Small head circumference - microcephalus

Types

There are several causes of small head circumference:

Benign familial microcephalus: the head circumference is small with no additional problems and without mental retardation. It is known that the head circumference is determined genetically, and there are many families whose members have a small head circumference with completely normal intelligence and no other problems.
Microcephalus can occur together with other complex defects, such as other defects in the brain and/or in other organs.
It can be part of a wide variety of syndromes.
Microcephalus can be due to environmental damage to the developing brain tissue, for example, significantly reduced blood flow to the entire fetus or to the brain tissue in particular (see cerebral palsy), intrauterine infection, etc.

Clinical signs

The benign familial type of microcephalus

In the fetus the head circumference is smaller than average for the week of gestation. A slightly smaller than average head circumference is a relatively common finding and is of no medical significance if it is within the normal range and if one of the parents also has a smaller than average head circumference as measured with a regular tape measure.

True microcephalus (below the normal range) is defined as a head circumference two standard deviations below the average for the age or week of gestation. The frequency is approximately 3% of the normal population. It is not usually associated with any specific medical problems, especially if the microcephalus is also present in one of the parents and this parent is healthy and normal. It is known that the head circumference is established genetically and there are many families with members with microcephalus without any other problems. However, it must be ascertained that the patient being examined is not one of the exceptions listed below.

Microcephalus with genetic problems

When should non-benign microcephalus be suspected?

When the microcephalus in the parents or other relatives is in the range considered "normal" and therefore this does not explain the fetus's (or neonate's/child's) microcephalus.
If the fetus's head circumference was normal, and then stops growing within a carefully monitored timeframe.
There is an increase in the volume of fluid in and around the ventricles of the brain, which is a manifestation of decreased brain volume within the vault of the skull, which is too small.
Markedly severe microcephalus - usually at more than 3 standard deviations below the mean there is a marked increase in mental retardation, and at more than 3.5 standard deviations below the mean, the risk for mental retardation jumps to 70% - 80%, even if the cause is not genetic but environmental, e.g. decreased blood flow to the fetus in the uterus.
There are other defects in the brain, for example absent corpus callosum, which is the structure that connects the two cerebral hemispheres, or defects in other organs with or without brain defects, or functional deficits such as reduced movements in the uterus, etc. and polyhydramnios.
There is a family history of other cases of microcephalus with mental retardation, etc.

Genetic diseases and syndromes associated with microcephalus are many and diverse, noteworthy of which are the following:

Chromosomal syndromes. These include Down syndrome and also other chromosomal problems such as a deletion of chromosomal material in the short arm of chromosome 5 or a deletion/insertion in another chromosome.
An autosomal recessive condition featuring microcephalus with mental retardation - the risk for this is increased if the parents are related. In this genetic disease there are no external defects apart from microcephalus and there is no environmental cause that can account for it. The head structure is characteristic with a backward-sloping forehead, and this assists in the diagnosis.
Genetic diseases leading to abnormal intrauterine development of the brain tissue and/or metabolism of the developing brain - these cases are usually marked by abnormal brain structure that can usually be detected only towards the end of pregnancy or after birth. Recently, fetal magnetic resonance imaging (MRI) has been introduced, and this enables identification of some of these cases in the third trimester of pregnancy.
Uncommonly, but in some cases of extreme microcephalus, this can be part of the spectrum of anencephalus and neural tube defect.
There are hundreds of different genetic syndromes associated with microcephalus, including defects or other deficiencies. These include albinism, immune system disorders, congenital bone diseases, etc.
Other rare diseases involving regression of the size and volume of the brain that usually only occurs after birth. Examples are Rett syndrome, which affects girls almost exclusively, and Angelman syndrome, etc. In these cases, as noted, there are no signs of microcephalus during the pregnancy.

Microcephalus following environmental damage

Most cases in this group result from a marked decrease in the blood flow to the fetus in general or to the brain in particular (see cerebral palsy).

When the decreased perfusion occurs in the uterus, there is a reduction in the growth of all fetal parameters including the circumference of the abdomen, length of femur, etc., and a decrease or cessation of the growth of the head is possible.

