Movements of the eyes left to right.

Little or no movement in the arms or legs.

Respiratory troubles/problems.

The diagnosis of PMD is often first suggested after identification by magnetic resonance imaging (MRI) of abnormal white matter (high T2 signal intensity, i.e. T2 lengthening) throughout the brain, which is typically evident by about 1 year of age, but more subtle abnormalities should be evident during infancy. Unless there is a family history consistent with sex-linked inheritance, the condition is often misdiagnosed as cerebral palsy. Once a "PLP1" or "GJA12" mutation is identified, prenatal diagnosis or preimplantation genetic diagnostic testing is possible.

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.

Sturge–Weber syndrome is usually manifested at birth by a port-wine stain on the forehead and upper eyelid of one side of the face, or the whole face. The birthmark can vary in color from light pink to deep purple and is caused by an overabundance of capillaries around the ophthalmic branch of the trigeminal nerve, just under the surface of the face. There is also malformation of blood vessels in the pia mater overlying the brain on the same side of the head as the birthmark. This causes calcification of tissue and loss of nerve cells in the cerebral cortex.

Neurological symptoms include seizures that begin in infancy and may worsen with age. Convulsions usually happen on the side of the body opposite the birthmark which vary in severity. There may also be muscle weakness on the side of the body opposite the birthmark.

Some children will have developmental delays and cognitive delays; about 50% will have glaucoma (optic neuropathy often associated with increased intraocular pressure), which can be present at birth or develop later. Glaucoma can be expressed as leukocoria, which should include also further evaluation for retinoblastoma. Increased pressure within the eye can cause the eyeball to enlarge and bulge out of its socket (buphthalmos).

Sturge–Weber syndrome rarely affects other body organs.

The specific and familial association of BIFE and PKC defines a novel clinical entity : the infantile convulsions and choreoathetosis syndrome. The first observation was made in four families where children were affected with nonfebrile convulsions at age 3–12 months.Partial epileptic seizures started with a psychomotor arrest and a deviation of the head and eyes to one side, followed inconstantly by unilateral jerks.In some cases, seizures generalized secondarily. None of the interictal electroencephalograms showed epileptiform abnormalities, and magnetic-resonance imaging were normal. These convulsions had a favorable outcome. At 5–8 years of age affected children developed abnormal movements. They presented with twisting movements of the hands of a reptilian type when stressed or embarrassed. They also developed jerky movements of the legs after running. Initially, abnormal movements were intermediate in speed between quick and slow, typical of paroxysmal choreoathetosis. Combinations of abnormal movements involving the arms, legs, trunk and occasionally the head were observed. The attacks lasted only a few minutes, occurring with a frequency of 5-30 episodes per day and were not accompanied by unconsciousness. In all patients, abnormal movements disappeared at 25–30 years of age without any treatment. Since the first report similar clinical presentations have been published which confirm the specificity of the ICCA syndrome.

Dennie–Marfan syndrome is a syndrome in which there is association of spastic paraplegia of the lower limbs and mental retardation in children with congenital syphilis. Both sexes are affected, and the onset of the disease can be acute or insidious, with slow progression from weakness to quadriplegia. Epilepsy, cataract, and nystagmus may be also be found.

The syndrome was described by Charles Clayton Dennie in 1929, and Antoine Marfan in 1936.

