In some cases, the defect is linked to mutations of the EMX2, SIX3, and Collagen, type IV, alpha 1 genes. Because having a sibling with schizencephaly has been statistically shown to increase risk of the disorder, it is possible that there is a heritable genetic component to the disease.

In utero exposure to cocaine and other street drugs can lead to porencephaly.

In utero exposure to cocaine and other street drugs can lead to schizencephaly.

In utero exposure to cocaine and other street drugs can lead to hydranencephaly.

From recent studies, de novo and inherited mutations in the gene "COL4A1", suggesting genetic predisposition within the family, that encodes type IV collagen α1 chain has shown to be associated with and present in patients with porencephaly. "COL4A1" mutation causes a variety of phenotypes, including porencephaly, infantile hemiplegia, and cerebral small vessel diseases involving both stroke and infarction. Abnormal gene expression of "COL4A1" can contribute to the development of porencephaly. "COL4A1" gene expresses a type IV collagen (basement protein) that is present in all tissue and blood vessels and is extremely important for the structural stability of vascular basement membranes. The "COL4A1" protein provides a strong layer around blood vessels. The mutation can weaken the blood vessels within the brain, elevating the probability of a hemorrhage, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. In a mouse model, mouse with "COL4A1" mutations displayed cerebral hemorrhage, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. Purposely causing a mutation in the "COL4A1" gene caused several mouse to develop cerebral hemorrhage and porencephaly-like diseases. Though, there is no direct correlation between mutations of the "COL4A1" gene, it appears that it has an influential effect on the development of porencephaly.

Another genetic mutation, "factor V G1691A" mutation, has been reported to show possible association to the development of porencephaly. A mutation in "factor V G1691A" increases the risk of thrombosis, blood clots, in neonates, infants, and children. Therefore, 76 porencephalic and 76 healthy infants were investigated for "factor V G1691A" mutation along with other different prothrombotic risk factors. The results indicated that there was higher prevalence of the "factor V G1691A" mutation in the porencephalic patient group. The prediction that childhood porencephaly is caused by hypercoagulable state, a condition where one has a higher chance of developing blood clots, was supported by the significance of the "factor V G1691A" mutation. Also, pregnant women in hypercoagulable state can cause the fetus to have the same risks, therefore possibly causing fetal loss, brain damage, lesions, and infections that lead to porencephaly. However, other different prothrombotic risk factors individually did not reach statistical significance to link it to the development of porencephaly, but a combination of multiple prothrombotic risk factors in the porencephaly group was significant. Overall, "factor V G1691A" mutation has been linked to the development of porencephaly. However, this one mutation is not the cause of porencephaly, and whether further prothrombiotic risk factors are associated with porencephaly still remains unknown.

As a recessive genetic condition, both parents must carry the asymptomatic gene and pass it along to their child, a chance of 25 percent. Despite determination of cause, hydranencephaly afflicts both males and females in equal numbers.

In the developing brain, neural stem cells must migrate from the areas where they are born to the areas where they will settle into their proper neural circuits. Neuronal migration, which occurs as early as the second month of gestation, is controlled by a complex assortment of chemical guides and signals. When these signals are absent or incorrect, neurons do not end up where they belong. This can result in structurally abnormal or missing areas of the brain in the cerebral hemispheres, cerebellum, brainstem, or hippocampus.

Several genetic abnormalities in children with NMDs have been identified. Defects in genes that are involved in neuronal migration have been associated with NMDs, but the role they play in the development of these disorders is not yet well understood.

A study in Sweden investigated the impact of environmental factors on NMDs. The study indicated that there might be an impact of low or subnormal maternal BMI before and during pregnancy, maternal infection, such as rubella, and maternal smoking on fetal brain development, including neuronal migration. The roles of maternal BMI and congenital infections should be tested in future analytical studies.

NMDs occur in the instance that 1) neuroblasts do not migrate from all of the ventricles or migrate only part of the way, 2) only some of the neuroblasts reach the cortical layer, 3) neuroblasts overshoot the appropriate cortical layer and protrude into the subarachnoid space, or 4) the late stage organization of the neuronal layer in the cortex is disrupted. Abnormal migration ultimately results in abnormal gyral formation.

Neuronal migration disorder (NMD) refers to a heterogenous group of disorders that, it is supposed, share the same etiopathological mechanism: a variable degree of disruption in the migration of neuroblasts during neurogenesis. The neuronal migration disorders are cerebral dysgenesis, brain malformations caused by primary alterations during neurogenesis; on the other hand, brain malformations are highly diverse and refer to any insult to the brain during its formation and maturation due to intrinsic or extrinsic causes that ultimately will alter the normal brain anatomy. However, there is some controversy in the terminology because virtually any malformation will involve neuroblast migration, either primarily or secondarily.

