Pentalogy of Cantrell is a rare and complex congenital syndrome, present at birth, involving multiple midline birth defects. It occurs with varying degrees of severity, potentially leading to severe complications. The syndrome affects approximately 1 in 65,000 to 200,000 live births globally.
The Five Core Defects
Pentalogy of Cantrell is defined by five specific malformations affecting the chest and abdominal regions. These defects vary in severity, contributing to the condition’s diverse presentation.
A characteristic defect is an abnormality of the lower breastbone, or sternum. This can range from a small cleft or shortened sternum to its complete absence. Such sternal defects can leave the underlying heart less protected.
A defect in the abdominal wall often presents as an omphalocele, where abdominal organs like intestines or liver protrude outside the body through the belly button.
The syndrome includes a defect in the diaphragm, the muscle separating the chest and abdominal cavities that assists with breathing. This defect, often an anterior diaphragmatic hernia, allows abdominal contents to push into the chest, hindering lung development and function.
A defect in the sac surrounding the heart, known as the pericardium, is also a component. This involves a deficiency in the diaphragmatic pericardium, exposing the heart and making it vulnerable to injury or displacement.
The fifth defect involves the heart itself, most notably its abnormal location outside the chest cavity, called ectopia cordis. The heart may be partially or completely displaced. Various intracardiac malformations, such as ventricular septal defects (holes between the heart’s lower chambers), atrial septal defects, or Tetralogy of Fallot, are frequently observed alongside these structural issues.
Suspected Causes and Development
The exact cause of Pentalogy of Cantrell remains unknown, with most cases occurring sporadically without a clear pattern of inheritance. Current understanding suggests the condition arises from an error during the very early stages of fetal development, specifically between 14 and 18 days after conception. This developmental failure involves the lateral mesodermal folds.
A prevailing theory posits that the defects stem from abnormal development of the septum transversum, which contributes to the diaphragm, and a failure of the somatic and splanchnic mesoderm to properly migrate and fuse along the body’s midline. This disruption prevents the normal closure of the chest and abdominal walls, leading to the characteristic anomalies. While most cases are sporadic, rare familial instances and associations with chromosomal abnormalities like Trisomy 13, 18, and 21 suggest a possible genetic influence.
Diagnosis Before and After Birth
Diagnosis of Pentalogy of Cantrell can occur both before and after birth. Prenatal diagnosis often begins with routine ultrasound examinations, which can detect characteristic defects as early as 10 to 13 weeks of gestation. The presence of both ectopia cordis (heart outside the chest) and an abdominal wall defect like an omphalocele should raise suspicion.
Elevated levels of maternal serum alpha-fetoprotein (MSAFP) can also serve as an indicator during prenatal screening, as these levels are often associated with abdominal wall defects. Detailed imaging, including advanced 3D sonography and fetal echocardiograms, provides a clearer understanding of the anatomical conditions and the extent of heart involvement. If a diagnosis is made prenatally, chromosomal analysis may be recommended to check for associated genetic abnormalities.
After birth, diagnosis is typically confirmed through a physical examination of the newborn, where the visible sternal and abdominal wall defects, along with any external heart displacement, are apparent. Subsequent imaging studies are then performed to fully assess the internal defects and their severity. These include X-rays to visualize skeletal and diaphragmatic anomalies, CT scans to evaluate thoracic contour and organ positioning, and echocardiograms to comprehensively assess intracardiac malformations and heart function.
Surgical Management Approaches
Management of Pentalogy of Cantrell primarily involves complex surgical interventions, often requiring a multidisciplinary team of specialists including cardiac surgeons, general surgeons, and neonatologists. The specific approach is tailored to the individual patient, considering the type and extent of their defects. A common strategy involves a “staged repair,” where multiple surgeries are performed over time rather than a single procedure.
The immediate goals of surgery often include covering any exposed organs, such as the heart or abdominal contents, to prevent infection and further injury. Subsequent operations focus on repositioning the heart back into the chest cavity, which can be challenging due to the potentially small thoracic space. Surgeons also work to repair the defects in the abdominal wall, reconstruct the sternum, and close any openings in the diaphragm. Advanced reconstructive techniques, including the use of tissue flaps or biomaterials, may be employed to achieve successful closure of these complex defects.
Prognosis and Variability of the Condition
The outlook for individuals with Pentalogy of Cantrell is highly variable, largely dependent on the severity of malformations, particularly those affecting the heart. The most significant factor influencing prognosis is the presence and complexity of ectopia cordis. Patients with severe ectopia cordis generally face a poorer prognosis, and survival rates can be low, with many succumbing in the early days of life even with surgical intervention.
The condition is often classified into “complete” and “incomplete” forms, which helps in predicting outcomes. Complete Pentalogy of Cantrell involves the presence of all five characteristic defects, including severe intracardiac anomalies and ectopia cordis, and is associated with a higher mortality rate. In contrast, infants with an incomplete form, who may lack one or more of the five defects or have less severe presentations, generally have a more favorable prognosis and improved chances of survival after surgical repair. Associated anomalies, such as those affecting the central nervous system, face, or limbs, can also impact the overall outcome.