Posterior Fossa in Primary Microcephaly: Relationships between Forebrain and Mid-Hindbrain Size in 110 Patients

Abstract

Microcephalies vary widely in clinical severity and in morphology. The purpose of this study is to determine the frequency of disproportion between the size of the cerebrum and the size of midbrain and hindbrain structures in infants and children with microcephaly, as analysis of such disproportions might aid understanding of these disorders and facilitate testing for specific genetic causes. The relative sizes of the forebrain, each component of the brain stem, and vermis and hemispheres of the cerebellum were analyzed visually on magnetic resonance (MR) images of 110 microcephalic patients. A disproportionally large cerebellum, compared with the cerebrum, was found in 50 cases (45.5%), a proportional cerebellum in 49 cases (44.5%), and a disproportionally small cerebellum in 11 cases (10%). Proportional cerebella were most common in mild (86%) and moderate (55%) microcephaly patients, whereas disproportionately large cerebella were most common in severe (57%) and moderate (32%) microcephaly. Disproportionately small cerebella were seen only in moderate (13%) and severe (9%) microcephaly. As genes are expressed at different times in cerebral and cerebellar development, it is postulated that analysis of relative cerebellar and brain stem size may be useful in the initial analysis of microcephaly by MR images both to categorize and to help determine likely genetic causes.

Developmental protein kinase C hyper-activation results in microcephaly and behavioral abnormalities in zebrafish

“…This notion also corresponds with the clinical investigations that children with ASD often bear multi-organ developmental problems with dominant dysfunction in the brain 20 , 56 . In addition, our findings that PKC hyper-activation primarily perturbed the growth of the forebrain and midbrain may partly explain the disproportionately affected brain regions in microcephaly, in which the impact on the cerebellum is not as big as that on the forebrain and midbrain 57 .…”