Microcephaly: Manifestations, Causes, Treatment, and Prevention


Congenital conditions are escalating with time. One of these conditions is microcephaly. This disorder refers to a clinical condition characterized by having a smaller brain than it means for age, gender, and ethnicity (19). In this case, the occipitofrontal circumference of the head is either less than or equal to the standard deviation of -2. On the other hand, microcephaly is not a disease but a clinical condition (5). It is an occipital frontal head circumference smaller than the one expected from both gender and age. These two versions of defining the term give a revelation that in microcephaly, the size of the head is smaller than the normal one for a given gender, age, and ethnicity.

The brain is the most important thing in determining the size of the head. This fact means that everything that results in small brain mass contributes to the occurrence of microcephaly. Brain growth solely determines the size of the head since the cranium depends on forces of an expanding brain, which may imply the presence of microcephaly (5). Furthermore, the definitions of this condition have outlined lower limit of the brain size regarding head circumference, but variations may come about as a result of ethnicity (5).

The condition’s prevalence has been escalating from one region to another. According to de Araújo and the colleagues, northeast Brazil has recorded a dramatic rise in the reported number of microcephaly cases since November, 2015 (5). An example can be provided from Brazil, where the rates of the condition have been increasing due to various factors, especially the increased prevalence of the zika viral infections. In 2000, the Brazilian Live Birth Information System (SINASC) reported that there were 5.5 cases of microcephaly in every 100,000 live births (5). However, the number rose to 5.7 cases in 2010. After a while, the number increased to 99.7 cases in every 100,000 live births. This increase is alarming and is often associated with the occurrence of the zika viral infection among the Brazilians. In their study, de Araújo and the colleagues found that the total number of microcephaly cases reached 3,000 in 20 Brazilian states during the period between 2012 and 2015 (5). However, the US has reported little figures of the condition; it should work hard to minimize further the challenge. The researchers in the US estimate that microcephaly cases range from 2 to 12 babies per 10,000 live births (13).

Numerous factors are behind the cause of microcephaly. Genetics, infections, malnutrition, and exposure to harmful substances such as drugs can result in this congenital condition (7). The signs and symptoms of microcephaly are characterized by brain function alterations. However, there is no treatment to heal the problem once it has occurred. The only treatment aims at preventing the condition from occurring at all (7). This topic is important because it addresses the issues affecting human life from birth. Moreover, knowing the condition and the way of avoiding it is a key towards the realization of a healthy society, which can only be realized through precisely addressing the topic among others. This paper looks forward to discussing and explaining the causes, manifestations, treatment, and prevention of microcephaly.

Microcephaly Causes

Both genetic and environmental factors cause this condition. Among the genetic causes, centrosome amplification determines brain growth and development (11). In their research, Marthiens et al. found that the brain is one of the tissues vulnerable to centrosome mutations. Some of these mutations result in centrosome amplification, which hinders the normal growth of the brain, hence causing microcephaly. In proving the validity of this argument, autosomal recessive primary microcephaly (MCPH) in humans is a neuro-developmental disorder, which is often accompanied by a proportionate reduction in the size of the brain at birth. Several centrosome mutations causing multiple centrosome abnormalities (e.g. increased number of centrosomes) have been present in MCPH families (11).

There must be some particular ways through which centrosome amplification slows the brain growth and development which consequently results in microcephaly. Within the centrosomes, spindles are affected leading to marked defects whenever mutations occur. Spindle positions are important in genetics since position defects have been attributed to be the cause of MCPH (11). The reason for the implication is that the defective spindle positions cause premature neurogenesis, which, in its turn, depletes neural stem cells. Moreover, the defects in cell division as well as cell death can result in mutations. Such problem causes the depletion of the neural stem cell pool leading to low and insufficient brain growth, and this development makes newborns possess small brain sizes compared to the normal ones (11).

In detail, several loci for MCPH have been identified, and most of them show an effect on either spindle or centrosome associated genes (11). During neural stem cell division, spindle position defects result in smaller brain volumes than the average due to premature depletion of progenitor pool. Furthermore, the defects cause increased cell death through the process of apoptosis. Therefore, centrosome amplification together with cell death and aneuploidy are behind the occurrence of microcephaly.

