Caudal Regression Syndrome: Symptoms, Types, Causes and Treatment

Caudal Regression Syndrome (CRS) is a rare and complex congenital disorder that affects the development of the lower (caudal) part of the body. Its impact is both profound and varied, touching not only the spine but also critical systems such as the nervous, gastrointestinal, genitourinary, and skeletal systems. CRS can present a range of symptoms and severities, from subtle impairments to life-altering malformations. In this article, we'll explore the symptoms, types, causes, and treatment options for CRS, making sense of a complicated condition with the help of current research.

Symptoms of Caudal Regression Syndrome

Recognizing the symptoms of CRS is crucial for early diagnosis and appropriate intervention. The syndrome manifests through a wide array of physical, neurological, and functional abnormalities, primarily affecting the lower body. However, the severity and combination of symptoms can vary dramatically from one individual to another.

Symptom	Description	Systems Affected	Sources
Sacral Agenesis	Absence or underdevelopment of the sacrum	Skeletal, Nervous	2 3 4 6 9
Lower Limb Deformities	Contractures, weakness, or fusion (sirenomelia)	Musculoskeletal	1 2 6 13
Neurogenic Bladder	Bladder dysfunction due to nerve damage	Genitourinary, Nervous	2 3 4 10 11
Bowel Dysfunction	Constipation, incontinence	Gastrointestinal, Nervous	3 4 10 14
Scoliosis	Sideways curvature of the spine	Skeletal	2 8
Anorectal Malformations	Imperforate anus, fistulas	Gastrointestinal	1 5 6 8
Genitourinary Abnormalities	Kidney malformations, horseshoe kidney	Genitourinary	1 8 9 10
Tethered Cord	Spinal cord is abnormally attached	Nervous	8 9

Table 1: Key Symptoms

Sacral Agenesis and Vertebral Anomalies

One of the hallmark features of CRS is sacral agenesis—the partial or complete absence of the sacrum. This leads to instability in the pelvis and spine, and can cause unique gait patterns, postural issues, or sitting difficulties. Imaging often reveals absent coccyx and hypoplastic (underdeveloped) sacrum 2 3 4 6 9.

Lower Limb Deformities

The lower limbs may be affected by a broad spectrum of deformities, including contractures, muscle weakness, and in severe cases, fusion of the legs (sirenomelia or "mermaid syndrome") 1 2 6 13. Patients can also present with hip dislocations and instability.

Neurological and Functional Impairments

Due to the involvement of the spinal cord, many children and adults with CRS experience neurogenic bladder and bowel dysfunction. This can manifest as chronic constipation, incontinence, or urinary retention, which may lead to kidney damage if not managed 2 3 4 10 11 14.

Scoliosis and Skeletal Issues

Scoliosis, or abnormal curvature of the spine, is a common skeletal manifestation. Other anomalies include fused or malformed vertebrae, hemivertebrae, and narrowed spinal canals. These issues can compound mobility challenges and pain 2 8.

Anorectal and Urogenital Malformations

Many individuals present with imperforate anus, rectourethral or rectovesical fistulas, and genitourinary malformations such as horseshoe kidneys or cryptorchidism 1 5 6 8 9 10. These require coordinated medical and surgical management.

Variation in Presentation

The symptoms of CRS can range from subtle (e.g., mild constipation with minimal skeletal abnormalities) to profound (e.g., complete lower limb fusion with multiple organ malformations). The degree of neurological impairment is closely tied to the level and severity of spinal involvement 3 4 6 10.

Types of Caudal Regression Syndrome

CRS is not a single entity, but rather a spectrum of malformations. The types are generally classified based on the severity and structures involved.

Type	Key Characteristics	Severity	Sources
Type I	Partial sacral agenesis, mild deficits	Mild-Moderate	2 4 7 9
Type II	Total sacral agenesis, lumbar involvement	Moderate-Severe	2 4 6 7 9
Sirenomelia	Fusion of lower limbs, visceral anomalies	Most Severe	1 5 6 13
Currarino Triad	Anorectal atresia, sacral agenesis, presacral mass	Variable	6

Table 2: Major Types of CRS

Classification by Severity

CRS is often divided into two main types based on the level of spinal and sacral involvement 2 4 7 9:

• Type I: Partial sacral agenesis, where some sacral segments are present. Individuals may have mild to moderate neurological deficits and better preserved function.
• Type II: Total sacral agenesis, sometimes extending into the lumbar region. This is associated with more pronounced deficits, including severe limb deformities, neurogenic bladder, and bowel dysfunction.

Sirenomelia (Mermaid Syndrome)

Sirenomelia represents the most severe end of the CRS spectrum. It is characterized by fusion of the lower limbs and profound malformations of the gastrointestinal, genitourinary, and vascular systems. Survival is rare, but there are reports of successful surgical separation and rehabilitation 1 5 6 13.

Currarino Triad

A related but distinct anomaly is the Currarino triad, which includes anorectal atresia, partial sacral agenesis (especially the coccyx), and a presacral mass such as a meningocele or dermoid cyst 6. This triad can overlap with milder forms of CRS.

Associated Malformations

Regardless of type, CRS can be associated with additional anomalies, such as:

• Split cord malformations (e.g., diastematomyelia, diplomyelia)
• Tethered cord
• Horseshoe kidney
• Hemivertebrae and other vertebral anomalies 8 9

Individualized Presentation

Each case of CRS is unique, and the combination of affected systems, severity, and associated anomalies guides both prognosis and management 7.

