Cerebral palsy (CP) is a group of permanent disorders affecting a person’s ability to move, maintain posture, and balance. This condition results from a non-progressive disturbance occurring in the developing fetal or infant brain. While CP was historically attributed almost exclusively to acquired factors like birth injury, modern research confirms that genetic factors play a significant, complex role in the cause and susceptibility for a substantial subset of cases. This recognition has led to a more nuanced view of CP’s origins, often involving a mix of environmental and hereditary influences.
Cerebral Palsy: Defining the Primary Causes
The majority of cerebral palsy cases result from acquired brain injury occurring before, during, or shortly after birth. The most significant risk factor is premature birth, particularly for infants born before 32 weeks of gestation or those with a very low birth weight (less than 1,500 grams). These infants are prone to periventricular leukomalacia (PVL), which is damage to the brain’s white matter.
Another common acquired cause involves a lack of oxygen or blood flow to the brain, medically termed asphyxia or hypoxia. This event can occur due to complications during labor and delivery, such as placental abruption or issues with the umbilical cord. Maternal infections, including rubella, cytomegalovirus, or chorioamnionitis, can also heighten the risk by triggering an inflammatory response that indirectly damages the fetal brain. Acquired CP occurring after the first 28 days of life accounts for up to 10% of cases, often resulting from severe head trauma or infections like bacterial meningitis.
When Genetics Are Involved
Genetic factors contribute to CP in several distinct ways, accounting for up to one-third of all cases. In some instances, CP is the direct result of a single-gene mutation, representing a highly penetrant, monogenic cause. These mutations are often found in genes that regulate early brain development and may be associated with syndromes where CP-like symptoms are prominent.
Structural changes in the DNA, known as Copy Number Variations (CNVs), also play a role. CNVs involve the deletion or duplication of large segments of genetic material. They are identified in approximately 7% to 10% of unexplained CP cases and are often de novo, meaning they arise spontaneously and are not inherited from either parent.
Most commonly, genetics contributes through genetic susceptibility. This involves common variations across multiple genes that individually have a small effect on risk. These polygenic risk factors do not directly cause CP but instead lower the threshold at which environmental insults, such as prematurity or infection, cause permanent brain injury.
Evaluating Risk and Determining Cause
A comprehensive diagnostic evaluation is necessary to distinguish between acquired and genetic causes of CP. Neuroimaging, specifically Magnetic Resonance Imaging (MRI), is standard, helping clinicians identify the location and type of brain injury. The MRI appearance can suggest a genetic cause if it points to a structural abnormality rather than an acquired event. Genetic testing, such as Whole Exome Sequencing (WES), is increasingly used, especially when a clear environmental cause is absent or when CP is accompanied by other neurological features.
The discovery of a genetic cause has significant implications for family planning, making genetic counseling an important step. For families whose child’s CP is purely acquired, the risk of recurrence in a future pregnancy is low, estimated at 1% to 2%. If genetic testing identifies a hereditary mutation, the recurrence risk can be much higher, potentially reaching 25% or 50% depending on the mode of inheritance. If the genetic cause is a de novo mutation, the risk for future children remains low, similar to the general population.