Mild prenatal growth retardation

Moderate postnatal growth retardation

Mild to severe developmental delay

Severely impaired speech

Seizures

Microcephaly

Sparse hair

Progressive skin wrinkling

Thick, anteverted alae nasi

Long and broad philtrum

Large mouth

Thin upper and thick lower vermilion

Progressive prominence of distal phalanges

Progressive prominence of inter-phalangeal joints

Short metacarpals–metatarsals

Sturge–Weber syndrome or Sturge–Weber–Krabbe disease, sometimes referred to as encephalotrigeminal angiomatosis, is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma, seizures, mental retardation, and ipsilateral leptomeningeal angioma (cerebral malformations and tumors). Sturge Weber Syndrome can be classified into three different types. Type 1 includes facial and leptomeningeal angiomas as well as the possibility of glaucoma or choroidal lesions. Normally, only one side of the brain is affected. This type is the most common. Type 2 involvement includes a facial angioma (port wine stain) with a possibility of glaucoma developing. There is not any evidence of brain involvement. Symptoms can show at any time beyond the initial diagnosis of the facial angioma. The symptoms can include glaucoma, cerebral blood flow abnormalities and headaches. More research is needed on this type of Sturge Weber Syndrome. Type 3 has leptomeningeal angioma involvement exclusively. The facial angioma is absent and glaucoma rarely occurs. This type is only diagnosed via brain scan.

Sturge-Weber is an embryonal developmental anomaly resulting from errors in mesodermal and ectodermal development. Unlike other neurocutaneous disorders (phakomatoses), Sturge-Weber occurs sporadically (i.e., does not have a hereditary cause). It is caused by a somatic activating mutation occurring in the GNAQ gene. Radiological findings will show tram track calcifications on CT, bilaterally.

SFMS affects the skeletal and nervous system. This syndrome's external signs would be an unusual facial appearance with their heads being slightly smaller and unusually shaped, a narrow face which is also called dolichocephaly, a large mouth with a drooping lower lip that are held open, protruding upper jaw, widely spaced upper front teeth, an underdeveloped chin, cleft palate and exotropied-slanted eyes with drooping eyelids.

Males who have SFMS have short stature and a thin body build. Also skin is lightly pigmented with multiple freckles. They may have scoliosis and chest abnormalities.

Affected boys have reduced muscle tone as infants and young children. X-rays sometimes show that their bones are underdeveloped and show characteristics of younger bones of children. Boys usually under the age of 10 have reduced muscle tone but later, patients with SFMS over the age of 10 have increased muscle tone and reflexes that cause spasticity. Their hands are short with unusual palm creases with short, shaped fingers and foot abnormalities are shortened and have fused toes and usually mild.

They have an absent of a spleen and the genitals may also show undescended testes ranging from mild to severe that leads to female gender assignment.

People who have SFMS have severe mental retardation. They are sometimes restless, behavior problems, seizures and severe delay in language development. They are self-absorbed with reduced ability to socialize with others around them. They also have psychomotor retardation which is the slowing-down of thoughts and a reduction of physical movements. They have cortical atrophy or degeneration of the brain's outer layer. Cortical atrophy is usually founded in older affected people.

Symptoms of holoprosencephaly range from mild (no facial/organ defects, anosmia, or only a single central incisor) to moderate to severe (cyclopia).

There are four classifications of holoprosencephaly.

- Alobar holoprosencephaly, the most serious form, in which the brain fails to separate, is usually associated with severe facial anomalies, including lack of a nose and the eyes merged to a single median structure, see Cyclopia

- Semilobar holoprosencephaly, in which the brain's hemispheres have somewhat divided, is an intermediate form of the disease.

- Lobar holoprosencephaly, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly, the patient's brain may be nearly normal.

- Syntelencephaly, or middle interhemispheric variant of holoprosencephaly (MIHV), in which the posterior frontal lobe and the parietal lobe are not properly separated, but the rostrobasal forebrain properly separates; it is possible that this is not a variant of HPE at all, but is currently classified as such.

- Agenesis of the corpus callosum, in which there is a complete or partial absence of the corpus callosum. It occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally, typically during pregnancy. The fibers that would otherwise form the corpus callosum become longitudinally oriented within each hemisphere and form structures called Probst bundles.

Holoprosencephaly consists of a spectrum of defects or malformations of the brain and face. At the most severe end of this spectrum are cases involving serious malformations of the brain, malformations so severe that they often cause miscarriage or stillbirth. At the other end of the spectrum are individuals with facial defects which may affect the eyes, nose, and upper lip - and normal or near-normal brain development. Seizures and mental retardation may occur.

