Evaluation of the Child with Microcephaly

Q&A with Authors Stephen Ashwal, MD, FAAN, and David Michelson, MD

September 14, 2009

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Microcephaly is an important neurologic sign, but there is no uniformity in its definition and evaluation. Microcephaly may result from any insult that disturbs early brain growth and can be seen in association with hundreds of genetic syndromes. Annually, approximately 25,000 infants in the US will be diagnosed with microcephaly.

A new AAN guideline, "Practice Parameter: Evaluation of the Child with Microcephaly (an evidence-based review)," co-developed in full collaboration with the Child Neurology Society, was published in the September 15 issue of Neurology® (2009; 73:11). AAN.com asked the lead authors, Stephen Ashwal and David Michelson, to discuss how the guideline was developed. They spoke with AAN.com Science Editor Jose G. Merino, MD, MPhil.

AAN.com: How was this practice parameter developed?

Authors: The practice parameter was prepared over a two-year period using the process developed by the AAN Quality Standards Subcommittee. As such it was reviewed by about 80 individuals and went through five revisions. We followed the strict and standardized format using evidence-based medicine methods in which the strength of the recommendations was based on the strength of the evidence.

AAN.com: Can you briefly summarize the criteria for the diagnosis of microcephaly?

Authors: Microcephaly is usually defined as a head circumference (HC) of more than two standard deviations (SDs) below the mean for age and gender, although some academics have advocated for defining "severe" microcephaly as an HC more than three SDs below the mean. Microcephaly, particularly when severe or postnatally acquired, is frequently found in children with developmental delays, cognitive impairments, cerebral palsy, and epilepsy.

AAN.com: How often should neurologists and pediatricians measure head circumference, and until what age?

Authors: The head circumference should be measured at birth and then serially, along with other growth parameters, until three to five years of age. As we categorize microcephaly into two major groups (congenital and postnatal), you can see that there is a need for ongoing HC measurements. Most children who develop microcephaly present within the first two to three years of life. Accurate HC measurements can be obtained with a flexible but non-stretchable measuring tape pulled tightly across the most prominent part of the back (occiput) and front (supraorbital ridges) of the head. Standardized growth charts in percentiles for boys and girls from birth to age 36 months are available online from the website of the National Center for Health Statistics. The appendix in the parameter contains links to a website that provides head circumference charts.

AAN.com: How should clinicians approach the evaluation of children with a small head circumference?

Authors: If a child is found to have a head circumference that is below normal for age, the physician should first verify the accuracy of the measurement and then verify that the measurement was plotted appropriately for age and gender. If the child's head size is more than two SD below normal at any time in childhood, an evaluation should be considered, but what one does depends on several clinical factors that are discussed in the parameter.

AAN.com: When should neurologists and pediatricians obtain neuroimaging studies and genetic tests?

Authors: Diagnostic testing is important to try to ascertain the etiology, as it can help with prognosis about future associated risks of coexistent conditions and also help the family understand what their risks are for having additional children who might be similarly affected. Ultimately, one must use one's clinical judgment in deciding what testing should be done. When there is evidence by history or examination of a specific cause for microcephaly, further testing may be done for confirmation. When microcephaly remains unexplained, however, current data support the consideration of diagnostic tests such as neuroimaging studies and targeted genetic testing. It is likely that those having a family history of benign microcephaly or microcephaly that is proportionate with height and weight are less likely to have developmental consequences, but at this point we recommend monitoring for developmental and neurological abnormalities. We have included two algorithms in the parameter that outline a stepwise approach to how a work-up can be done.

AAN.com: What are the most frequent environmental causes of microcephaly?

Authors: The clearest prenatal causes are maternal use of alcohol, maternal use of certain medications, and poorly controlled maternal phenylketonuria. It is also possible that maternal tobacco smoking, substance abuse, and poorly controlled diabetes might contribute to the development of congenital microcephaly. In older children, lead poisoning and chronic renal failure are known to cause microcephaly (though the former is currently very rare), but it is likely that almost any type of chronic disease can contribute to the development of microcephaly.

AAN.com: What are the most common genetic syndromes associated with small head circumference?

Authors: The most common syndromic cause of microcephaly is Down syndrome, in which microcephaly is seen in 30 percent, though the diagnosis is usually readily made based on other clinical features. Other common genetic syndromes associated with microcephaly include Rett syndrome (commonly due to mutations in the MeCP2 gene) and Angelman syndrome (due to loss of function of the maternal UBE3A gene in the 15q11-13 region); these are sometimes less recognizable. A finding of microcephaly can contribute to the suspicion for these disorders. Dozens of other relatively rare genetic causes of both syndromic and non-syndromic microcephaly have been described, and there are tables and appendices in the parameter that review this information. (Read a general overview of this condition.)

AAN.com: Is there a role for genetic counseling for parents of children with microcephaly?

Authors: There is a definite role for genetic counseling for families who have a child with microcephaly. As the fields of neuroimaging and genetic testing continue to advance over the next decade, it is clear that we will be able to provide increasingly detailed information regarding the causes and recurrence risks for microcephaly. Parents appreciate physicians' efforts to "find out what is wrong with their child."

AAN.com: What studies are required to refine these guidelines and strengthen the level of evidence for the next revision?

Authors: There is a need for studies to better define the prevalence of congenital and postnatal microcephaly and to establish whether the significance of microcephaly is altered by ethnic background, a history of prematurity, head shape, and parental head size. There is also a need for neuropsychological, neuroimaging, genetic, metabolic, neurophysiologic (i.e., EEG), and ancillary (vision and hearing) testing to establish the diagnostic yields such testing and inform the development of a better evidence-based algorithmic approach to evaluation.

Author Disclosures

Dr. Ashwal serves on the scientific advisory boards of the Tuberous Sclerosis Association and the International Pediatric Stroke Society; he is also an editor of Pediatric Neurology. In addition, he receives research support from the NIH.

Dr. Michelson has nothing to disclose.

Dr. Merino performed a one-time consultation with staff from Bell, Falla and Associates. He is the AAN.com Associate Website Editor for Science.