The test is particularly indicated in children who have had cluster seizures in series. It is also recommended for patients who are diagnosed GEFS+ and when the seizures are associated with fever, infection, experienced regression, delayed cognitive growth or behavioral problems. The test is typically ordered by neurologists. The diagnostic test can be done by drawing blood or saliva of the patient and their immediate family. It is analyzed in laboratories that specialize in genetic testing. Genetic testing can aid in a firmer diagnosis and understanding of the disorder, may aid in identifying the optimal treatment plan and if positive, testing of the parents can determine if they are carriers. (See Genetic Counseling)

PCDH19 gene-related epilepsy is clinically based on patient and family seizure history, cognitive and behavioral neuropsychological evaluation, neurological examination, electroencephalogram (EEG) studies, and long term observation. Diagnosis is confirmed using molecular testing for PCDH19 mutations.

A patient’s DNA is sequenced from a blood sample with the use of the ABI Big Dye Terminator v.3.0 kit. Since this is a genetic disease, the basis of diagnosis lies in identifying genetic mutations or chromosomal abnormalities. The DNA sequence can be run with CLN8 Sanger Sequencing or CLN8 Targeted Familial Mutations whether its single, double, or triple Exon Sequencing. Also, preliminary evidence of the disease can be detected by means of MRI and EEG. These tests identify lipid content of the brain and any anomaly from the norm may be linked to Northern epilepsy.

The ring 20 abnormality may be limited to as few as 5% of cells, so a screen for chromosomal mosaicism is critical. Newer array technology will not detect the ring chromosome and the standard metaphase chromosome analysis has been recommended. A karyotype analysis examining at least 50 cells should be requested to properly detect mosaicism.

Two international research studies are currently underway. The International Genetic Study done with the Spinner Laboratory at The Children's Hospital of Philadelphia studies the ring 20 chromosome at the molecular level. The Clinical Research Study collects clinical information from parents to create a database of about the full spectrum of patients with ring chromosome 20 syndrome.

Epilepsy with myoclonic-astatic seizures has a variable course and outcome. Spontaneous remission with normal development has been observed in a few untreated cases. Complete seizure control can be achieved in about half of the cases with antiepileptic drug treatment (Doose and Baier 1987b; Dulac et al. 1990). In the remainder of cases, the level of intelligence deteriorates and the children become severely intellectually disabled. Other neurologic abnormalities such as ataxia, poor motor function, dysarthria, and poor language development may emerge (Doose 1992b). However, this proportion may not be representative because in this series the data were collected in an institution for children with severe epilepsy.

The outcome is unfavorable if generalized tonic-clonic, tonic, or clonic seizures appear at the onset or occur frequently during the course. Generalized tonic-clonic seizures usually occur during the daytime in this disorder, at least in the early stages. Nocturnal generalized tonic-clonic seizures, which may develop later, are another unfavorable sign. If tonic seizures appear, prognosis is poor.

Status epilepticus with myoclonic, astatic, myoclonic-astatic, or absence seizures is another ominous sign, especially when prolonged or appearing early.

Failure to suppress the EEG abnormalities (4- to 7-Hz rhythms and spike-wave discharges) during therapy and absence of occipital alpha-rhythm with therapy also suggest a poor prognosis (Doose 1992a).

Diagnosis of megalencephaly has changed over the years, however, with the development of more advanced equipment, physicians have been able to confirm the disorder with better accuracy. Usually, a physical exam is first performed when characteristics of megalencephaly have appeared. This typically occurs at birth or during early child development. A physician will then take head measurements in order to determine the circumference. This is known as the head circumference. Then a family background will be recorded in order to determine if there has been a history of megalencephaly in the family.

A neurological exam will then be performed using the technology of an MRI machine in order to confirm the diagnosis of megalencephaly. These imaging tests give detailed information regarding brain size, volume asymmetry and other irregular developments linked with MCAP, MPPH and hemimegalencephaly.

There is also a strong correlation of epilepsy and megalencephaly and this can aid doctors in their diagnosis.

