30 November 2023
New brain malformation identified
Published online 28 August 2012
Researchers describe a devastating genetic development disorder.
A debilitating genetic condition in which patients have an enlarged midbrain has been identified by a team of researchers led by Maha Zaki of the National Research Centre in Cairo.
Patients in the study suffered severe cognitive impairments, an acute form of cerebral palsy called spastic quadriparesis, and epileptic seizures accompanied, in some cases, by eye abnormalities, deterioration of heart muscles, and club foot.
Zaki, a biochemist at the centre, and her colleagues studied three unrelated consanguineous Egyptian families and identified six cases of the condition which they have named diencephalic-mesencephalic junction dysplasia (DMJD). They found the common factor in the previously undiagnosed disorder was an abnormally formed midbrain.
Structural MRI scans revealed that the midbrain in all six patients was elongated and butterfly shaped in cross section. The rest of the brain was under-developed.
In some subjects, the cerebral ventricles were slightly enlarged and the cerebral cortex smaller than usual. In others the ventricles were significantly enlarged, most of the cortex missing, and the corpus callosum, which connects the left and right hemispheres, was absent.
Diffusion tensor imaging, an MRI technique, performed on two of the patients showed that the corticospinal tract, a large fibre tract that connects the motor cortex to motor neurons in the spine controlling voluntary movement had not developed at all.
During normal fetal development, the region that forms the brain divides into three discrete compartments, which go on to form the forebrain, midbrain and hindbrain. Each of these becomes further subdivided, and the boundaries between them act as vital signalling centres that instruct the development of the tissues on either side. Boundary formation is controlled by complex mechanisms involving dozens of genes.
DMJD occurs when the boundary between the mesencephalon - the compartment that becomes the midbrain - and the diencephalon - that becomes the thalamus and hypothalamus - is positioned wrongly during early development. It is an autosomal recessive disorder, caused by the inheritance of two mutated copies of a gene, but the gene that causes it is still unidentified.
- Zaki, M. S., et al. Diencephalic–mesencephalic junction dysplasia: a novel recessive brain malformation. Brain, 135; 2416-2427 (2012).