The most severe of the facial defects (or anomalies) is cyclopia, an abnormality characterized by the development of a single eye, located in the area normally occupied by the root of the nose, and a missing nose or a nose in the form of a proboscis (a tubular appendage) located above the eye. The condition is also referred to as cyclocephaly or synophthalmia, and is very rare.

This syndrome is characterised by typical facial appearance, slight build, thin and translucent skin, severely adducted thumbs, arachnodactyly, club feet, joint instability, facial clefting and bleeding disorders, as well as heart, kidney or intestinal defects. Severe psychomotor and developmental delay and decreased muscle tone may also be present during infancy. Cognitive development during childhood is normal.

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).

The most common symptoms of Nicolaides–Baraitser syndrome are mild to severe developmental delays with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, and prominent finger joints and broad distal phalanges.

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

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.

Overactive disorder associated with mental retardation and stereotyped movements is a pervasive developmental disorder (PDD) listed in Chapter V(F) of the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10); its diagnostic code is F84.4.

HPE is not a condition in which the brain deteriorates over time. Although serious seizure disorders, autonomic dysfunction, complicated endocrine disorders and other life-threatening conditions may sometimes be associated with HPE, the mere presence of HPE does not mean that these serious problems will occur or develop over time without any previous indication or warning. These abnormalities are usually recognized shortly after birth or early in life and only occur if areas of the brain controlling those functions are fused, malformed or absent.

Prognosis is dependent upon the degree of fusion and malformation of the brain, as well as other health complications that may be present.

The more severe forms of encephalopathy are usually fatal. This disorder consists of a spectrum of defects, malformations and associated abnormalities. Disability is based upon the degree in which the brain is affected. Moderate to severe defects may cause mental retardation, spastic quadriparesis, athetoid movements, endocrine disorders, epilepsy and other serious conditions; mild brain defects may only cause learning or behavior problems with few motor impairments.

Seizures may develop over time with the highest risk before 2 years of age and the onset of puberty. Most are managed with one medication or a combination of medications. Typically, seizures that are difficult to control appear soon after birth, requiring more aggressive medication combinations/doses.

Most children with HPE are at risk of having elevated blood sodium levels during moderate-severe illnesses, that alter fluid intake/output, even if they have no previous diagnosis of diabetes insipidus or hypernatremia.

Infantile convulsions and choreoathetosis (ICCA) syndrome is a neurological genetic disorder with an autosomal dominant mode of inheritance. It is characterized by the association of benign familial infantile epilepsy (BIFE) at age 3–12 months and later in life with paroxysmal kinesigenic choreoathetosis. The ICCA syndrome was first reported in 1997 in four French families from north-western France and provided the first genetic evidence for common mechanisms shared by benign infantile seizures and paroxysmal dyskinesia. The epileptic origin of PKC has long been a matter of debates and PD have been classified as reflex epilepsies.Indeed, attacks of PKC and epileptic seizures have several characteristics in common, they both are paroxysmal in presentation with a tendency to spontaneous remission, and a subset of PKC responds well to anticonvulsants. This genetic disease has been mapped to chromosome 16p-q12. More than 30 families with the clinical characteristics of ICCA syndrome have been described worldwide so far.

This syndrome is associated with microcephaly, arthrogryposis and cleft palate and various craniofacial, respiratory, neurological and limb abnormalities, including bone and joint defects of the upper limbs, adducted thumbs, camptodactyly and talipes equinovarus or calcaneovalgus. It is characterized by craniosynostosis, and myopathy in association with congenital generalized hypertrichosis.

Patients with the disease are considered intellectually disabled. Most die in childhood. Patients often suffer from respiratory difficulties such as pneumonia, and from seizures due to dysmyelination in the brain's white matter. It has been hypothesized that the Moro reflex (startle reflex in infants) may be a tool in detecting the congenital clapsed thumb early in infancy. The thumb normally extends as a result of this reflex.