If a diagnosis of megalencephaly is confirmed, the child is referred to a specialist who focuses on managing the symptoms and improving lifestyle. Since megalencephaly is usually presented with autism, the goal of treatment is to improve deficiencies associated with autistic causes. Additionally, since each patient has unique symptoms, there is no one specific treatment method and therefore is heavily reliant on symptoms associated with an individual.

Any number of medications may be used to both prevent and treat seizures.

Generally after three medications are tried, different treatment should be considered. It should also be noted that some medications are harmful to those with this syndrome and can increase seizures.

Life expectancy is only moderately affected by NE because the rate of disease progression is slow. Patients usually survive past 40-50 years of age.

No single cause of OS has been identified. In most cases, there is severe atrophy of both hemispheres of the brain. Less often, the root of the disorder is an underlying metabolic syndrome. Although it was initially published that no genetic connection had been established, several genes have since associated with Ohtahara syndrome. It can be associated with mutations in "ARX", "CDKL5", "SLC25A22", "STXBP1", "SPTAN1", "KCNQ2", "ARHGEF9", "PCDH19", "PNKP", "SCN2A", "PLCB1", "SCN8A", and likely others.

Treatment outlook is poor. Anticonvulsant drugs and glucocorticoid steroids may be used to try to control the seizures, but their effectiveness is limited. Most therapies are related to symptoms and day-to-day living.

Cases of epilepsy may be organized into epilepsy syndromes by the specific features that are present. These features include the age at which seizures begin, the seizure types, and EEG findings, among others. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as what anti-seizure medication should be tried.

The ability to categorize a case of epilepsy into a specific syndrome occurs more often with children since the onset of seizures is commonly early. Less serious examples are benign rolandic epilepsy (2.8 per 100,000), childhood absence epilepsy (0.8 per 100,000) and juvenile myoclonic epilepsy (0.7 per 100,000). Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as epileptic encephalopathies. These are associated with frequent seizures that are resistant to treatment and severe cognitive dysfunction, for instance Lennox-Gastaut syndrome and West syndrome.

Epilepsies with onset in childhood are a complex group of diseases with a variety of causes and characteristics. Some people have no obvious underlying neurological problems or metabolic disturbances. They may be associated with variable degrees of intellectual disability, elements of autism, other mental disorders, and motor difficulties. Others have underlying inherited metabolic diseases, chromosomal abnormalities, specific eye, skin and nervous system features, or malformations of cortical development. Some of these epilepsies can be categorized into the traditional epilepsy syndromes. Furthermore, a variety of clinical syndromes exist of which the main feature is not epilepsy but which are associated with a higher risk of epilepsy. For instance between 1 and 10% of those with Down syndrome and 90% of those with Angelman syndrome have epilepsy.

In general, genetics is believed to play an important role in epilepsies by a number of mechanisms. Simple and complex modes of inheritance have been identified for some of them. However, extensive screening has failed to identify many single rare gene variants of large effect. In the epileptic encephalopathies, de novo mutagenesis appear to be an important mechanism. De novo means that a child is affected, but the parents do not have the mutation. De novo mutations occur in eggs and sperms or at a very early stage of embryonic development. In Dravet syndrome a single affected gene was identified.

Syndromes in which causes are not clearly identified are difficult to match with categories of the current classification of epilepsy. Categorization for these cases is made somewhat arbitrarily. The "idiopathic" (unknown cause) category of the 2011 classification includes syndromes in which the general clinical features and/or age specificity strongly point to a presumed genetic cause. Some childhood epilepsy syndromes are included in the unknown cause category in which the cause is presumed genetic, for instance benign rolandic epilepsy. Others are included in "symptomatic" despite a presumed genetic cause (in at least in some cases), for instance Lennox-Gastaut syndrome. Clinical syndromes in which epilepsy is not the main feature (e.g. Angelman syndrome) were categorized "symptomatic" but it was argued to include these within the category "idiopathic". Classification of epilepsies and particularly of epilepsy syndromes will change with advances in research.