Causes of Caudal Regression Syndrome

Understanding the causes of CRS helps in risk assessment and may guide future prevention strategies. The origins of CRS are complex and involve an interplay of genetic, environmental, and possibly vascular factors.

Cause	Description	Evidence Type	Sources
Maternal Diabetes	Increased CRS risk in offspring	Epidemiological	5 6 8 10 11
Genetic Factors	Mutations affecting caudal development	Genetic studies	5 12
Retinoic Acid Dysregulation	Abnormal embryonic cell migration/differentiation	Animal models	1 5 12
Vascular Hypoperfusion	Disrupted blood supply to caudal region	Experimental/clinical	1 10 11
Environmental/Teratogens	Trauma, toxins, drugs during pregnancy	Observational	1 12

Table 3: Main Causes and Risk Factors

Maternal Diabetes

One of the most established risk factors for CRS is maternal diabetes, particularly poorly controlled pregestational diabetes. The prevalence of CRS in infants of diabetic mothers is significantly higher than in the general population, suggesting a strong teratogenic influence of hyperglycemia on caudal development 5 6 8 10 11.

Genetic Factors

Although most CRS cases are sporadic, there is evidence for genetic susceptibility. Various genes involved in caudal differentiation and neural cell migration have been implicated. Familial cases are rare but highlight the possibility of hereditary contribution 5 12.

Retinoic Acid and Teratogens

Experimental studies in animal models have shown that exposure to excessive retinoic acid (a vitamin A derivative) during pregnancy can induce CRS-like malformations, including vertebral, neural tube, urogenital, and hind limb defects 1 5 12. This suggests a critical window during embryogenesis when exposure to teratogens can disrupt normal development.

Vascular Disruption

Some severe cases, particularly those resembling sirenomelia, may result from vascular hypoperfusion—an inadequate blood supply to the developing caudal region, which leads to tissue loss and malformations 1 10 11.

Environmental and Unknown Factors

Other proposed causes include trauma, nutritional deficiencies, and exposure to certain medications or toxins during pregnancy. However, the majority of cases remain unexplained, underscoring the multifactorial nature of CRS 1 12.

Treatment of Caudal Regression Syndrome

While there is no cure for CRS, a multidisciplinary and individualized approach can greatly improve quality of life and functionality. Treatment focuses on addressing the specific symptoms and complications present in each patient.

Approach	Focus/Goal	Modalities	Sources
Multidisciplinary Care	Comprehensive management	Orthopedics, urology, rehab	4 6 7 10 11
Surgical Intervention	Correct anatomical defects	Orthopedic, urologic, GI	6 10 13 15
Rehabilitation	Enhance motor and functional abilities	Physical therapy, GH therapy	6 14 15
Bladder/Bowel Management	Prevent renal damage, improve continence	Catheterization, medications	3 10 11 14
Assistive Devices	Improve mobility, independence	Orthoses, wheelchairs	13 15
Genetic Counseling	Family planning, risk assessment	Genetic evaluation	5 10

Table 4: Treatment Strategies

Multidisciplinary Approach

Effective management of CRS requires a team of specialists, including pediatricians, orthopedic surgeons, urologists, neurosurgeons, physiatrists, and therapists. Each patient’s treatment plan is tailored to their unique constellation of symptoms and needs 4 6 7 10 11.

Surgical Interventions

Surgery is often necessary to correct anatomical defects, such as:

• Spinal and pelvic stabilization (e.g., lumbopelvic arthrodesis or external fixation) to improve sitting and walking ability 6 15
• Correction of lower limb deformities and contractures 13
• Repair of anorectal malformations or urogenital anomalies 6 13
• Separation of fused limbs in sirenomelia, in rare cases 13

Rehabilitation and Physical Therapy

Physical therapy and rehabilitation are cornerstones of care. Programs focus on maximizing mobility, independence, and muscle strength. Growth hormone (GH) therapy, combined with rehabilitation, has shown promise in improving neuromuscular function and innervation in some cases 14. Assistive devices such as orthoses and wheelchairs support daily activities and participation 13 15.

Bladder and Bowel Management

Bladder and bowel dysfunctions are managed with scheduled catheterization, medications, and bowel programs to prevent renal damage and improve continence 3 10 11 14.

Long-Term and Supportive Care

Patients often require ongoing support, including:

• Monitoring for scoliosis and spinal instability
• Regular urologic and renal assessment
• Psychological support and social services
• Genetic counseling for affected families 5 10

Prognosis

Most children with CRS have normal intelligence and can achieve a good quality of life with comprehensive care, although long-term neurological and orthopedic issues may persist 10 11 14 15.

Conclusion

Caudal Regression Syndrome is a rare but impactful condition that touches multiple organ systems and requires a comprehensive approach for management. Here’s what we’ve covered:

• CRS presents with a spectrum of symptoms, primarily affecting the lower spine, limbs, and pelvic organs.
• Types range from mild partial sacral agenesis to severe forms like sirenomelia, with unique challenges at each end of the spectrum.
• Causes include maternal diabetes, genetic factors, teratogenic exposures (like retinoic acid), and possibly vascular disruptions, though many cases remain idiopathic.
• Treatment is multidisciplinary, focusing on surgical correction, rehabilitation, and long-term management of neurogenic bladder and bowel issues.

Key Takeaways:

• Early diagnosis and individualized care are essential for optimizing outcomes.
• Ongoing research into genetic and embryological mechanisms is crucial for future prevention and therapies.
• With comprehensive support, many individuals with CRS can lead fulfilling lives.

By understanding the facets of Caudal Regression Syndrome, families and care teams can better support those affected on their journey toward health and independence.