The diagnosis of PMG is merely descriptive and is not a disease in itself, nor does it describe the underlying cause of the brain malformation.

Polymicrogyria may be just one piece of a syndrome of developmental abnormalities, because children born with it may suffer from a wide spectrum of other problems, including global developmental disabilities, mild to severe mental retardation, motor dysfunctions including speech and swallowing problems, respiratory problems, and seizures. Though it is difficult to make a predictable prognosis for children with the diagnosis of PMG, there are some generalized clinical findings according to the areas of the brain that are affected.

- Bilateral frontal polymicrogyria (BFP) – Cognitive and motor delay, spastic quadriparesis, epilepsy

- Bilateral frontoparietal polymicrogyria (BFPP) – Severe cognitive and motor delay, seizures, dysconjugate gaze, cerebellar dysfunction

- Bilateral perisylvian polymicrogyria (BPP) – Pseudobulbar signs, cognitive impairment, epilepsy, some with arthrogryposis or lower motor neuron disease

- Bilateral parasagittal parieto-occipital polymicrogyria (BPPP) – Partial seizures, some with mental retardation

- Bilateral generalized polymicrogyria (BGP) – Cognitive and motor delay of variable severity, 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 mental retardation, 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).

Subcortical heterotopia form as distinct nodes in the white matter, "focal" indicating specific area. In general, patients present fixed neurologic deficits and develop partial epilepsy between the ages of 6 and 10. The more extensive the subcortical heterotopia, the greater the deficit; bilateral heterotopia are almost invariably associated with severe developmental delay or mental retardation. The cortex itself often suffers from an absence of gray matter and may be unusually thin or lack deep sulci. Subependymal heterotopia are frequently accompanied by other structural abnormalities, including an overall decrease in cortical mass. Patients with focal subcortical heterotopia have a variable motor and intellectual disturbance depending on the size and site of the heterotopion.

Various degrees of intensity and locations of epilepsy are associated with malformations of cortical development. Researchers suggest that approximately 40% of children diagnosed with drug-resistant epilepsy have some degree of cortical malformation.

Lissencephaly (to which pachygyria is most closely linked) is associated with severe mental retardation, epilepsy, and motor disability. Two characteristics of lissencephaly include its absence of convolutions (agyria) and decreased presence of convolutions (pachygyria). The types of seizures associated with lissencephaly include:

- persisting spasms

- focal seizures

- tonic seizures

- atypical seizures

- atonic seizures

Other possible symptoms of lissencephaly include telecanthus, estropia, hypertelorism, varying levels of mental retardation, cerebellar hypoplasia, corpus callosum aplasia, and decreased muscle tone and tendon reflexes. Over 90% of children affected with lissencephaly have seizures.

Patients with subcortical band heterotopia (another disorder associated with pachygyria) typically have milder symptoms and their cognitive function is closely linked to the thickness of the subcortical band and the degree of pachygyria present.

Gray matter heterotopia (singular "heterotopion") is a neurological disorder caused by clumps of grey matter (ectopic nodules of neurons) located in the wrong part of the brain. It is characterized as a type of cortical dysplasia. The neurons in heterotopia appear to be normal, except for their mislocation; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound; the condition is occasionally discovered by brain imaging performed for an unrelated problem and has no apparent ill effect on the patient. At the other extreme, heterotopia can result in severe seizure disorder, loss of motor skills, and mental retardation. Fatalities are practically unknown, other than the death of unborn male fetuses with a specific genetic defect.

Pachygyria (from the Greek "pachy" meaning "thick" or "fat" gyri) is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation. Infantile spasms are common in affected children, as is intractable epilepsy.