West syndrome is a triad of developmental delay, seizures termed infantile spasms, and EEG demonstrating a pattern termed hypsarrhythmia. Onset occurs between three months and two years, with peak onset between eight and 9 months. West syndrome may arise from idiopathic, symptomatic, or cryptogenic causes. The most common cause is tuberous sclerosis. The prognosis varies with the underlying cause. In general, most surviving patients remain with significant cognitive impairment and continuing seizures and may evolve to another eponymic syndrome, Lennox-Gastaut syndrome. It can be classified as idiopathic, syndromic, or cryptogenic depending on cause and can arise from both focal or generalized epileptic lesions.

As of 1993 only approximately 30 people with AHC had been described in scientific literature. Due to the rarity and complexity of AHC, it is not unusual for the initial diagnosis to be incorrect, or for diagnosis to be delayed for several months after the initial symptoms become apparent. The average age of diagnosis is just over 36 months. Diagnosis of AHC is not only difficult because of its rarity, but because there is no diagnostic test, making this a diagnosis of exclusion. There are several generally accepted criteria which define this disorder, however other conditions with a similar presentation, such as HSV encephalitis, must first be ruled out. Due to these diagnostic difficulties, it is possible that the commonness of the disease is underestimated.

The following descriptions are commonly used in the diagnosis of AHC. The initial four criteria for classifying AHC were that it begins before 18 months of age, includes attacks of both hemiplegia on either side of the body, as well as other autonomic problems such as involuntary eye movement (episodic monocular nystagmus), improper eye alignment, choreoathetosis, and sustained muscle contractions (dystonia). Finally, patients suffer from intellectual disabilities, delayed development, and other neurological abnormalities. These diagnostic criteria were updated in 1993 to include the fact that all of these symptoms dissipate immediately upon sleeping. Diagnostic criteria were also expanded to include episodes of bilateral hemiplegia which shifted from one side of the body to the other.

Recent criteria have been proposed for screening for AHC early, in order to improve the diagnostic timeline. These screening criteria include focal or unilateral paroxysmal dystonia in the first 6 months of life, as well as the possibility of flaccid hemiplegia either with or separate from these symptoms. Paroxysmal ocular movements should also be considered, and these should include both binocular and monocular symptoms which show in the first 3 months of life.

Since there are very few treatment methods focused on managing megalencephaly, future research is targeted at inhibiting mutation of the pathway. However, this next step could be met with several complications as understanding the underlying mechanism of the mutation is a difficult task. The genetic coding that initiates a single mutation is sporadic and patterns are hard to detect in many cases.

Even thought very little research has been done to create inhibitors of the PI3K-AKT pathway, several pharmaceutical companies have begun to focus their interests in designing a prevention method for this purpose.

Over the past decade or so, researchers have been attempting to discover less invasive, safer and more efficient technologies that enable surgeons to remove epileptogenic focal zones without causing any damage to neighboring cortical areas. One such technology that has emerged and has great promise, is the use of gamma knife radiosurgery to either excise a brain tumor or repair a vascular malformation.

In Gamma Knife radiosurgery, intersecting gamma radiation beams are applied directly to the tumor site or vascular malformation site that had been established using neuroimaging. Although each beam itself is not strong enough to damage brain tissue, when the beams interesect they are strong enough to destroy the specific brain tissue that is to be excised. This process is extremely efficient and entirely non-invasive and is therefore much safer than actual neurosurgery itself.

Recently researchers and surgeons alike have begun to use Gamma Knife radiosurgery to treat cases of epilepsy by removing tumors responsible for causing the seizures. The early success rates in being able to alleviate seizures seem to be similar to those of temporal resective surgery however Gamma Knife radiosurgery has less associated risk factors. Current research on this topic is aimed at improving the technique in order to increase success rates as well as developing non-invasive forms of physiologic monitoring in order to determine the epileptogenic focus conclusively.

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.

