The making of individual differences
The making of individual differences

This free course is available to start right now. Review the full course description and key learning outcomes and create an account and enrol if you want a free statement of participation.

Free course

The making of individual differences

8.3 Lissencephaly

Lissencephaly, literally meaning ‘smooth brain’, is characterised by the absence of sulci and gyri, and by a four-layered cortex, instead of the usual six layers, with the majority of cortical neurons in layer four (Figure 22). Babies born with lissencephaly have a very poor prognosis; the disease proving lethal before their second birthday. Behaviourally, lissencephaly results in epilepsy, mental retardation, motor impairment and a general lack of developmental progress.

Figure 22
Figure 22 Magnetic resonance images of normal and lissencephalic brains. The four lissencephalic brains show a thickened cortex and fewer gyri than is normal

Lissencephaly results from a mutation in the LIS1 gene. (Note: the nomenclature used here is correct for human genes, e.g. LIS1, and their products, e.g. LIS1P, and differs from the nomenclature used for Drosophila in Section 6.4.) A mutant form of this gene produces a non-functioning protein, which is lethal very early in prenatal development when it occurs on both chromosomes, i.e. when both alleles are defective. In this case the genome is said to be homozygous for it. However, in the heterozygous condition, where both forms are present, a certain amount of development occurs and it has been possible to establish the precise role of LIS1 using heterozygous knockout mice. Heterozygous mice show cortical disorganisation consistent with disordered neuronal migration.

During the development of the brain, neurons are born at the ventricular surface, where brain tissue meets the cerebrospinal fluid of the ventricles. Newly born neurons (neuroblasts) move away from the banks of the ventricles towards the outer surface (the pial surface) of the brain. In terms of the number of items (neuroblasts) moving, this is an unimaginably vast migration. The movement of the neuroblasts involves a number of activities, one of which ensures that the nucleus stays within its cell, and doesn't get left behind. This is nucleokinesis. The protein product of LIS1, LIS1P, pulls the nucleus along and so is important in nucleokinesis. In the homozygous mutant condition, the protein is absent/defective and there is nothing to pull the nucleus along, so nucleokinesis and hence cell migration, cannot occur, resulting in the early death of the organism. In the heterozygous condition, some LIS1P is made and so some nucleokinesis can occur, though the exact extent depends on the amount of LIS1P produced and which other genes are present.

Lissencephaly is a congenital disease, meaning simply that the symptoms of the disease are present at birth. In contrast to Wilson's disease, lissencephaly is untreatable. This is because intervention would need to happen more or less at conception, be continuous throughout development and target neuroblasts at the ventricular surface.

Although relatively rare, more than 25 different syndromes with abnormal neuronal migrations have been described in humans. Some authorities suggest they account for up to one-third of all cases of severe epilepsy.

SD226_1

Take your learning further

Making the decision to study can be a big step, which is why you'll want a trusted University. The Open University has 50 years’ experience delivering flexible learning and 170,000 students are studying with us right now. Take a look at all Open University courses.

If you are new to university level study, find out more about the types of qualifications we offer, including our entry level Access courses and Certificates.

Not ready for University study then browse over 900 free courses on OpenLearn and sign up to our newsletter to hear about new free courses as they are released.

Every year, thousands of students decide to study with The Open University. With over 120 qualifications, we’ve got the right course for you.

Request an Open University prospectus