Affected children display severe psychomotor retardation, failure to thrive, seizures, and muscle spasticity or hypotonia. Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, fingers, or toes.

Spastic hemiplegia is a neuromuscular condition of spasticity that results in the muscles on one side of the body being in a constant state of contraction. It is the "one-sided version" of spastic diplegia. It falls under the mobility impairment umbrella of cerebral palsy. About 20–30% of people with cerebral palsy have spastic hemiplegia. Due to brain or nerve damage, the brain is constantly sending action potentials to the neuromuscular junctions on the affected side of the body. Similar to strokes, damage on the left side of the brain affects the right side of the body and damage on the right side of the brain affects the left side of the body.

The affected side of the body is rigid, weak and has low functional abilities. In most cases, the upper extremity is much more affected than the lower extremity. This could be due to preference of hand usage during early development. If both arms are affected, the condition is referred to as double hemiplegia. Some patients with spastic hemiplegia only suffer minor impairments, where in severe cases one side of the body could be completely paralyzed. The severity of spastic hemiplegia is dependent upon the degree of the brain or nerve damage.

Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive spasticity in the lower limbs due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia.

Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices.

More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles.

In the complex form of the disorder, additional symptoms are present. These include: peripheral neuropathy, amyotrophy, ataxia, mental retardation, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.

Anita Harding classified the HSP in a pure and complicated form. Pure HSP presents with spasticity in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity (pallhypesthesia). On the other hand, HSP is classified as complex when lower limb spasticity is combined with any additional neurological symptom.

This classification is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia with spasticity, mental retardation (with spasticity), or leukodystrophy. Some of the genes listed below have been described in other diseases than HSP before. Therefore, some key genes overlap with other disease groups.

Different imaging modalities are commonly used for diagnosis. While computed tomography (CT) provides higher spatial resolution imaging of the brain, cerebral cortex malformations are more easily visualized "in vivo" and classified using magnetic resonance imaging (MRI) which provides higher contrast imaging and better delineation of white and gray matter.

Diffuse pachygyria (a mild form of lissencephaly) can be seen on an MRI as thickened cerebral cortices with few and large gyri and incomplete development of the Sylvian fissures.

- severe epilepsy

- reduced longevity

- varying degrees of mental retardation

- intractable epilepsy

- spasticity

Cognitive ability correlates with the thickness of any subcortical band present and the degree of pachygyria.

Schizencephaly can be distinguished from porencephaly by the fact that in schizencephaly the fluid-filled component, if present, is entirely lined by heterotopic grey matter while a porencephalic cyst is lined mostly by white matter. Individuals with clefts in both hemispheres, or bilateral clefts, are often developmentally delayed and have delayed speech and language skills and corticospinal dysfunction. Individuals with smaller, unilateral clefts (clefts in one hemisphere) may be weak or paralyzed on one side of the body and may have average or near-average intelligence. Patients with schizencephaly may also have varying degrees of microcephaly, Intellectual disability, hemiparesis (weakness or paralysis affecting one side of the body), or quadriparesis (weakness or paralysis affecting all four extremities), and may have reduced muscle tone (hypotonia). Most patients have seizures, and some may have hydrocephalus.

Ohtahara syndrome is rare and the earliest-appearing age-related epileptic encephalopathy, with seizure onset occurring within the first three months of life, and often in the first ten days. Many, but not all, cases of OS evolve into other seizure disorders, namely West syndrome and Lennox-Gastaut syndrome.

The primary outward manifestation of OS is seizures, usually presenting as tonic seizures (a generalized seizure involving a sudden stiffening of the limbs). Other seizure types that may occur include partial seizures, clusters of infantile spasms, and, rarely, myoclonic seizures. In addition to seizures, children with OS exhibit profound mental and physical retardation.

Clinically, OS is characterized by a "burst suppression" pattern on an EEG. This pattern involves high voltage spike wave discharge followed by little brain wave activity.

It is named for the Japanese neurologist Shunsuke Ohtahara (1930–2013), who identified it in 1976.