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Microcephaly: A clinical genetics approach

Geoff Woods, ChB, MB, MD, FRCP, FMedSci
Section Editor
Helen V Firth, DM, FRCP, DCH
Deputy Editor
Mary M Torchia, MD


Microcephaly is an important neurologic sign. Deviations from normal head growth may be the first indication of an underlying congenital, genetic, or acquired problem. Many genetic conditions are associated with an abnormal pattern of head growth; the earlier these conditions are detected, the earlier appropriate treatment, services, and genetic counseling can be provided [1].

A clinical genetics approach to microcephaly in infants and children will be presented here. At the heart of this approach is an attempt in each case to formulate an etiological diagnosis that gives at least an indication of the sibling recurrence risk. The etiology and primary care evaluation of microcephaly in infants and children and microcephaly related to Zika virus are discussed separately. (See "Microcephaly in infants and children: Etiology and evaluation" and "Zika virus infection: An overview", section on 'Children'.)


The definition of microcephaly is not standardized. It is sometimes defined as an occipitofrontal circumference (OFC) more than 3 standard deviations (SD) below the mean for a given age, sex, and gestation. Other times, it is defined as an OFC more than 2 SD below the appropriate mean (ie, less than the 3rd percentile).

OFC measurements at birth are necessary to establish a diagnosis of primary microcephaly (see 'Primary microcephaly and its syndromes' below). It can be difficult to measure OFC accurately in children with severe microcephaly without the landmark of the occiput. It is important to record measurements rather than percentiles – as head circumference charts vary, especially up to the age of three years, and to use the most recent culturally and ethnically relevant charts to determine percentiles [2].

If microcephaly is defined as a head size less than 3 SD below the appropriate mean, it is more likely to be associated with genetic and non-genetic disorders affecting brain development. In contrast, if microcephaly is defined as more than 2 SD below the mean, many intellectually normal individuals who have a head circumference at the low end of the population distribution will be included.


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Literature review current through: Sep 2016. | This topic last updated: Apr 20, 2016.
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