Prune Belly Syndrome: Symptoms, Types, Causes and Treatment

Prune Belly Syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare and complex congenital disorder, most commonly affecting males. Its name comes from the characteristic wrinkled appearance of the abdomen, which resembles a dried prune. Understanding this syndrome requires a close look at its distinctive symptoms, varying types, unclear but intriguing causes, and the evolving landscape of treatment. This article provides a comprehensive exploration, drawing upon current research and real-world clinical experience.

Symptoms of Prune Belly Syndrome

Prune Belly Syndrome is defined by a classic triad of symptoms, but its impact often extends beyond these core features. Early recognition of these symptoms is crucial for prompt management and improved outcomes.

Core	Description	Additional Effects	Sources
Abdominal	Lax, wrinkled, thin abdominal wall	Easy palpation of organs, visible bulge	1 3 4 5
Urinary	Urinary tract malformations (e.g., mega-bladder, hydronephrosis, mega-ureter)	Urinary retention, infections, renal failure	1 2 3 4 5 6 8
Genital	Bilateral undescended testes (cryptorchidism)	Infertility, risk of testicular cancer	1 2 3 4 5 11
Other	Associated anomalies (respiratory, skeletal, cardiac)	Scoliosis, dextrocardia, pulmonary distress	3 4 5 6

Table 1: Key Symptoms of Prune Belly Syndrome

The Classic Triad: Abdominal, Urinary, Genital

• Abdominal wall deficiency: The hallmark feature is a thin, wrinkled, and flaccid abdominal wall that can balloon outwards, allowing easy palpation of underlying organs. This gives the abdomen its distinctive prune-like appearance. The muscle deficiency is often so severe that the skin alone covers the abdominal contents, making the area appear sunken or excessively lax 1 3 4 5.
• Urinary tract malformations: These can include a massively enlarged bladder (mega-bladder), dilated ureters (mega-ureter), and hydronephrosis (swelling of the kidneys due to urine buildup). The severity varies, but these malformations can lead to urinary retention, recurrent infections, and progressive kidney damage 1 2 3 4 5 6 8.
• Bilateral cryptorchidism: In most cases, both testicles fail to descend into the scrotum. This not only raises the risk of infertility but also increases the likelihood of testicular cancer later in life 1 2 3 4 5 11.

Associated and Systemic Manifestations

Prune Belly Syndrome can also present with a range of systemic issues:

• Respiratory distress: Pulmonary hypoplasia (underdeveloped lungs) may occur, especially in severe cases, contributing to early neonatal mortality 3 4 5.
• Skeletal anomalies: Scoliosis and other vertebral malformations are documented, as well as limb and joint abnormalities 5 6.
• Cardiac anomalies: Dextrocardia (heart on the right side) and other congenital heart problems have been reported 5.
• Other genitourinary anomalies: Malformations of the prostate and urethra can further complicate the clinical picture 1.

Clinical Course and Prognosis

• The severity of symptoms can range from mild, with near-normal function, to life-threatening, particularly when severe kidney or lung issues are present 2 3 4 8.
• Many infants with severe forms may be stillborn or die shortly after birth; those who survive may face chronic kidney disease, urinary incontinence, and challenges with fertility 6 8.

Types of Prune Belly Syndrome

While PBS is defined by its core triad, its expression varies widely, leading to different clinical classifications or "types." Understanding these variations is crucial for tailoring management and anticipating outcomes.

Type	Description	Key Features	Sources
Classic	Full triad present	Abdominal, urinary, genital anomalies	1 3 4
Incomplete	Missing one or more triad features	Partial muscle deficiency or unilateral cryptorchidism	2 6
Syndromic	PBS plus other anomalies	Cardiac, skeletal, or multisystem defects	3 5 6 10

Table 2: Types of Prune Belly Syndrome

Classic Type

• Definition: This is the textbook version, presenting with the full triad: severe abdominal wall deficiency, urinary tract dilation/malformations, and bilateral undescended testes 1 3 4.
• Clinical course: Often the most severe, frequently requiring multiple surgeries and ongoing management for renal and respiratory issues.

Incomplete Type

• Definition: Not all three hallmark features are present. For example, a patient may have abdominal wall deficiency and urinary tract abnormalities without cryptorchidism, or the muscle deficiency may be less pronounced 2 6.
• Clinical course: These cases can be less severe, sometimes discovered later in childhood due to milder symptoms.

Syndromic or Associated Type

• Definition: PBS occurs alongside other congenital anomalies, such as cardiac defects, skeletal malformations, or part of a broader genetic syndrome 3 5 6 10.
• Clinical course: These patients often require more complex care, and prognosis depends on the severity of associated conditions.

Clinical Variability

• Severity spectrum: Some individuals may have mild forms and retain near-normal kidney and bladder function, while others face life-threatening organ failure 2 3 4 6.
• Gender differences: While PBS predominantly affects males (about 95% of cases), rare female cases have been reported, often with different presentations and outcomes 6.

Causes of Prune Belly Syndrome

The underlying causes of PBS are still not fully understood, but research points to a mix of genetic, developmental, and possibly environmental factors.