On the other hand, retinoblastoma binding protein 8 (RBBP8) mutations can cause microcephaly. Mumtaz et al. assert that RBBP8 mutations are the causative factors for the four types of autosomal recessive microcephaly syndromes (12). This mutation results in Jawad syndrome, which clinical features are learning disability, syndactyly, polydactyly, anonychia, and microcephaly (12). Also, there are cases in which such individuals are born with short stature and even dwarfism. This phenomenon is indicative of the reduced growth of not only the brain but also other body parts secondary to the mutations affecting RBBP8. The mutation reveals that microcephaly is only one of the consequences among many others.

Moreover, DNA damages and repair activities can lead to the occurrence of microcephaly. There are marked relationships between microcephaly genes and the DNA damage responses as well as its repair pathways along with genomic integrity pathways maintenance (8). Similarly, different mechanisms of repair exist for different types of DNA damages. For instance, a damage of the double-stranded DNA resulting in its breakage leads to the activation of the repair pathway. As a result, arresting of the cell cycle occurs to allow the completion of the repair process. If the damage is very severe, activation becomes evident. Finally, particular enzymatic proteins in the repair pathways set to coordinating the repair after which normal cell cycle proceeds. Due to the delay in the process of repair, brain development is delayed, thus resulting in microcephaly.

Apart from the genetic causes of microcephaly, there are several environmental factors behind this health threatening condition. Hypoxic-ischemic encephalopathy (HIE) is the chief cause of acquired microcephaly (14). Although HIE occurs in about 1.5-6 cases in every 1,000 live births, over 48% of the cases are accompanied by microcephaly (17). The neurological injuries are caused by low levels of oxygen in various parts of the brain. Such injuries may occur before, during, and after birth, which means that microcephaly can occur even among babies born with normal heads and brain sizes (10). The damage to the growing brain hampers the normal growth and development, thus causing microcephaly. Children with such injuries may have multiple manifestations in terms of the affected body parts.

Notwithstanding this, there are more causes of microcephaly occuring mostly during pregnancy. Among them, one can find the exposure to toxic processes or chemicals such as radiological emissions and prescribed drugs, which may affect the fetus (7). Also, gestational infections can result in poor brain development of the unborn child. Such infections originate from pathogenic organisms such as rubella, varicella, and cytomegalovirus among many others. Women who smoke and drink alcohol during pregnancy predispose their unborn children to many health conditions, and microcephaly is not an exception here.

Of late, Zika virus (ZIKV) has a relationship with microcephaly because, with the increase in the viral infection, this condition also increases. This phenomenon gives a hint that ZIKV causes microcephaly. The detailed evidence supporting this fact can be drawn from the researches done in Brazil regarding the condition and its connection with the virus. Brazil is the region where ZIKV infection prevalence is one of the highest in the world. ZIKV is a flavivirus with its vector being the Aedes mosquito (6). In early 2015, this viral outbreak occurred in northeast Brazil. By September of the same year, the number of infants with microcephaly began to rise in areas affected with the virus. Furthermore, the Brazilian health workers identified two prenatal cases with microcephaly by ultrasound scan. When this was done, the amniotic fluid analysis revealed the presence of ZIKV.

In January 2016, the total number of cases regarding this health condition was 3,530, the majority of which came from the population that either visited or lived in the areas where ZIKV was prevalent (6). In February 2016, the World Health Organization suspected the connection between the virus and microcephaly and called it as “Public Health Emergency of International Concern” (4). Such findings are a clear indication that there is a strong correlation between Zika virus and microcephaly.

Along the same line, the Brazilian Ministry of Health released a report in November, 2015. It declared an increase in the number of microcephaly cases, especially in the state of Pernambuco (16). Despite realizing an increase in the prevalence of the condition, the government did not suggest the definitive cause. However, it took a firm stand to associate the rise with the ZIKV infection. This bold move raised concerns as to whether ZIKV infections caused the condition, had no effect on the coincidence, or correlated with it. At that moment, there were no certain answers. However, with a close follow-up on the viral studies and the mechanisms resulting in microcephaly, it is possible to prove the correlation.