There are several different ways to treat frontal lobe epileptic seizures, however, the most common form of treatment is through the use of anticonvulsant medications that help to prevent seizures from occurring. In some cases, however, when medications are ineffective, a neurologist may choose to operate on the patient in order to remove the focal area of the brain in which the seizures are occurring. Other treatments that can be administered to aid in reducing the occurrence of seizures include the implementation of a specific, regimented diet and/or the implantation of a vagus nerve stimulator.

Myoclonus can be described as brief jerks of the body; it can involve any part of the body, but it is mostly seen in limbs or facial muscles. The jerks are usually involuntary and can lead to falls. EEG is used to read brain wave activity. Spike activity produced from the brain is usually correlated with brief jerks seen on EMG or excessive muscle artifact. They usually occur without detectable loss of consciousness and may be generalized, regional or focal on the EEG tracing. Myclonus jerks can be epileptic or not epileptic. Epileptic myoclonus is an elementary electroclinical manifestation of epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity.

Juvenile myoclonic epilepsy is responsible for 7% of cases of epilepsy. Seizures usually begin around puberty and usually have a genetic basis. Seizures can be stimulus-selective, with flashing lights being one of the most common triggers.

Long term management is by use of anticonvulsant medication, principally valproate, stiripentol, topiramate or clobazam. Ketogenic diet has also been found useful in certain cases

Management of breakthrough seizures is by benzodiazepine such as midazolam.

When seizures are present in any forms of cortical dysplasia, they are resistant to medication. Frontal lobe resection provides significant relief from seizures to a minority of patients with periventricular lesions.

Males with pathogenic "MECP2" mutations usually die within the first 2 years from severe encephalopathy, unless they have an extra X chromosome (often described as Klinefelter syndrome), or have somatic mosaicism.

Male fetuses with the disorder rarely survive to term. Because the disease-causing gene is located on the X chromosome, a female born with an MECP2 mutation on her X chromosome has another X chromosome with an ostensibly normal copy of the same gene, while a male with the mutation on his X chromosome has no other X chromosome, only a Y chromosome; thus, he has no normal gene. Without a normal gene to provide normal proteins in addition to the abnormal proteins caused by a MECP2 mutation, the XY karyotype male fetus is unable to slow the development of the disease, hence the failure of many male fetuses with a MECP2 mutation to survive to term.

Females with a MECP2 mutation, however, have a non-mutant chromosome that provides them enough normal protein to survive longer. Research shows that males with Rett syndrome may result from Klinefelter's syndrome, in which the male has an XXY karyotype. Thus, a non-mutant "MECP2" gene is necessary for a Rett's-affected embryo to survive in most cases, and the embryo, male or female, must have another X chromosome.

There have, however, been several cases of 46,XY karyotype males with a MECP2 mutation (associated with classical Rett syndrome in females) carried to term, who were affected by neonatal encephalopathy and died before 2 years of age. The incidence of Rett syndrome in males is unknown, partly owing to the low survival of male fetuses with the Rett syndrome-associated MECP2 mutations, and partly to differences between signs caused by MECP2 mutations and those caused by Rett's.

Females can live up to 40 years or more. Laboratory studies on Rett syndrome may show abnormalities such as:

- EEG abnormalities from 2 years of age

- atypical brain glycolipids

- elevated CSF levels of "beta"-endorphin and glutamate

- reduction of substance P

- decreased levels of CSF nerve growth factors

A high proportion of deaths are abrupt, but most have no identifiable cause; in some instances death is the result most likely of:

- spontaneous brainstem dysfunction

- cardiac arrest, likely due to long QT syndrome, ventricular tachycardia or other arrhythmias

- seizures

- gastric perforation

Overall outcomes for AHC are generally poor, which is contributed to by AHC's various diagnostic and management challenges. In the long term, AHC is debilitating due to both the hemiplegic attacks and permanent damage associated with AHC. This damage can include cognitive impairment, behavioral and psychiatric disorders, and various motor impairments. There is, however, not yet any conclusive evidence that AHC is fatal or that it shortens life expectancy, but the relatively recent discovery of the disorder makes large data for this type of information unavailable. Treatment for AHC has not been extremely successful, and there is no cure. There are several drugs available for treatment, as well as management strategies for preventing and dealing with hemiplegic attacks.

