Polymicrogyria

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Polymicrogyria is characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. The name of this condition literally means too many (poly-) small (micro-) folds (-gyria) on the surface of the brain.

The features associated with polymicrogyria depend on the size and location of the affected area. When the condition affects one side of the brain, it is called unilateral polymicrogyria. When it affects both sides of the brain, it is called bilateral polymicrogyria.

Bilateral forms of polymicrogyria tend to cause more severe neurological problems than unilateral forms. The signs and symptoms that are associated with bilateral polymicrogyria can include developmental delays, intellectual disabilities, problems with speech and swallowing, and recurrent seizures that may be difficult or impossible to control with anti-seizure medications. The most severe form of the disorder, bilateral diffuse polymicrogyria, affects the entire brain.

The mildest form of polymicrogyria is called unilateral focal polymicrogyria. This form of the condition affects a small area on one side of the brain. It may cause neurological problems, such as mild seizures that can be controlled with medication.

Polymicrogyria may occur alone (isolated polymicrogyria) or with other brain abnormalities. It is also a feature of several genetic syndromes that affect multiple parts of the body, such as 22q11.2 deletion syndrome (DiGeorge syndrome), 1p36 deletion syndrome, Smith-Kingsmore syndrome, megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, Aicardi syndrome, and Zellweger spectrum disorder.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

In most people with polymicrogyria, the cause of the condition is unknown. However, researchers have identified several environmental and genetic factors that may contribute to the development of this disorder.

Environmental causes of polymicrogyria include certain infections during pregnancy, such as cytomegalovirus and Zika virus infections. A lack of oxygen to the developing fetus, which can occur when the placenta is not working properly (placental insufficiency), may also increase the risk of developing polymicrogyria. Having twins may reduce blood flow to the developing brain, which may also increase the risk of polymicrogyria.

Researchers are investigating the various genetic causes of polymicrogyria. The condition can result from deletions or rearrangements of genetic material from several different chromosomes. Additionally, changes in one of over 50 genes can cause either isolated polymicrogyria or polymicrogyria that occurs as part of a syndrome. Genetic changes that cause disease are called pathogenic variants.

Pathogenic variants in one gene, ADGRG1 (also known as GPR56), have been found to cause a severe form of the condition called bilateral frontoparietal polymicrogyria (BFPP). The ADGRG1 gene appears to be critical for normal brain development. The ADGRG1 gene variants that cause BFPP likely disrupt the normal movement of brain cells early in development. As a result, the brain forms too many small folds.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

It can be difficult to determine the cause and inheritance pattern of polymicrogyria. The condition can be inherited in different ways depending on the particular cause.

When BFPP is caused by pathogenic variants in the ADGRG1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

When polymicrogyria is part of a genetic syndrome, it follows the inheritance pattern of that syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Although the prevalence of polymicrogyria is unknown, it is one of the most common malformations of cortical development, which are malformations that affect the development of the outer surface of the brain (cerebral cortex).

Which doctor should you see?

The suggested department for discussing Polymicrogyria is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Polymicrogyria. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.