Zika viral RNA has been present both in the amniotic fluid samples and the mothers’ blood (16). This finding reveals that once the mother gets infected with ZIKV, then the fetus can be affected in the same way since viral transfer happens across the placenta. According to Tetro, ZIKV has the potential to not only infect fetuses, but also cause conditions like microcephaly through neurodevelopmental dysfunctions (16). In spite of using mice as study subjects, scientists have revealed that the virus has demonstrated tropism in the brain of a fetus. Such a thing means that ZIKV has the potential to cross the selective blood-brain barrier. One of the researches was done by infecting mice with the virus, which resulted in direct infection of the brain (16). Based on mere observations and other investigations, this virus infected glia and neurons, which, in turn, produced several intracytoplasmic inclusions called the “viral factories” (16). Endoplasmic reticulum was the source of these factories that had a connection with both mitochondria and nucleus. In addition to the link established between ZIKV and the increase in microcephaly cases in Brazil, the effect of the infection on the brain shows a clear correlation between the virus and the health condition.

Manifestations of Microcephaly

The first obvious sign of this condition is the small size of the affected individual’s head. Infants born with microcephaly have a smaller head than the average-sized one for a given age, gender, and ethnicity (5). The determination of head size is realized by measuring the occipital frontal circumference (5). The head circumference that is less than or equal to -2 of the standard deviation is indicative of microcephaly. Moreover, if the circumference is -3 or less, then the infant has severe microcephaly. Another unique and typical feature of the condition in severe cases is the backward sloping forehead (15).

Brain involvement is the key in manifestations since the brain is the primary organ with abnormalities in this condition. Therefore, the signs and symptoms relate directly to the brain malfunctions. However, some children may lack these signs and symptoms except for the small head size. The scholars from Boston Children’s Hospital say that some of the children with this condition display normal intelligence without any difficulties in physical activities, schoolwork, and relationships among many other aspects of life (3). In this case, such children do not have brain damage except for the brain mass being only reduced. In this case, however, the functional capacity is intact.

Signs and symptoms are manifest and visible if the condition is severe. Depending on its severity, the brain malfunctions occur, which is revealed through the performance of normal daily activities. Children may have impaired cognitive development resulting in intellectual disabilities. Such children may have difficulties in meeting schoolwork requirements, thus having poor performance (7). Therefore, delayed motor functions and speech make the affected children unable to perform physical activities, establish and maintain relationships. Facial distortions and dwarfism are also common among the affected children (7). Such things influence self-esteem, which may make a child withdraw from socialization, which often results into depression. Concerning the part of the brain impacted by the condition, the affected children may have hyperactivity, difficulties in balance, coordination, and seizures (7). Furthermore, some children manifest hearing and vision problems that may include deafblindness among many other neurological abnormalities.

Treatment of Microcephaly

Once a child is born with microcephaly, there is no substantial treatment for returning the size of the head to normal (15).The only treatment offered aims at decreasing the impact of the condition associated malformations as well as neurological disabilities. Before treating the condition, proper diagnosis in which pediatric neurologists evaluate the child is essential. Afterwards, various medical professionals come in with an aim of treating the symptoms. If the cause of the condition is related to genetic factors, then genetic counseling plays a key role (13). Parents of infants born with this health problem receive detailed information about its origin.

Children with physical challenges need physiotherapy to improve their physical capabilities (13). The therapy may involve teaching the children on how to do simple things that may be important for human survival. Along the same line, the symptoms of impaired speech may need a speech therapist to intervene in the challenge (13). All these treatments together with occupational therapy help not only in minimizing dysfunction but also in maximizing abilities. Smith explains that other than surgery, no treatment can cure microcephaly. The symptomatic treatment involves physical, speech, and, pharmacological occupational therapies among others (15). Craniosynostosis, which is known for causing microcephaly, involves premature fusion of skull bones, something that impairs the proper growth of the brain (15). Craniosynostosis is the only cause of microcephaly, which is reversible upon surgical interventions to help in reshaping the skull.

Other complications that require serious treatment are hyperactivity and seizures. The common drugs used in the treatment of hyperactivity are amphetamine, methylphenidate, and the infamous non-stimulant drug called atomoxetine (9). Sometimes, clonidine and carbamazepine may be used despite the lack of approval from the Food and Drugs Authority [FDA] (9). The treatment of seizures has been administering for a long time. The most common drugs for treating epilepsy, which is a complication of microcephaly, are carbamazepine and sodium valproate (2). Although phenobarbitone and phenytoin were used as drugs of choice, they are currently not the first, second, and third line medications for seizures in children (2). However, they may be effective in some situations, especially when other drugs have failed.