BFPP is a cobblestone-like cortical malformation of the brain. Disruptions of cerebral cortical development due to abnormal neuronal migration and positioning usually lead to cortical disorders, which includes cobblestone lissencephaly. Cobblestone lissencephaly is typically seen in three different human congenital muscular dystrophy syndromes: Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease. In cobblestone lissencephaly, the brain surface actually has a bumpy contour caused by the presence of collections of misplaced neurons and glial cells that have migrated beyond the normal surface boundaries of the brain. Sometimes regions populated by these misplaced cells have caused a radiologic misdiagnosis of polymicrogyria. However, the presence of other abnormalities in these cobblestone lissencephaly syndromes, including ocular anomalies, congenital muscular dystrophy, ventriculomegaly, and cerebellar dysplasia, usually distinguishes these disorders from polymicrogyria. There are no anatomopathologic studies that have characterized the pattern of cortical laminar alterations in patients with GPR56 gene mutations, but it has been suggested that the imaging characteristics of BFPP, including myelination defects and cerebellar cortical dysplasia, are reminiscent of those of the so-called cobblestone malformations (muscle-eye-brain disease and Fukuyama congenital muscular dystrophy) that are also associated with N-glycosylation defects in the developing brain.

Lissencephaly ("smooth brain") is the extreme form of pachygyria. In lissencephaly, few or no sulci are seen on the cortical surface, resulting in a broad, smooth appearance to the entire brain. Lissencephaly can be radiologically confused with polymicrogyria, particularly with low-resolution imaging, but the smoothness and lack of irregularity in the gray-white junction, along with markedly increased cortical thickness, distinguishes lissencephaly.

GPR56 mutation also can cause a severe encelphalopathy which is associated with electro clinical features of the Lennox-Gastaut syndrome. Lennox-Gastaut syndrome can be cryptogenic or symptomatic, but the symptomatic forms have been associated with multiple etiologies and abnormal cortical development. BFPP caused by GPR56 mutations is a representation of a malformation of cortical development that causes Lennox-Gastaut Syndrome.

Polymicrogyria usually gets misdiagnose with pacygyria so therefore it needs to be distinguished from pachygyria. Pachygyria is a distinct brain malformation in which the surface folds are excessively broad and sparse. Pachygyria and polymicrogyria may look similar on low-resolution neuroimaging such as CT because the cortical thickness can appear to be increased and the gyri can appear to be broad and smooth in both conditions. This is why higher resolution neuroimaging are needed such as an MRI.

Patients come to clinical attention early in life (usually at birth or within the first few months), with a firm subcutaneous nodule at bridge of nose, or as a polypoid mass within the nasal cavity, or somewhere along the upper border of the nasal bow. If the patient presents with an intranasal mass, there may be obstruction, chronic rhinosinusitis, or nasal drainage. If there is a concurrent cerebrospinal fluid (CSF) leak, then an encephalocele is much more likely.

This lesion is separated into two types based on the anatomic site of presentation:

1. Extranasal (60%): Subcutaneous bridge of nose

2. Intranasal (30%): Superior nasal cavity

3. Mixed (10%): Subcutaneous tissues and nasal cavity (larger lesions)

Microlissencephaly with intermediate cortex and abrupt anteroposterior gradient

There are different tests or methods used to determine GPR56 expression or visuals of the brain to analyze the specific sections that are affected. These tests for example, using animals such as mice, RNAi, Behavioral assay, Electron microscopy, CT scan, or MRI demonstrate different results that concludes an affected BFPP patient. MRI's reveal either irregularity to the cortical surface suggestive of multiple small folds or an irregular, scalloped appearance of the gray matter-white matter junction.

Neuroimaging The diagnosis of polymicrogyria is typically made by magnetic resonance imaging (MRI) since computed tomography (CT) and other imaging methods generally do not have high enough resolution or adequate contrast to identify the small folds that define the condition. The cerebral cortex often appears abnormally thick as well because the multiple small gyri are fused, infolded, and superimposed in appearance.

Neuropathology Gross neuropathologic examination reveals a pattern of complex convolutions to the cerebral cortex, with miniature gyri fused and superimposed together, often resulting in an irregular brain surface. The cortical ribbon can appear excessively thick as a result of the infolding and fusion of multiple small gyri.

Microscopic examination demonstrates that the cerebral cortex is in fact abnormally thin and has abnormal lamination; typically the cortex is unlayered or has four layers, in contrast to the normal six layers. The most superficial layers between adjacent small gyri appear fused, with the pia (layer of the meninges) bridging across multiple gyri. Prenatal diagnosis for BFPP is also available for pregnancies at risk if the GPR56 mutations have been identified in an affected family member.

