Infantile spasms have an identifiable cause in roughly 70 to 75 percent of cases. The causes fall into three broad timing categories: prenatal (before birth), perinatal (during or shortly after birth), and postnatal (later in infancy). In the remaining cases, no underlying cause can be found despite thorough testing.
This is a rare seizure disorder, affecting 1.6 to 4.5 per 10,000 live births, which translates to about 2,000 to 2,500 new cases each year in the United States. Understanding the cause matters because it shapes both treatment choices and long-term outlook.
Prenatal Causes: Problems That Begin Before Birth
The largest group of causes involves conditions that develop while the brain is still forming in the womb. These include structural brain malformations, genetic conditions, chromosome abnormalities, and infections passed from mother to baby during pregnancy.
Tuberous sclerosis complex (TSC) deserves special attention because it is the single most common identifiable cause, accounting for 10 to 30 percent of prenatal cases. TSC causes benign growths to develop in the brain and other organs. Among all children with TSC, roughly 47 percent go on to develop infantile spasms. This is why doctors specifically screen for TSC when a baby is diagnosed with spasms.
Structural brain malformations are another major prenatal cause. These include conditions where the brain’s outer surface doesn’t fold properly, where one side of the brain grows abnormally large, or where certain brain regions fail to develop altogether. MRI scans can reveal these abnormalities, which disrupt the normal electrical signaling in the brain and set the stage for spasms.
Chromosome conditions like Down syndrome (trisomy 21) also carry an elevated risk. Other prenatal causes include fluid buildup in the brain (hydrocephalus) and certain skin-and-brain conditions like Sturge-Weber syndrome.
Genetic Mutations
Beyond large-scale chromosome problems, specific gene mutations can directly cause infantile spasms. Three genes linked to X-chromosome-related infantile spasms are ARX, CDKL5, and SCN1A. Mutations in these genes interfere with how brain cells develop and communicate, though scientists are still working out the precise pathways involved.
CDKL5 mutations, for example, disable a protein that helps regulate signaling between brain cells. The result is severe seizures, including infantile spasms, that typically appear in the first months of life, predominantly in girls. ARX mutations tend to affect boys and are associated with both spasms and intellectual disability. As genetic testing has become more accessible, doctors are identifying gene-level causes in cases that would previously have been labeled “unknown.”
Birth Injuries and Oxygen Deprivation
Complications during labor and delivery are a well-established perinatal cause. The most significant is hypoxic-ischemic encephalopathy (HIE), a type of brain injury caused by reduced blood flow or oxygen to the baby’s brain around the time of birth.
Not every baby with HIE develops infantile spasms, but the risk climbs sharply with the extent of brain damage. In one study, babies who went on to develop spasms after HIE had significantly more widespread injury. Cortical damage covering more than 50 percent of the brain surface carried nearly 12 times the odds of developing spasms compared to babies with less extensive injury. Damage to the midbrain carried 13 times the odds, and injury to deep brain structures like the basal ganglia and thalamus was present in every case that progressed to spasms.
The prevailing theory is that damage to these deep structures disrupts the normal checks and balances between the brain’s outer layer (cortex) and its deeper relay centers. When that communication breaks down, the abnormal electrical patterns characteristic of infantile spasms can emerge. Intracranial hemorrhage, stroke around the time of birth, and head trauma in early infancy work through similar mechanisms.
Metabolic and Nutritional Causes
A smaller but important group of cases stems from metabolic disorders, conditions where the body can’t properly process certain nutrients or chemicals. These are worth identifying because some are treatable.
Pyridoxine-dependent epilepsy is the clearest example. Babies with this condition have seizures, including infantile spasms, that don’t respond to standard seizure medications but resolve with large doses of vitamin B6 (pyridoxine). These babies aren’t deficient in B6 in the usual sense. Instead, a mutation in the ALDH7A1 gene disrupts an enzyme needed to break down the amino acid lysine. The resulting chemical buildup interferes with signal transmission between brain cells. Two related genetic conditions (caused by mutations in the PNPO and PLPBP genes) produce similar B6-responsive seizures through slightly different pathways.
Other metabolic causes include maple syrup urine disease, phenylketonuria (PKU), and various disorders affecting how cells store or recycle waste products. Mitochondrial diseases, which impair the energy-producing machinery inside cells, can also trigger spasms. Many of these conditions are screened for at birth through newborn blood spot testing, but not all are caught early.
Postnatal Infections and Injuries
Infections that reach the brain after birth, particularly bacterial meningitis and viral encephalitis, can cause enough inflammation and damage to trigger infantile spasms weeks or months later. Head trauma sustained after birth, whether accidental or inflicted, is another recognized postnatal cause.
When No Cause Is Found
In roughly 8 to 42 percent of cases, depending on how extensively doctors investigate, no underlying cause can be identified. These cases fall into two groups. “Cryptogenic” means the doctor suspects an underlying cause exists but can’t pinpoint it with available testing. “Idiopathic” is reserved for the small subset of babies who were developing normally before spasms began, have a normal neurologic exam, and show no abnormalities on brain imaging.
The wide range in that percentage reflects real differences in how thoroughly each baby is evaluated. A child who receives advanced genetic testing and high-resolution MRI is more likely to get a specific diagnosis than one who doesn’t. As genetic testing continues to improve, fewer cases remain unexplained.
How the Cause Affects Treatment
First-line treatment for infantile spasms typically involves hormone therapy (either a steroid or ACTH, a hormone that stimulates the adrenal glands), sometimes combined with an anti-seizure medication called vigabatrin. The treatment course is relatively short, usually about two weeks of active therapy followed by a gradual taper.
The major exception is tuberous sclerosis complex. Babies with TSC-related spasms respond better to vigabatrin alone, so it is used as the preferred first treatment in those cases. For pyridoxine-dependent epilepsy, high-dose vitamin B6 is the specific treatment, making early identification of this cause especially valuable.
Identifying the cause also shapes expectations about development. Babies with idiopathic spasms, where no underlying brain problem is found, generally have the best developmental outcomes. Those with extensive structural brain damage or severe genetic conditions face greater challenges, though early and aggressive treatment of the spasms themselves can still improve the trajectory. Speed matters: the longer spasms continue before treatment begins, the greater the potential impact on a child’s developing brain.