Polymicrogyria- how do I investigate further?

This 2 year old child came in with global developmental delay and microcephaly. Antenatal and perinatal period had been unremarkable. There was no dysmorphism, nor organomegaly or other malformation.

The MRI brain was reported to have right sided pachygyria over the parietal-occipital cortex, polymicrogyria in the perisylvian region also more on the right. There were also some white matter abnormalities in the underlying subcortical regions.

Questions which I needed to answer were- is this acquired or genetic? How do I investigate further?

New recommendations for the diagnostic work-up of malformations of cortical development (MCD) were recently published in Nature Reviews Neurology in September 2020 https://doi.org/10.1038/s41582-020-0395-6

Some useful tips this article gave are as follows:

Focal versus generalised abnormalities do not reliably separate the acquired versus genetic disorders!

Polymicrogyria and pachygyria are sometimes confused. A simple tip is that pachygyria will usually have a thick cortex while the polymicrogyric cortex is thinner.

Always look at the parasaggital image to scrutinise for polymicrogyria. The abnormal posterior extension of the sylvan fissure and sulcal branching can be a real give away.

 

 Another term to remember is 'dysgyria'. This means an abnormal gyral pattern which doesn't fit into the classical malformations of cortical development. Often a clue for the tubulinopathies.

Polymicrogyria or microcephaly must always prompt an assessment for possible intrauterine infections like CMV, TORCH and Zika. The presence of white matter changes and calcification is a clue to congenital CMV.

Intra-uterine vascular disruptive events and twinning ( probably due to hypo perfusion in the twin to twin transfusion syndrome) are also important causes of polymicrogyria.

Chromosomal microarray is the first genetic test to be used for all MCD followed if necessary by exome sequencing. 36% of patients with periventricular nodular heterotropia will have an abnormal CMA and the number is 9% for those with polymicrogyria alone.

A genetic cause of polymicrogyria is most likely to be found in children with macrocephaly- especially the PI3K-AKT-MTOR related disorders.

Metabolic disorders like Zellwegers syndrome of the d-bifunctional protein deficiency can also be associated with polymicrogyria. These children are sicker and the dysmorphism, hepatomegaly and leukoencephalopaty of Zellwegger's is also a clue.