Objective: To make evidence-based recommendations concerning the evaluation of the child with microcephaly. Methods:Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a 4-tiered scheme of evidence classification. Results:Microcephaly is an important neurologic sign but there is nonuniformity 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 United States will be diagnosed with microcephaly (head circumference ϽϪ2 SD). Few data are available to inform evidence-based recommendations regarding diagnostic testing. The yield of neuroimaging ranges from 43% to 80%. Genetic etiologies have been reported in 15.5% to 53.3%. The prevalence of metabolic disorders is unknown but is estimated to be 1%. Children with severe microcephaly (head circumference ϽϪ3 SD) are more likely (ϳ80%) to have imaging abnormalities and more severe developmental impairments than those with milder microcephaly (Ϫ2 to Ϫ3 SD; ϳ40%). Coexistent conditions include epilepsy (ϳ40%), cerebral palsy (ϳ20%), mental retardation (ϳ50%), and ophthalmologic disorders (ϳ20% to ϳ50%).Recommendations: Neuroimaging may be considered useful in identifying structural causes in the evaluation of the child with microcephaly (Level C). Targeted and specific genetic testing may be considered in the evaluation of the child with microcephaly who has clinical or imaging abnormalities that suggest a specific diagnosis or who shows no evidence of an acquired or environmental etiology (Level C). Screening for coexistent conditions such as cerebral palsy, epilepsy, and sensory deficits may also be considered (Level C). Further study is needed regarding the yield of diagnostic testing in children with microcephaly. Neurology Microcephaly is an important neurologic sign but there is nonuniformity in the definition of microcephaly and inconsistency in the evaluation of affected children.1,2 Microcephaly is usually defined as a head circumference (HC) more than 2 SDs below the mean for age and gender.2,3 Some academics have advocated for defining severe microcephaly as an HC more than 3 SDs below the mean.4-7 Other than where specified, this parameter uses the usual definition of microcephaly. Recommended methods for HC measurement are described in appendix 2.If HC is normally distributed, 2.3% of children should by definition be microcephalic. However, published estimates for HC ϽϪ2 SD at birth are far lower, at 0.56% 8 and 0.54%. 9 The difference may be accounted for by a non-normal distribution, postnatal development of microcephaly, or incomplete ascertainment. Severe microcephaly would be expected Appendices e-1 through e-6 and references e1-e12 are available on the Neurology Web site at www.neurology.org.

Patients with HPE manifest a wide spectrum of clinical problems and neurologic dysfunction. The nature and severity of many of these problems can be predicted by specific neuroanatomic abnormalities found in HPE.

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