Cephalic disorders (from the Greek word "κεφάλι", meaning "head") are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. Cephalic means "head" or "head end of the body."

Cephalic disorders are not necessarily caused by a single factor, but may be influenced by hereditary or genetic conditions, nutritional deficiencies, or by environmental exposures during pregnancy, such as medication taken by the mother, maternal infection, or exposure to radiation. Some cephalic disorders occur when the cranial sutures (the fibrous joints that connect the bones of the skull) join prematurely. Most cephalic disorders are caused by a disturbance that occurs very early in the development of the fetal nervous system.

The human nervous system develops from a small, specialized plate of cells on the surface of the embryo. Early in development, this plate of cells forms the neural tube, a narrow sheath that closes between the third and fourth weeks of pregnancy to form the brain and spinal cord of the embryo. Four main processes are responsible for the development of the nervous system: cell proliferation, the process in which nerve cells divide to form new generations of cells; cell migration, the process in which nerve cells move from their place of origin to the place where they will remain for life; cell differentiation, the process during which cells acquire individual characteristics; and cell death, a natural process in which cells die.

Damage to the developing nervous system is a major cause of chronic, disabling disorders and, sometimes, death in infants, children, and even adults. The degree to which damage to the developing nervous system harms the mind and body varies enormously. Many disabilities are mild enough to allow those afflicted to eventually function independently in society. Others are not. Some infants, children, and adults die, others remain totally disabled, and an even larger population is partially disabled, functioning well below normal capacity throughout life.

The National Institute of Neurological Disorders and Stroke (NINDS) is currently "conducting and supporting research on normal and abnormal brain and nervous system development."

Autosomal dominant porencephaly type I is a rare type of porencephaly that causes cysts to grow on the brain and damage to small blood vessels, which can lead to cognitive impairment, migraines, seizures, and hemiplegia or hemiparesis.

Different people are affected very differently by this disease. The main manifestation is fluid-filled cysts that grow on the brain and can cause damage that varies depending on their location and severity. Symptoms may manifest early in infancy, or may manifest as late as adulthood. Symptoms associated with autosomal dominant porencephaly type I include migraines, hemiplegia or hemiparesis, seizures, cognitive impairment, strokes, dystonia, speech disorders, involuntary muscle spasms, visual field defects, and hydrocephalus.

Where known, the ICD-10 code is listed below.

- Anencephaly (Q00.0)

- Colpocephaly (ICD10 unknown)

- Holoprosencephaly (Q04.2)

- Ethmocephaly (ICD10 unknown)

- Hydranencephaly (Q04.3)

- Iniencephaly (Q00.2)

- Lissencephaly (Q04.3)

- Megalencephaly (Q04.5)

- Microcephaly (Q02)

- Porencephaly (Q04.6)

- Schizencephaly (Q04.6)

In babies that are born at term risk factors include problems with the placenta, birth defects, low birth weight, breathing meconium into the lungs, a delivery requiring either the use of instruments or an emergency Caesarean section, birth asphyxia, seizures just after birth, respiratory distress syndrome, low blood sugar, and infections in the baby.

After birth, other causes include toxins, severe jaundice, lead poisoning, physical brain injury, stroke, abusive head trauma, incidents involving hypoxia to the brain (such as near drowning), and encephalitis or meningitis.

Oculocerebrocutaneous syndrome (also known as Delleman–Oorthuys syndrome) is a condition characterized by orbital cysts, microphthalmia, porencephaly, agenesis of the corpus callosum, and facial skin tags.

The only certain way to prevent FAS is to avoid drinking alcohol during pregnancy. In the United States, the Surgeon General recommended in 1981, and again in 2005, that women abstain from alcohol use while pregnant or while planning a pregnancy, the latter to avoid damage even in the earliest stages (even weeks) of a pregnancy, as the woman may not be aware that she has conceived. In the United States, federal legislation has required that warning labels be placed on all alcoholic beverage containers since 1988 under the Alcoholic Beverage Labeling Act.

There is some controversy surrounding the "zero-tolerance" approach taken by many countries when it comes to alcohol consumption during pregnancy. The assertion that moderate drinking causes FAS is said to lack strong evidence and, in fact, the practice of equating a responsible level of drinking with potential harm to the fetus may have negative social, legal, and health impacts. In addition, special care should be taken when considering statistics on this disease, as prevalence and causation is often linked with FASD, which is more common and causes less harm, as opposed to FAS.

For many adopted or adults and children in foster care, records or other reliable sources may not be available for review. Reporting alcohol use during pregnancy can also be stigmatizing to birth mothers, especially if alcohol use is ongoing. In these cases, all diagnostic systems use an unknown prenatal alcohol exposure designation. A diagnosis of FAS is still possible with an unknown exposure level if other key features of FASD are present at clinical levels.