Clinical and brain imaging heterogeneity of severe microcephaly

Microcephaly may be present at birth or develop postnatally. Classification according to the genetic cause cannot always predict the severity of the clinical course. The aim of this research was to group a large cohort of patients with primary microcephaly into more discrete subtypes, to optimize assessment of the patients based on their clinical and brain imaging findings. Medical records and brain images were reviewed for 4442 patients with brain malformations diagnosed and treated over 24 years and identified 247 patients classified as having microcephaly with simplified gyri alone or in association with additional brain abnormalities. For each case, clinical records were retrospectively reviewed for consanguinity, positive family history, sex, associated anomalies, and cranial magnetic resonance imaging. A subset (n = 12) of representative patients with the most complete available data was studied in greater detail, to define the most common subtypes and clinical presentations. Overall, four relatively common brain imaging presentations were identified, involving abnormalities in the gyral pattern, extra-axial space, and small size of the brainstem and cerebellum. Classifying patients with microcephaly according to brain imaging findings could enable more accurate counseling of the families with regard to prognosis.