Prior to the discovery of a genetic cause, Rett syndrome had been designated as a pervasive developmental disorder by the "Diagnostic and Statistical Manual of Mental Disorders" (DSM), together with the autism spectrum disorders. Some argued against this conclusive assignment because RTT resembles non-autistic disorders such as fragile X syndrome, tuberous sclerosis, or Down syndrome that also exhibit autistic features.

After research proved the molecular mechanism, in 2013 the DSM-5 removed the syndrome altogether from classification as a mental disorder.

Rett syndrome diagnosis involves close observation of the child's growth and development to observe any abnormalities in regards to developmental milestones. A diagnosis is considered when decreased head growth is observed. Conditions with similar symptoms must first be ruled out.

There is a certain criteria that must be met for the diagnosis. A blood test can rule in or rule out the presence of the MECP2 mutation, however, this mutation is present in other conditions as well.

For a classic diagnosis, all four criteria for ruling in a diagnosis must be met, as well as the two criteria for ruling out a diagnosis. A period of symptom regression followed by recovery or symptom stabilization must also occur. Supportive criteria may also be present, but are not required for diagnosis. For an atypical or variant diagnosis, at least two of the four criteria for ruling in the diagnosis must be met, as well as five of the eleven supportive criteria. A period of symptom regression followed by recovery or symptom stabilization must also occur. Children are often misdiagnosed as having autism, cerebral palsy, or another form of developmental delay. A positive test for the MECP2 mutation is not enough to make a diagnosis.

Ruling in

- Decreased or loss of use of fine motor skills

- Decreased or loss of verbal speech

- Abnormalities during gait

- Repetitive hand movements such as wringing/squeezing or clapping/tapping

Ruling out

- Traumatic brain injury, neurometabolic disease, or severe infection that may better explain symptoms

- Abnormal psychomotor development during the 6 months of life

Supportive criteria

- Breathing disturbances when awake

- Bruxism while awake

- Impaired sleep pattern

- Abnormal muscle tone

- Peripheral vasomotor disturbances

- Scoliosis/kyphosis

- Growth retardation

- Small cold hands and feet

- Inappropriate laughing/screaming spells

- Diminished response to pain

- Intense eye communication (eye pointing)

Cytogenetic analysis for fragile X syndrome was first available in the late 1970s when diagnosis of the syndrome and carrier status could be determined by culturing cells in a folate deficient medium and then assessing for "fragile sites" (discontinuity of staining in the region of the trinucleotide repeat) on the long arm of the X chromosome. This technique proved unreliable, however, as the fragile site was often seen in less than 40% of an individual's cells. This was not as much of a problem in males, but in female carriers, where the fragile site could generally only be seen in 10% of cells, the mutation often could not be visualised.

Since the 1990s, more sensitive molecular techniques have been used to determine carrier status. The fragile X abnormality is now directly determined by analysis of the number of CGG repeats using polymerase chain reaction (PCR) and methylation status using Southern blot analysis. By determining the number of CGG repeats on the X chromosome, this method allows for more accurate assessment of risk for premutation carriers in terms of their own risk of fragile X associated syndromes, as well as their risk of having affected children. Because this method only tests for expansion of the CGG repeat, individuals with FXS due to missense mutations or deletions involving "FMR1" will not be diagnosed using this test and should therefore undergo sequencing of the FMR1 gene if there is clinical suspicion of FXS.

Prenatal testing with chorionic villus sampling or amniocentesis allows diagnosis of FMR1 mutation while the fetus is in utero and appears to be reliable.

Early diagnosis of fragile X syndrome or carrier status is important for providing early intervention in children or fetuses with the syndrome, and allowing genetic counselling with regards to the potential for a couple's future children to be affected. Most parents notice delays in speech and language skills, difficulties in social and emotional domains as well as sensitivity levels in certain situations with their children.