Polymicrogyria (PMG), is a condition characterized by abnormal development of the brain before birth. While a baby is still in the womb, neurons are migrating to where they are supposed to go. For some reason, the neurons become disorganized and land in the wrong places. The surface of the brain normally has many ridges or folds, called gyri. In individuals born 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) in the surface of the brain. These small folds do not process the information it receives like a normally formed brain. This causes problems with functioning in the body much like how the effects of a stroke can affect the brain. The impairments that are seen as a result of PMG depend on what part of the brain is involved and how severe the deformity is.
There are several different forms of PMG (see the RESOURCES tab for more information). Even though multiple individuals may be diagnosed with the same form, PMG affects everyone differently. Common problems associated with PMG in general are: swallowing and speech difficulties, reflux, seizures of varying degrees (about 90% are affect with seizures at some point in their lives), development delays, lack of muscle coordination, impaired cognition of varying degrees and cerebral palsy, but there can be many others.
For some, PMG can also cause problems with vision, cognition, hearing, breathing and maintaining body temperature. Sometimes it comes with other diagnoses such as cerebral palsy, epilepsy, hydrocephalus, macrocephaly, microcephaly (certainly not an all-inclusive list). It is important to note that many cases are mild enough to go undiagnosed and the individual is labeled as “developmentally delayed” or having a “seizure disorder” or “cerebral palsy.” It is imperative to take the extra step to find out why an individual is being labeled with these disorders and have them undergo an MRI (magnetic resonance imaging exam) to look at the brain. PMG, at the present time, can only be diagnosed through MRI results. It is also important to note that a specialized radiologist who knows what they are looking for should read the results of the MRI. Currently, many people are falling through the cracks and being misdiagnosed, especially when their symptoms are mild. This results in delayed or reduced access to medical interventions and therapies during critical stages of brain development, which could impact future prognosis.
What Causes Polymicrogyria?
Polymicrogyria can result from both genetic and environmental etiologies. It may occur as an isolated event, or as a symptom or part of other brain abnormalities. Many years of data collection and research have led experts to believe that the most common cause of PMG is related to a prenatal infection from a virus called Cytomegalovirus, also known as CMV. Polymicrogyria has also been linked to the Zika Virus, which is the most common cause of PMG in Brazil and South America (see the RESOURCES tab for more information on both CMV and the Zika Virus).
Recent studies have used the term “PMG” to refer to several different development disorders or birth defects of the brain that all have an irregular appearance of the brain surface in common. They have split “PMG” into different categories; classic PMG, Cobblestone Malformation, Tubulinopathy-associated dysgyria and other rare patterns. While rare, almost 50 genes have been identified and associated with Polymicrogyria or PMG-like malformations, which fall into several groups listed below:
- PMG GENES (all very rare) – PAX6, FOXP2, BICD2, EOMES (TBR2), WDR62, NDE1, CEP135, PI4KA
- TUBULINOPATHY GENES – TUBA1A, TUBA8, TUBB2B, TUBB, TUBB3, DYNC1H1, KIF5C, KATNB1
- WARBURG MICRO SYNDROME GENES – RAB3GAP1, RAB3GAP2, RAB18, TBC1D20
- COBBLESTONE MALFORMATION GENES WITH CONGENITAL MUSCULAR DYSTRPHY PLUS – AG1, POMT1, POMT2, POMGnT1, FKTN, FKRP, LARGE, B3GALNT2, B3GNT1, GALNT2, GTDC2, ISPD, TMEM5
- COBBLESTONE MALFORMATION GENES OTHER – LAMA2, LAMB1, LAMC3, GPR56/ADGRG1, COL3A1, SRD5A3, ATP6V0A2, SNAP29
- BRAIN OVERGROWTH AND PMG GENES – PIK3CA, PIK3R2, PTEN, AKT3, MTOR, CCND2
In addition, PMG has been seen with two relatively common chromosome deletion syndromes: deletion 1p36.3, also known as Monosomy 1p36 and deletion 22q11.2, also known as DiGeorge Syndrome (see the RESOURCES tab for more information about these syndromes).
As research, MRI’s and other imaging technology advance, so do the numbers of individuals who are being diagnosed with PMG. Unfortunately, there are still many people with less severe cases of PMG that may go undiagnosed. Often, PMG is not found unless there is a significant event in the individual’s life that leads to an MRI. But even with an MRI, it may still go undiagnosed unless a specialized radiologist reads the MRI.
It is difficult to make a predictable prognosis because each individual is very unique in their presentation of this disorder.
Why is it important to get a diagnosis?
The answer to that question is multi-fold:
- Without a diagnosis, many individuals are not afforded proper medical care and other benefits.
- Without accurate statistical data, the number of cases seem smaller and therefore funding for research and treatment is poor.
- As more people are diagnosed, the public becomes more aware of their needs.
- Early diagnosis is CRITICAL – delay of diagnosis often means that therapy and treatment during the “golden era of childhood development” (the first three years) is missed, leaving the child with a greater chance of permanent loss of developmental goals.
- EVERYONE deserves to have an answer!
How is Polymicrogyria treated?
Treatment and management of PMG depend on the needs of the individual. Commonly used, but not limited too, are physical therapy for gross motor impairment, orthotic devices and surgery for those with spastic motor impairment. Speech therapy is widely used for language and feeding impairment. Augmentative and alternative communication devices are also commonly used to aide in speech deficits. Occupational therapy is used for fine motor difficulties and antiepileptic drugs are used to treat and control seizure.
