Microcephaly is a medical condition where a baby’s head is significantly smaller than expected compared to babies of the same age and sex. This small head size usually reflects an underdeveloped brain, which can lead to developmental delays, intellectual disabilities, and other neurological problems. Understanding what causes microcephaly involves exploring a wide range of genetic, environmental, and infectious factors that interfere with normal brain growth during pregnancy or shortly after birth.
At its core, microcephaly results from disruptions in brain development. The brain grows rapidly during fetal life, especially in the first and second trimesters of pregnancy. If something interferes with this growth, the brain may not develop fully, leading to a smaller skull and head size. The causes can be broadly grouped into genetic mutations, infections, exposure to harmful substances, and other prenatal complications.
**Genetic Causes**
Many cases of microcephaly are linked to genetic mutations. These mutations can affect genes that are crucial for brain development and cell growth. For example, mutations in genes like *DHX37* have been identified in children with primary microcephaly, where the condition is present at birth and not caused by other brain injuries. These gene variants can disrupt the normal processes of cell division, growth, and repair in brain tissue, leading to reduced brain size.
Some genetic syndromes that include microcephaly as a feature are caused by deletions or mutations in specific chromosomes or genes. For instance, chromosome 15q13.3 microdeletion syndrome involves the loss of several genes on chromosome 15, which can result in microcephaly among other symptoms. Other inherited conditions, such as Meckel syndrome, caused by mutations in multiple genes, also include microcephaly as part of their clinical presentation.
In addition to single-gene mutations, some gene variants can indirectly contribute to microcephaly by affecting metabolic pathways. For example, mutations in the MTHFR gene can lead to elevated homocysteine levels, which may cause vascular damage and developmental delays, potentially impacting brain growth.
**Infectious Causes**
Infections during pregnancy are a well-known cause of microcephaly. Certain viruses can cross the placenta and infect the developing fetus, damaging brain cells or interfering with brain development. The most infamous example is the Zika virus, which caused a significant increase in microcephaly cases during outbreaks in recent years. Other infections linked to microcephaly include cytomegalovirus (CMV), rubella, toxoplasmosis, and herpes simplex virus.
These infections can cause inflammation, cell death, or disrupt the formation of brain structures, leading to a smaller brain and head size. The timing of infection during pregnancy is critical; infections in the first trimester tend to have the most severe effects because this is when the brain is forming its basic structures.
**Environmental and Maternal Factors**
Exposure to harmful substances during pregnancy can also cause microcephaly. This includes alcohol, certain drugs, toxic chemicals, and radiation. For example, fetal alcohol syndrome, caused by heavy alcohol consumption during pregnancy, often results in microcephaly along with other facial and developmental abnormalities.
Severe malnutrition or lack of essential nutrients during pregnancy can impair fetal brain growth. Deficiencies in folic acid, for example, are known to cause neural tube defects and may contribute to microcephaly. Maternal health conditions such as uncontrolled diabetes or severe infections can also increase the risk.
**Other Prenatal and Perinatal Causes**
Sometimes, microcephaly results from complications during pregnancy or birth that reduce oxygen supply to the baby’s brain (hypoxia) or cause brain injury. For example, severe prematurity, placental insufficiency, or trauma during delivery can damage the brain and lead to microcephaly.
In some cases, microcephaly is part of a broader syndrome involving multiple organ systems, where brain growth is just one affected aspect. These syndromes
