Caudal regression syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Caudal regression syndrome is a disorder that impacts the development of the lower (caudal) part of the spine. The condition can affect many parts of the lower body, including the lower back and limbs, the genitourinary tract, and the gastrointestinal tract.

In people with this disorder, the bones of the lower spine (vertebrae) are misshapen or missing. The end of the spinal cord, the bundle of nerves and cells protected by the vertebrae, may also be malformed or missing. Sometimes, the spinal cord is abnormally connected (tethered) to nearby tissues. People with caudal regression syndrome can also have an abnormal curvature of the spine (lordosis or kyphosis). The spinal abnormalities may affect the size and shape of the chest, which very rarely leads to breathing problems.

Individuals with caudal regression syndrome may have small hip bones. The buttocks tend to be flat and dimpled. The bones of the legs are typically underdeveloped, and the joints in the lower limbs may be unusually stiff and difficult to move. In some affected individuals, the legs are bent with the knees pointing out to the side and the feet tucked underneath the hips (sometimes called a frog leg-like position). These individuals may have webbed skin behind their knees. In other affected individuals, the knees may not bend, and the legs remain in a straight position. Their feet may be inward- and upward-turning (clubfeet) or outward- and upward-turning (calcaneovalgus). Some people with caudal regression syndrome have reduced or excessive sensation in their lower limbs. Sensitivity differs from person to person and from one area of the limb to another.

Mobility in people with caudal regression syndrome is varied. Some individuals with the condition walk independently, and others require mobility aids, such as braces, crutches, walkers, or wheelchairs.

Abnormalities in the genitourinary tract in people with caudal regression syndrome are diverse. Urinary tract problems can result from abnormalities in the lowest part of the spinal cord, which contains the nerves that control bladder function. Damage to these nerves can cause a condition called neurogenic bladder, which makes it difficult to control the flow of urine. In addition, the kidneys may be malformed in people with caudal regression syndrome; defects include a missing kidney (unilateral renal agenesis), kidneys that are fused together (horseshoe kidney), or duplication of the tubes that carry urine from each kidney to the bladder (ureteral duplication). These kidney abnormalities and neurogenic bladder can lead to frequent urinary tract infections and the backflow (reflux) of urine into the kidneys, which damage the kidneys and can cause progressive kidney failure.

Genital abnormalities in people with caudal regression syndrome can include the urethra opening on the underside of the penis (hypospadias) or undescended testes (cryptorchidism). Some affected people may have an abnormal connection between the rectum and vagina (rectovaginal fistula). In severe cases, people with this condition may have underdeveloped genitalia (genital agenesis).

People with caudal regression syndrome may have abnormal twisting (malrotation) of the large intestine, an obstruction of the anal opening (imperforate anus), soft out-pouchings in the lower abdomen (inguinal hernias), or other malformations of the gastrointestinal tract. Affected individuals are often constipated and may have difficulty with bowel control.

The upper part of the body can also be affected. Some people with caudal regression syndrome have a heart condition or hearing problems.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Caudal regression syndrome is a complex condition that may have different causes in different people. The condition is likely caused by the interaction of multiple genetic and environmental factors. One risk factor for the development of caudal regression syndrome is the presence of diabetes during pregnancy. It is thought that increased blood sugar (glucose) levels and other metabolic problems related to diabetes may have a harmful effect on a developing fetus, increasing the likelihood of developing caudal regression syndrome. The risks to the fetus are further increased if the diabetes is poorly managed. Researchers are trying to identify other factors that contribute to the development of this complex disorder.

Some researchers believe that a disruption of fetal development around day 28 of pregnancy causes caudal regression syndrome. The developmental problem is thought to affect the middle layer of embryonic tissue known as the mesoderm. Disruption of normal mesoderm development impairs normal formation of parts of the skeleton, gastrointestinal system, and genitourinary system.

Other researchers think that caudal regression syndrome is caused by the presence of an abnormal artery in the abdomen, which diverts blood flow away from the lower areas of the developing fetus. Decreased blood flow to these areas is thought to interfere with their development and lead to the signs and symptoms of caudal regression syndrome.

Some scientists believe that the abnormal development of the mesoderm reduces the blood flow, while other scientists believe that the reduced blood flow causes the abnormal mesoderm development. Many scientists think that the cause of caudal regression syndrome is a combination of abnormal mesoderm development and decreased blood flow to the caudal areas of the fetus.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Caudal regression syndrome occurs sporadically, which means it occurs in people with no history of the condition in their family. Multiple genetic and environmental factors likely affect the risk of developing this condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The frequency of caudal regression syndrome is unknown. It is estimated to occur in 1 to 2.5 in 100,000 newborns. This condition is much more common among infants whose parent has diabetes while pregnant, affecting an estimated 1 in 350 newborns in this group.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of pelvic girdle bone morphology · Very frequent (99-80%)

An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.

Abnormality of the wing of the ilium · Very frequent (99-80%)

An anomaly of the ilium ala. This is the large expanded portion of the ilum which bounds the greater pelvis laterally.

Aplasia/Hypoplasia of the sacrum · Very frequent (99-80%)

Aplasia or developmental hypoplasia of the sacral bone.

Bowel incontinence · Very frequent (99-80%)

Involuntary fecal soiling in adults and children who have usually already been toilet trained.

Impulsivity · Very frequent (99-80%)

Acting on the spur of the moment or on a momentary basis without consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in behavior that is uninhibited, cannot be inhibited, and is uncontrolled. The possibility of repression is inconceivable.

Maternal diabetes · Very frequent (99-80%)

Maternal diabetes can either be a gestational, mostly type 2 diabetes, or a type 1 diabetes. Essential is the resulting maternal hyperglycemia as a non-specific teratogen, imposing the same risk of congenital malformations to pregnant women with both type 1 and type2 diabetes.

Abnormal vertebral segmentation and fusion · Very frequent (99-80%)

Decreased muscle mass · Very frequent (99-80%)

Other findings in the same source

From: Orphanet

Additional reported features include Hypoplastic vertebral bodies (Very frequent (99-80%)); Abnormal cardiovascular system morphology (Frequent (79-30%)); Abnormality of the ureter (Frequent (79-30%)); Anal atresia (Frequent (79-30%)); Ectopic kidney (Frequent (79-30%)); Joint stiffness (Frequent (79-30%)); Reduced tendon reflexes (Frequent (79-30%)); Renal agenesis (Frequent (79-30%)); Scoliosis (Frequent (79-30%)); Talipes equinovarus (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Caudal regression syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Caudal regression syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.