Introduction

Caudal regression syndrome (CRS) is a rare congenital condition that disrupts the development of the lower spine and surrounding structures during early gestation. The sacrum (located at the base of the spine), the spinal cord, the legs, and, sometimes, internal organs, such as the bladder, kidneys, intestines, and genitals, may be affected.¹

Understanding how common CRS is matters because it can facilitate earlier diagnosis, improved care, and more effective planning and support for affected families. Recognising who is most at risk also helps guide prevention efforts and improves outcomes over time. However, inconsistent diagnostic criteria and under-reporting make it challenging to determine the true frequency of the condition.¹

What is Caudal Regression Syndrome (CRS)?

CRS is a disorder of fetal development that primarily affects the lower (caudal) spine. In some cases, parts of the lower spine are misshapen, underdeveloped, or completely absent, a condition sometimes referred to as sacral agenesis. The spinal cord may also be malformed or tethered, which can disrupt nerve functions in the lower body.¹

These anatomical changes can lead to a wide range of complications:¹

• Reduced mobility or joint deformities
• Clubfoot or difference in leg length
• Issues with bladder or bowel control
• Abnormalities in kidney or genital development
• Changes in skin sensation or reflexes

The severity of CRS can vary widely, and while some children can walk independently, others require mobility aids or surgical interventions to manage symptoms.¹

How often does it occur?

CRS is considered extremely rare, with most large-scale studies estimating an incidence of approximately 1 in 25,000 to 60,000 live births, depending on the definition of cases. This estimate is primarily drawn from hospital-based records and neonatal case series in North America and Europe.¹

Broader epidemiological reviews cite an incidence of approximately 1 to 5 cases per 100,000 live births, reflecting variability in how the syndrome is diagnosed and recorded. The condition lies on a spectrum and may overlap with related disorders:^1,2

• Sirenomelia
• Currarino syndrome
• Sacral agenesis

In some studies, these overlapping conditions are grouped under CRS, while in others they are excluded. This inconsistency makes direct comparisons difficult. Despite its rarity, CRS has serious health implications and can affect multiple organ systems. Even mild cases may require long-term support and medical monitoring.^1,2,3

Where is it most common?

There is currently no clear evidence that CRS is more common in one part of the world than another.⁴ However, the majority of published cases come from high-income countries with robust healthcare systems and data reporting.⁵ In many low- and middle-income countries (LMICs), access to prenatal imaging and specialist paediatric care is limited. This lack of resources means that milder forms of CRS often go undiagnosed, and cases may be under-reported.⁶

Even in high-resource settings, milder forms of CRS may go undetected or be misattributed to more common orthopaedic or urological conditions. This diagnostic ambiguity can result in a significant underestimation of the actual global prevalence.^1,2

Who is most at risk?

Recent case reviews have found no consistent sex-based difference in the presence of CSR. Although it can occur in any pregnancy, infants born to mothers with pre-existing diabetes (Type 1 or Type 2) face a significantly higher risk. Studies estimate that between 15 to 25% CRS cases are associated with maternal diabetes mellitus, indicating a strong birth defect-causing effect associated with poor control of blood glucose during pregnancy.^1,7,8

It is thought that elevated blood glucose levels during the first month of gestation, especially between days 14 and 23, when the neural tube (the structure that later forms the brain and spinal cord) and caudal mesoderm (a critical embryonic tissue layer) form, can interfere with the normal development of the lower spinal structures.^1,9

Causes and contributing factors

The exact cause of CRS remains unclear. Researchers believe that it is a multifactorial condition, resulting from a combination of genetic and environmental influences. In many cases, CRS appears to occur sporadically, with no identifiable cause, suggesting that a range of different risk factors may interact to trigger the condition.^1,2

Environmental factors

Beyond maternal diabetes, researchers have proposed several other environmental influences that contribute to CRS.^4,9 

• Hypoxia (low oxygen levels) – disrupts normal tissue development
• Amino acid imbalance in early gestation
• Exposure to substances like alcohol, retinoic acid, or organic solvents
• Abnormal blood flow to the lower body (vascular disruption hypothesis) – a misdirected or malformed abdominal artery may limit blood supply to the caudal region

Genetic factors

In rare cases, mutations in certain genes have been linked to the condition.

• VANGL1 – the exact role this gene variant plays in the development is unknown. It is inherited in an autosomal dominant pattern¹⁰
• MNX1 (HLXB9) – associated with Currarino syndrome, which shares overlapping features with CRS, such as partial sacral agenesis and anorectal malformations¹¹

How is it diagnosed?

CRS may be diagnosed before or after birth, depending on its severity. In many cases, signs of abnormal spinal development can be seen during a routine prenatal ultrasound, particularly around weeks 16 to 22. In some cases, a fetal MRI may be used to provide more detailed images of the spine and internal organs.^12,13,14

After birth, the diagnosis may be based on physical signs, such as missing portions of the lower spine, leg abnormalities, or bladder/bowel dysfunction. Doctors usually confirm the diagnosis using imaging tests to assess the spinal and surrounding structures. Early diagnosis is important for planning treatment and support, but it is not always straightforward, especially when symptoms are subtle.^1,2,12

FAQs

Can CRS be prevented?

No, because some of the causes are the result of random genetic changes that cannot be predicted or prevented. However, steps can be taken to reduce the risks by working with a healthcare provider to manage blood glucose levels if the pregnant individual has diabetes.

Can CRS be seen on every ultrasound?

Not always. Many cases are detected during routine scans, but milder forms may be overlooked or mistaken for other conditions. Additional imaging, like fetal MRI, can improve detection.

Are there treatments for CRS?

There’s no cure, but treatment focuses on managing symptoms and improving quality of life. Options may include surgery, physical therapy, mobility aids, and support for bladder/bowel function.

Does CRS worsen over time?

The structural changes to the spine and nerves occur before birth and don’t progress after birth. However, secondary complications, such as joint deformities or urinary tract infection, can develop over time without proper management.

Does CRS affect life expectancy?

It depends on the severity and whether vital organs are affected. Many individuals with mild CRS live a normal lifespan, while severe cases involving major organ malformations may have a higher risk of complications early in life.

Does CRS run in families?

Most cases occur sporadically, but rarely can they be linked to inherited genetic variants. If there’s a family history of similar conditions, genetic counselling is recommended.

Is CRS linked to other congenital syndromes?

Yes, CRS can overlap with or occur alongside conditions such as Currarino syndrome or sirenomelia, which share certain features but have different causes and diagnostic criteria.

Summary

CRS is a rare birth condition affecting the lower spine and surrounding organs during early pregnancy. Symptoms can range from mild mobility differences to severe organ malformations. One of the strongest known risk factors is maternal diabetes, which can increase the likelihood of CRS, particularly when blood glucose is poorly controlled during early pregnancy.

CRS occurs worldwide, but its true prevalence is likely underestimated due to missed or delayed diagnoses, especially in areas with limited prenatal screening. The causes of CRS are thought to be multifactorial, involving both genetic mutations and environmental influences.

While there is no cure, early diagnosis, before or after birth, allows for personalised medical, surgical and supportive care that can greatly improve long-term health and quality of life. Raising awareness among healthcare providers and families is essential for prompt detection, effective management, and better outcomes.