leading to loss of control
  • Bladder protruding through the abdominal wall (bladder exstrophy)
  • Obstruction to urine flow; backflow of urine to the kidneys (vesicoureteral reflux)
  • Lack of genitals
  • In males: Undescended testes (cryptorchidism) and/or the presence of the urethral opening under the penis (hypospadias)
  • In females: An abnormal connection between the rectum and vagina (rectovaginal fistula)

In addition to the above symptoms, the following may be present:

• Facial malformations such as cleft lip and cleft palate
• Congenital heart defects
• Extension of brain material into the spinal cord (Chiari malformation)

The types and severity of symptoms may vary among individuals affected by this disorder

How is Caudal Regression Syndrome Diagnosed?

• A diagnosis of Caudal Regression Syndrome may be suspected through ultrasound imaging of the fetus
• A physical examination of a newborn at birth or shortly after birth can usually confirm the diagnosis
• Ultrasound and magnetic resonance imaging scans in order to assess the type and extent of damage to the skeleton, as well as to the internal organs
• Echocardiography to assess heart defects

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Caudal Regression Syndrome?

The potential complications from Caudal Regression Syndrome may include:

• Heart abnormalities due to congenital heart defects
• Respiratory distress
• Severely impeded range of movements; necessity of prosthetic limbs  or wheelchair for movement
• Dysfunctional kidneys; missing kidneys can cause waste to circulate in the blood stream
• Inability to urinate or control urination
• Inability to pass stools or lack of bowel control
• Paralysis

How is Caudal Regression Syndrome Treated?

A team of specialists consisting of a neurologist, nephrologist, psychologist, cardiologist, and surgeons, may all be involved in treating a child with Caudal Regression Syndrome. The condition cannot be cured, although corrective measures for individual symptoms may be an effective means of treating the condition.

The following are treatment options for a child with Caudal Regression Syndrome:

• Surgery for blocked anus (colostomy)
• Surgery for skeletal abnormalities
• Removal of webbing between thigh and calf, to increase the range of motion
• Braces or crutches for those with mild skeletal impairment
• Prosthetics, in cases of substantial damage to the legs; wheelchairs for children with severely hampered movements
• Surgery to repair disorders of the urinary tract
• Anticholinergic drugs for lack of bladder control
• Surgical intervention for cardiac defects
• Physiotherapy to improve range of muscle movement
• Psychological therapy, vocational support, when needed
• Support of family and social support

How can Caudal Regression Syndrome be Prevented?

• Currently, there are no specific methods or guidelines available to prevent Caudal Regression Syndrome, since it is a genetic condition
• If there is a family history of the condition, genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Caudal Regression Syndrome
• Good glycemic control during pregnancy can possibly help prevent Caudal Regression Syndrome
• Pregnant women should avoid indulgence in substances (alcohol, drugs) that may be toxic to the developing fetus
• Regular medical screening at periodic intervals with tests, and physical examinations are strongly recommended

What is the Prognosis of Caudal Regression Syndrome? (Outcome/Resolutions)

• The prognosis of Caudal Regression Syndrome is based on the severity of the signs and symptoms, with mild cases having better prognosis than severe cases
• However, in general, the prognosis is considered to be poor, with death resulting from complications of the disorder
• Those who survive are reported to have normal intelligence and are capable of reaching their maximum potential having a better quality of life

Additional and relevant useful information for Caudal Regression Syndrome:

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.