Prevention of Microcephaly

Since the causes of microcephaly are known, some of them can be prevented through various endeavors. Concerning ZIKV, there is no known vaccine against the virus (18). However, there are several measures in avoiding its infections. Pregnant women should avoid traveling to areas with the outbreaks of this lethal virus (18). Such a thing prevents the unborn children from getting the infection that, as it was stated above, increases the risk for microcephaly. In addition to this, the individuals in areas with mosquitoes should avoid being bitten by them. The reason for this is that Aedes mosquito is the main vector of the virus, and its bites can transmit the disease to a human. Ahmad, Amin, and Ustianowski explain that people in endemic areas should protect their bodies by wearing long sleeves and trousers among many other safety measures in order to minimize skin exposure so as to defend themselves from mosquito bites (1).

Furthermore, people should sleep in rooms with insecticide-treated mosquito nets (1). Houses should also have screens, especially on the windows and doors to prevent mosquitoes’ entry into the houses. Also, pregnant mothers are supposed to apply insect repellents approved by the appropriate local health authorities (18). Since ZIKV transmissions may happen through sexual intercourse, sexual partners of pregnant women who either live in or are returning from areas prone to the viral transmission should employ safer practices such as abstinence from having sex for a given time (18). Such a thing is important in safeguarding the fetus against any potential viral infection that is likely to cause microcephaly.

More so, HIE prevention is important in resisting microcephaly (14). In doing that, the avoidance of injuries for pregnant women is the key before, during, and after delivery. The injuries are part of the things that result in brain’s deficiency in oxygen, hence causing HIE. Furthermore, neurological injuries impairs fetus’s mental functional capacity in addition to resulting in small head size (10). Pregnant women should also avoid exposure to radiological emissions, which often affect brain of a fetus among its other body parts. Women should also seek for prenatal health care that not only helps in preventing infectious diseases but also enhance early detection and treatment of any infection. Such a move aids in protecting fetuses against infections likely to affect their nervous system. Also, the avoidance of smoking and alcohol as well as of taking in non-prescribed medication can help in reducing the risk of microcephaly.


Microcephaly is not a disease but a condition in which an individual’s head size is smaller than the normal one of corresponding age, gender, and ethnicity. The growth and development rate of the brain determine the size of the head. When the brain grows slowly, the head’s occipital frontal circumference becomes smaller than usually resulting in the condition. Of late, microcephaly has been on the rise, especially in Brazil. Causes of this problem vary from environmental to genetic factors. Among the genetic factors, one may distinguish mutations that entail centrosome amplification, RBBP8, DNA damages, and repair pathways. In centrosome amplification and RBBP8 mutations, there are abnormal chromosomal activities that result in delayed brain development and its abnormal growth. Such a thing causes severe conditions, among which affecting the brain (i.e. microcephaly) is not an exception. Moreover, DNA damages induce appropriate repair pathways. Once the repair pathways are activated, the cell cycle gets arrested, and apoptosis happens. As a result of this genetic processes, brain growth and development is delayed, thus causing microcephaly. Furthermore, there are other causes of this condition that include HIE and viral infections from varicella, rubella, and cytomegalovirus among many others. Pregnant mothers who smoke, take alcohol, and get poor nutrition predispose their unborn children to this health threatening condition.

There is a straight connection between ZIKV and microcephaly. Brazil is one of the countries that has established clear correlation between the two. In this nation, the increase in the transmission of the virus resulted in a marked increase in the number of cases of microcephaly. Besides, healthcare professionals identified the virus in the amniotic fluid and the mothers’ blood after detection of fetal microcephaly through ultrasonography. Such a finding revealed that these two issues are interconnected.

Microcephaly is manifested in many ways. One of the most obvious sign of the condition is the small head as for age, gender, and ethnicity. Some of the cases are asymptomatic, and the children with the condition do not have any mental problems except for their small head size. However, some of these children demonstrate poor cognitive functions, dwarfism, intelligence instability, delayed motor dysfunctions, seizures, hyperactivity, hearing and visual problems among many others. Other than surgical interventions in cases of craniosynostosis, there is no treatment for the condition. Therefore, treatment of the affected children aims at maximizing their abilities and minimizing their disabilities through symptomatic management. Physical, occupational, pharmacological, and speech therapies have proven to be effective in the treatment of symptoms. Prevention of this condition aims at resisting some of the causes and risk factors. For instance, prevention of infections from viruses like ZIKV and rubella virus plays a substantial role.

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