Полимикрогирия: түрлері, көріністері және генетикалық аспектілері

Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri (microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region of the brain or multiple regions. The time of onset has yet to be identified; however, it has been found to occur before birth in either the earlier or later stages of brain development. Early stages include impaired proliferation and migration of neuroblasts, while later stages show disordered post migration development. The symptoms experienced differ depending on what part of the brain is affected. There is no specific treatment to get rid of this condition, but there are medications that can control the symptoms such as seizures, delayed development or weakened muscles as some of the noted effects.

Significant technological advances have been made within the past few decades that have allowed more extensive studies to be made regarding syndromes from conditions such as polymicrogyria. Research, imaging, and analysis has shown that distribution of polymicrogyria does not always appear to be random, which revealed different types polymicrogyria. A summary of clinical manifestations of each syndrome can be found below, in the section labelled "Clinical presentation". The main patterns of polymicrogyria are: perisylvian (61%), generalised (13%), frontal (5%), and parasagittal parieto occipital (3%) and 11% is associated with gray matter heterotopia (grey matter is located in the white matter instead of usual location in the cerebral cortex).

BFP appears to be a symmetrical polymicrogyria that extends anteriorly from the frontal poles to the posterior precentral gyrus, and inferiorly to the frontal operculum. Patients who had polymicrogyria distribution similar to this also experienced similar symptoms including delayed motor and language developments, spastic hemiparesis or quadriparesis, and forms of mild intellectual disability.

BFPP was one of the first discovered forms of polymicrogyria to have a gene identified linking to the syndromes caused. This gene is called GPR56. Symmetrical distribution is also evident in this form, but more distinctly, patients with BFPP were found to have atrophy of the cerebellum and brain stem, as well as bilateral white matter abnormalities. BFPP is characterized by esotropia, global development delay, pyramidal signs, cerebral signs, and seizures. Esotropia is also known as dysconjugate gaze, and is a common feature of severe static encephalopathy. This differentiates BFPP from the other bilateral polymicrogyria syndromes.

BPP is similar to the other types of polymicrogyria in that it is usually symmetrical, but BPP can vary among patients. BPP is characterized by its location; the cerebral cortex deep in the sylvian fissures is thickened and abnormally infolded, as well as the sylvian fissures extending more posteriorly up to the parietal lobes and more vertically oriented. BPP has been classified into a grading system consisting of four different grades that describe the variations in severity:

The grades move from most severe (Grade 1) to least severe (Grade 4). Although BFPP was the first form of polymicrogyria to be discovered, BPP was the first form to be described and is also the most common form of polymicrogyria. The clinical characterizations of BPP "include pseudobulbar palsy with diplegia of the facial, pharyngeal and masticory muscles (facio pharyngo glosso masticatory paresis), pyramidal signs, and seizures."

BPOP is located in the parasagittal and mesial regions of the parieto occipital cortex. This form has been associated with IQ scores that range from average intelligence to mild intellectual disability, seizures, and cognitive slowing. The age of seizure onset has been found to occur anywhere from 20 months to 15 years, and in most cases the seizures were intractable (meaning hard to control). Apart from that, mutations in more than 30 genes have been associated with PMG. Association with the gene WDR62 (diffuse or asymmetric PMG) and SCN3A has also been identified, Other genes implicated are: GPR56 (Bilateral frontoparietal PMG), TUBB2B (anterior predominant PMG), NDE1 (Diffuse PMG), AKT3 (Bilateral perisylvian PMG), and PIK3CA (Bilateral perisylvian PMG). TUBB2B mutations are known to contribute to polymicrogyria either with or without congenital fibrosis or the external ocular muscles, as well as bilateral perisylvian. The gene GPR56 is a member of the adhesion G protein coupled receptor family and is directly related to causing Bilateral frontoparietal polymicrogyria, (BFPP) 6. Other genes in the G protein coupled receptor family have effects with this condition as well such as the outer brain development, but not enough is known to carry out all the research properly so the main focus is starting with the specific GR56 gene within this category. This malformation of the brain is a result of numerous small gyri taking over the surface of the brain that should otherwise be normally convoluted. This gene is currently under studies to help identify and contribute to the knowledge about this condition. It is studied to provide information on the causes along with insight into the mechanisms of normal cortical development and the regional patterning of the cerebral cortex using magnetic resonance imagine, MRI. Specifically found to polymicrogyria due to mutation of this gene are myelination defects. GPR56 is observed to be important for myelinations due to a mutation in this gene results in reduced white matter volume and signal changes as shown in MRI's. While the cellular roles of GPR56 in myelination remains unclear, this information will be used to further other studies done with this gene. Another gene that has been associated with this condition is GRIN1 and GRIN2B. These syndromes both have frontoparieto polymicrogyria as their anomalies. To ensure proper diagnosis, doctors thus can examine a patient through neuroimaging or neuropathological techniques. To view these microscopic characteristics, magnetic resonance imaging (MRI) is used. First physicians must distinguish between polymicrogyria and pachygyria. Pachygria leads to the development of broad and flat regions in the cortical area, whereas the effect of PMG is the formation of multiple small gyri. Underneath a computerized tomography (CT scan) scan, these both appear similar in that the cerebral cortex appears thickened. However, MRI with a T1 weighted inversion recovery will illustrate the gray white junction that is characterized by patients with PMG. The global developmental delay that affects 94% can also be mitigated in some patients with occupational, physical, and speech therapies. The important aspect to realize is PMG affects each patient differently and treatment options and mitigation techniques will vary. Many services are available to help, most children's hospitals can direct caregivers guidance where to get the information they need to seek assistance.

The incidences of PMG and its different forms are unknown. However, the frequency of cortical dysplasia in general has been estimated to be 1 in 2,500 newborns. In the largest series of PMG cases, the bilateral perisylvian pattern was the most common topological pattern (52% of cases) followed by the unilateral perisylvian pattern (9% of cases). Understanding about development, classification and localization of the disorder have greatly improved. For instance, localization of specific cortex regions affected by the disease was determined. This allowed for clinical symptoms of patients to be linked with localized cortex areas affected. A gene that was identified to be a contributor to bilateral frontoparietal polymicrogyria was GPR56.