Factor	Description	Evidence	Sources
Genetic	Mutations in genes (e.g., PIEZO1, FLNA)	Familial cases, gene studies	9 10
Developmental	Fetal urinary tract obstruction	Early bladder distention, abdominal muscle stretching	7
Environmental	Unknown/non-genetic contributors	Lack of consistent inheritance	4 7 8

Table 3: Proposed Causes of Prune Belly Syndrome

Genetic Contributions

• PIEZO1 mutations: Recent research has identified loss-of-function mutations in the PIEZO1 gene, which codes for a mechanosensitive ion channel involved in urinary tract development. These mutations may impair normal bladder function and abdominal muscle development. Notably, in vitro studies suggest that pharmacological activation of PIEZO1 could help rescue some of these defects, pointing to new treatment avenues 9.
• Filamin A (FLNA) mutations: Hemizygous mutations in the X-linked FLNA gene have been found in some PBS cases, particularly in males who survive into adulthood. FLNA is crucial for smooth muscle cell structure and function, supporting the theory that muscle and urinary tract defects are interlinked 10.
• Familial cases: While most PBS cases are sporadic, rare familial clusters suggest a possible hereditary component in some instances 9 10.

Developmental Theories

• Urethral obstruction malformation complex: One prominent theory posits that early fetal urinary tract obstruction (often due to urethral blockage) leads to chronic bladder distention. The resulting increased intra-abdominal pressure stretches and thins the developing abdominal wall, causing muscle deficiency. This mechanism also explains the male predominance, as males are more prone to congenital urethral obstructions 7.
• Variability in severity: The extent and timing of the obstruction may account for the wide range of clinical presentations, from mild to lethal 7.

Environmental and Multifactorial Aspects

• Non-genetic influences: No single environmental or maternal factor has been consistently linked to PBS. The lack of a clear inheritance pattern in most cases suggests a multifactorial origin, possibly involving both genetic susceptibility and developmental events 4 7 8.
• Unknowns remain: Despite recent genetic discoveries, the cause remains unidentified in the majority of cases. Ongoing research is focused on uncovering additional genetic and environmental contributions.

Treatment of Prune Belly Syndrome

Management of PBS is highly individualized, reflecting the variable severity and multi-system involvement. Advances in surgical techniques and supportive care have significantly improved outcomes for many children with this syndrome.

Approach	Purpose	Outcome/Notes	Sources
Supportive	Stabilize fluids, treat infections	Essential in newborns, improves survival	4 5
Surgical	Correct anatomical defects	Abdominoplasty, urinary tract reconstruction, orchiopexy	1 2 5 11 12
Renal	Manage kidney dysfunction	Dialysis, transplant if needed	1 6 11
Long-term	Monitor and manage complications	UTI prevention, fertility support	1 3 6 11 12

Table 4: Treatment Approaches for Prune Belly Syndrome

Supportive Care in the Neonatal Period

• Immediate priorities: In newborns, stabilizing respiratory function, maintaining fluid and electrolyte balance, and treating infections (especially urinary tract infections and sepsis) are top priorities 4 5.
• Urinary drainage: When urinary obstruction is present, urgent surgical interventions such as vesicostomy may be needed to relieve pressure and preserve kidney function 2 5.

Surgical Management

• Abdominal wall repair (abdominoplasty): This surgery aims to strengthen the abdominal wall, improve appearance, and facilitate breathing and organ function. Most patients benefit from this intervention, with marked improvement in abdominal tone and contour 1 11 12.
• Urinary tract reconstruction: Procedures may include reimplantation of ureters, correction of bladder abnormalities, and, in severe cases, removal of non-functioning kidneys. The goal is to restore urinary flow, prevent infections, and preserve kidney function 1 2 11 12.
• Orchiopexy: Surgical placement of undescended testes into the scrotum is performed to reduce the risk of malignancy and support fertility. This is considered mandatory and often performed in combination with other surgeries 1 11 12.
• Comprehensive, individualized approach: Some centers perform all necessary surgeries in a single session, while others stage procedures based on the child’s health and needs 11 12.

Renal Management

• Monitoring and intervention: Regular assessment of kidney function is essential. Progressive renal deterioration is the leading cause of long-term mortality, especially among males 1 6 11.
• Advanced therapies: In patients who develop end-stage renal disease, dialysis and eventually kidney transplantation may be required 1 6 11.

Long-term and Multidisciplinary Care

• Prevention of urinary tract infections: Ongoing monitoring, prophylactic antibiotics, and clean intermittent catheterization may be necessary for some children.
• Fertility and hormonal support: Early intervention for cryptorchidism and hormonal evaluation during adolescence are important for optimizing fertility potential 3 11.
• Quality of life: With early, comprehensive care, many patients report good physical and mental health outcomes, even when facing significant anatomical challenges 2 11 12.

Challenges in Resource-Limited Settings

• Limited access: In some regions, lack of specialized pediatric surgical and urology services, as well as advanced imaging, can hinder optimal care 4 6.
• Adapted approaches: Supportive care and basic surgical interventions may still lead to meaningful improvements, but outcomes are generally better with full access to multidisciplinary teams 4 6.

Conclusion

Prune Belly Syndrome is a rare but serious congenital disorder with a broad spectrum of severity. Early recognition and a tailored, multidisciplinary approach are essential to optimize outcomes for affected children.

Key Points:

• Triad of symptoms: Abdominal wall deficiency, urinary tract malformations, and bilateral undescended testes are the diagnostic cornerstones 1 3 4.
• Wide variability: PBS ranges from mild to life-threatening, with associated anomalies often influencing prognosis 2 3 6.
• Genetic and developmental causes: Recent research highlights roles for PIEZO1 and FLNA mutations, as well as the impact of fetal urinary tract obstruction 7 9 10.
• Surgical advances: Comprehensive surgical management, including abdominoplasty, urinary tract reconstruction, and orchiopexy, can significantly improve quality of life and survival 1 11 12.
• Renal care is crucial: Kidney function monitoring and intervention remain central to long-term success 1 6 11.
• Resource challenges: Early diagnosis and specialized care are vital, but even basic supportive measures can make a difference where resources are limited 4 6.

PBS remains a challenging condition, but with ongoing research and a patient-centered approach, outcomes continue to improve.