Microlissencephaly Type B or Barth microlissencephaly syndrome: is a microlissencephaly with thick cortex, severe cerebellar and brainstem hypoplasia. The Barth-type of MLIS is the most severe of all the known lissencephaly syndromes.

This phenotype consists of polyhydramnios (probably due to poor fetal swallowing), severe congenital microcephaly, weak respiratory effort, and survival for only a few hours or days. Barth described two siblings with this type as having a very low brainweight, wide ventricles, a very thin neopallium, absent corpus callosum and absent olfactory nerve.

Nasal glial heterotopia refers to congenital malformations of displaced normal, mature glial tissue, which are no longer in continuity with an intracranial component. This is distinctly different from an encephalocele, which is a herniation of brain tissue and/or leptomeninges, that develops through a defect in the skull, where there is a continuity with the cranial cavity.

CGCG lesions are found more commonly in the anterior of the maxilla and the mandible in younger people (before age 20). They are characterized by large lesions that expand the cortical plate and can resorb roots and move teeth. They are composed of multi-nucleated giant cells. CGCG has a slight predilection for females.

Radiographically :

It appears as multilocular radiolucencies of bone.The margin of the lesion has scalloped appearance and is well demarcated. Resorption and divergence of roots is also seen.

There are two types of CGCG's, non-aggressive and aggressive. The former has a slow rate of growth and thus less likely to resorb roots and perforate the cortical plate. The aggressive form has rapid growth and thus is much more likely to resorb roots and perforate the cortical plate. It also has a high rate for recurrence and can be painful and cause paresthesia.

Differential diagnosis to include: odontogenic keratocyst (OKC), ameloblastoma, odontogenic myxoma, hemangioma, central odontogenic fibroma, hyperparathyroid tumor, and cherubism.

Retinal lesions, called astrocytic hamartomas (or "phakomas"), which appear as a greyish or yellowish-white lesion in the back of the globe on the ophthalmic examination. Astrocytic hamartomas can calcify, and they are in the differential diagnosis of a calcified globe mass on a CT scan.

Nonretinal lesions associated with TSC include:

- Coloboma

- Angiofibromas of the eyelids

- Papilledema (related to hydrocephalus)

Atypical tuberous myxedema, also known as Jadassohn–Dosseker syndrome, is thought to represent a pure nodular of lichen myxedematosus.

Some form of dermatological sign is present in 96% of individuals with TSC. Most cause no problems, but are helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin abnormalities include:

- Facial angiofibromas ("adenoma sebaceum"): A rash of reddish spots or bumps, which appears on the nose and cheeks in a butterfly distribution, they consist of blood vessels and fibrous tissue. This potentially socially embarrassing rash starts to appear during childhood and can be removed using dermabrasion or laser treatment.

- Periungual fibromas: Also known as Koenen's tumors, these are small fleshy tumors that grow around and under the toenails or fingernails and may need to be surgically removed if they enlarge or cause bleeding. These are very rare in childhood, but common by middle age. They are generally more common on toes than on fingers, develop at 15–29 years, and are more common in women than in men. They can be induced by nail-bed trauma.

- Hypomelanic macules ("ash leaf spots"): White or lighter patches of skin, these may appear anywhere on the body and are caused by a lack of melanin. They are usually the only visible sign of TSC at birth. In fair-skinned individuals, a Wood's lamp (ultraviolet light) may be required to see them.

- Forehead plaques: Raised, discolored areas on the forehead

- Shagreen patches: Areas of thick leathery skin that are dimpled like an orange peel, and pigmented, they are usually found on the lower back or nape of the neck, or scattered across the trunk or thighs. The frequency of these lesions rises with age.

- Other skin features are not unique to individuals with TSC, including molluscum fibrosum or skin tags, which typically occur across the back of the neck and shoulders, "café au lait" spots or flat brown marks, and poliosis, a tuft or patch of white hair on the scalp or eyelids.

Central giant-cell granuloma (CGCG) is a benign condition of the jaws. It is twice as likely to affect women and is more likely to occur in 20- to 40-year-old people. Central giant-cell granulomas are more common in the mandible and often cross the midline.

Choristomas, forms of heterotopia, are closely related benign tumors, found in abnormal locations.