In these cases, there is usually oligohydramnios (reduced amniotic fluid) and a risk of premature birth and/or sudden intrauterine death, depending on the type and severity of the disorder. When the decreased perfusion occurs in the perinatal period, or up to a few months after birth, the microcephalus is gradual, taking months to develop.

Intrauterine infection (CMV and Toxoplasma) can also lead to a gradual decrease in the growth rate of the brain and also mental retardation (see separate information sheets).

Implications for neurological problems in microcephalus

Atypical cases in which there is marked microcephalus, which is relatively rare, are associated with developmental delay and/or genetic syndromes and/or other problems such as epilepsy. The risk for these increases if there are such problems as:

The fetal head circumference was normal and then stops growing within a short time interval during careful monitoring.
There is an increase in the volume of fluid in and around the ventricles of the brain, which is a manifestation of decreased brain volume within the vault of the skull, which is too small.
Markedly severe microcephalus - usually at more than 3 standard deviations below the mean there is a marked increase in mental retardation, and at more than 3.5 standard deviations below the mean, the risk for mental retardation jumps to 70% - 80%, even if the cause is not genetic but environmental, e.g. decreased blood flow to the fetus in the uterus.
There are other defects in the brain, for example absent corpus callosum, which is the structure that connects the two cerebral hemispheres, or defects in other organs with or without brain defects, or functional deficits such as reduced movements in the uterus, etc. and polyhydramnios.
There is a family history of other cases of microcephalus with mental retardation, etc.

Inheritance pattern

The benign familial form of microcephalus is transmitted by autosomal dominant inheritance.
Microcephalus as part of a genetic syndrome - this depends on which syndrome the patient has. The type of microcephalus that is accompanied by mental retardation with no other associated defects is transmitted by autosomal recessive inheritance.
Microcephalus following environmental damage is, of course, not genetic.

Penetrance

The penetrance of microcephalus in genetic syndromes is more or less complete, but there may be differences in severity between affected people, even in the same family. It should be noted that in some types of microcephalus, the head circumference is normal, and the microcephalus can be diagnosed only in the last stages of pregnancy and sometimes even after birth or at a few months of age.

Associated features that can be demonstrated in tests performed during pregnancy

It is important to monitor the head circumference since the head usually grows at a constant rate. There are growth curves, and the growth of the head is usually in accordance with the average, but there does not necessarily have to be an average. Therefore the change in the rate of the growth of the head manifests as a decrease or increase of the head growth gradient in comparison with the average. Such a change is very important for assessing the situation. Of course, measuring the parents' head circumferences, along with those of other relatives, including siblings, uncles and aunts, is essential.

In ultrasound testing, other defects in the brain, such as absence of the corpus callosum, etc., should be noted, and also whether there is an increase in the amount of fluid in or around the ventricles. Attention must be paid to limb movements, the amount of amniotic fluid (polyhydramnios may indicate a problem in the swallowing of amniotic fluid), and other defects.

In recent years, a new technique for scanning the fetal brain using high-speed magnetic resonance imaging (MRI) devices has been developed. This was not possible before because the fetus often moves, and the older MRI machines were not quick enough. Cumulative experience shows that this test has a great advantage in identifying defects that cannot be detected by ultrasound, and it is recommended in cases of hydrocephalus or microcephalus.

Chromosome analysis of blood or amniotic fluid is advisable, and essential in cases where the microcephalus is of unknown cause.

If there are family members with genetic syndromes or mental retardation, they should be examined by a geneticist.

The mother's blood can be examined to test for infection by some of the common pathogens. If the cause is found to be a viral infection that is known to cause microcephalus, there is, of course, an increased risk of fetal growth retardation.

In all these cases it is important to refer the couple for genetic counseling, to which they should bring all data, including the results of other tests performed during the pregnancy such as alpha-fetoprotein, nuchal translucency, etc.

In cases of significant microcephalus it is advisable to refer the parents to a multidisciplinary clinic in a hospital for professional counseling by a pediatric neurologist, a geneticist, an expert in ultrasound examinations and a neonatologist, in order to collate all the data and discuss the various possibilities and courses of treatment that are available, etc. The decisions taken will depend on the severity of the problem, the presence of additional findings, etc.