It is different from hamartoma. The two can be differentiated as follows: a hamartoma is disorganized overgrowth of tissues in their normal location, (eg, Peutz-Jeghers polyps) while a choristoma is normal tissue growth in an abnormal location (e.g., gastric tissue located in distal ileum in Meckel diverticulum).

Cortical pseudolaminar necrosis, also known as cortical laminar necrosis and simply laminar necrosis, is the (uncontrolled) death of cells in the (cerebral) cortex of the brain in a band-like pattern, with a relative preservation of cells immediately adjacent to the meninges.

It is seen in the context of cerebral hypoxic-ischemic insults, i.e. strokes.

Focal nodular hyperplasia's most recognizable gross feature is a central stellate scar seen in 60–70% of cases. Microscopically, a lobular proliferation of bland-appearing hepatocytes with a bile ductular proliferation and malformed vessels within the fibrous scar is the most common pattern. Other patterns include telangiectatic, hyperplastic-adenomatous, and lesions with focal large-cell dysplasia. Rarely, these lesions may be multiple or can occur as part of a syndrome with hemangiomas, epithelioid hemangioendothelioma, hepatic adenomas, fibrolamellar hepatocellular carcinoma, vascular malformations of the brain, meningiomas, and/or astrocytomas.

Often, this disease evolves from a precursor lesion, usually a dysplastic nevus. Otherwise it arises in previously normal skin. A prolonged radial growth phase, where the lesion remains thin, may eventually be followed by a vertical growth phase where the lesion becomes thick and nodular. As the risk of spread varies with the thickness, early SSM is more frequently cured than late nodular melanoma.

The microscopic hallmarks are:

- Large melanocytic cells with nest formation along the dermo-epidermal junction.

- Invasion of the upper epidermis in a pagetoid fashion (discohesive single cell growth).

- The pattern of rete ridges is often effaced.

- Invasion of the dermis by atypical, pleomorphic melanocytes

- Absence of the 'maturation' typical of naevus cells

- Mitoses

Trichoblastomas are a cutaneous condition characterized by benign neoplasms of follicular germinative cells. Trichoblastic fibroma is a designation used to characterize small nodular trichoblastomas with conspicuous fibrocytic stroma, sometimes constituting over 50% of the lesion.

There are two forms (also referred to as "classifications") of FCMS; bilateral and unilateral. The bilateral form is most common (also referred to as the "classical form") and is caused by the formation of lesions on both sides of the anterior or posterior region of the operculum. In contrast, the unilateral form is rare and is caused by the formation of lesions on one side of the anterior or posterior region of the operculum. Lesions located in the anterior regions of the operculum are associated with motor deficits and anarthria, a total absence of the ability to form speech or language. Lesions located in the posterior regions of the operculum are associated with parietal opercular functions. The two classifications of FCMS were established based on the location of the lesion, stroke, and trauma affecting the brain. Classifying FCMS based solely upon lesions yields five specific subtypes of FCMS currently known to fall into the bilateral and unilateral categories:

- Bilateral anterior opercular syndrome (lesion in both the anterior or in the frontal operculum)

- Opercular-subopercular syndrome (lesions in the opercular cortex on one side and the subopercular lesion in the contralateral side).

- Subopercular syndrome (lesions in the subcortical corticobulbar projections only).

- Unilateral anterior syndrome involving the frontal operculum.

- Posterior syndrome involving the junction between the frontal and the parietal lobe of the operculum.

The bilateral form of FCMS ("also known as facio-labio-pharyngo-glosso-laryngo-brachial paralysis)" is consistent with the classic presentation of bilateral corticobulbar involvement. It is characterized by well-preserved automatic and reflex movements. It is caused by lesions in the cortical or subcortical region of the anterior opercular area surrounding the insula forming the gyri of the frontal, temporal, and parietal lobes.

Focal nodular hyperplasia (FNH) is a benign tumor of the liver (hepatic tumor), which is the second most prevalent tumor of the liver (the first is hepatic hemangioma). It is usually asymptomatic, rarely grows or bleeds, and has no malignant potential. This tumour was once often resected because it was difficult to distinguish from hepatic adenoma, but with modern multiphase imaging is usually now diagnosed by strict imaging criteria and not resected.