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.

Diagnosis is made upon history of absence seizures during early childhood and the observation of ~3 Hz spike-and-wave discharges on an EEG.

The only currently available method to diagnose Unverricht–Lundborg disease is a genetic test to check for the presence of the mutated cystatin B gene. If this gene is present in an individual suspected of having the disease, it can be confirmed. However, genetic tests of this type are prohibitively expensive to perform, especially due to the rarity of ULD. The early symptoms of ULD are general and in many cases similar to other more common epilepsies, such as juvenile myoclonic epilepsy. For these reasons, ULD is generally one of the last options doctors explore when looking to diagnose patients exhibiting its symptoms. In most cases, a misdiagnosis is not detrimental to the patient, because many of the same medications are used to treat both ULD and whatever type of epilepsy the patient has been misdiagnosed with. However, there are a few epilepsy medications that increase the incidence of seizures and myoclonic jerks in patients with ULD, which can lead to an increase in the speed of progression, including phenytoin, fosphenytoin, sodium channel blockers, GABAergic drugs, gabapentin and pregabalin.

Other methods to diagnose Unverricht–Lundborg disease are currently being explored. While electroencephalogram (EEG) is useful in identifying or diagnosing other forms of epilepsy, the location of seizures in ULD is currently known to be generalized across the entire brain. Without a specific region to pinpoint, it is difficult to accurately distinguish an EEG reading from an individual with ULD from an individual with another type of epilepsy characterized by generalized brain seizures. However, with recent research linking ULD brain damage to the hippocampus, the usefulness of EEG as a diagnostic tool may increase.

Magnetic Resonance Imaging (MRI) is also often used during diagnosis of patients with epilepsy. While MRIs taken during the onset of the disease are generally similar to those of individuals without ULD, MRIs taken once the disease has progressed show characteristic damage, which may help to correct a misdiagnosis.

While ULD is a rare disease, the lack of well defined cases to study and the difficulty in confirming diagnosis provide strong evidence that this disease is likely under diagnosed.

Unverricht–Lundborg disease is also known as EPM1, as it is a form of progressive myoclonic epilepsy (PME). Other progressive myoclonic epilepsies include myoclonus epilepsy and ragged red fibers (MERRF syndrome), Lafora disease (EPM2a or EMP2b), Neuronal ceroid lipofuscinosis (NCL) and sialidosis. Progressive myoclonic epilepsies generally constitute only a small percentage of epilepsy cases seen, and ULD is the most common form. While ULD can lead to an early death, it is considered to be the least severe form of progressive myoclonic epilepsy.

Childhood absence epilepsy is a fairly common disorder with a prevalence of 1 in 1000 people. Few of these people will likely have mutations in CACNA1H or GABRG2 as the prevalence of those in the studies presented is 10% or less.

PME accounts for less than 1% of epilepsy cases at specialist centres. The incidence and prevalence of PME is unknown, but there are considerable geography and ethnic variations amongst the specific genetic disorders. One cause, Unverricht Lundborg Disease, has an incidence of at least 1:20,000 in Finland.

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.

Neonatal seizures are often controlled with phenobarbital administration. Recurrent seizures later in life are treated in the standard ways (covered in the main epilepsy article). Depending on the severity, some infants are sent home with heart and oxygen monitors that are hooked to the child with stick on electrodes to signal any seizure activity. Once a month the monitor readings are downloaded into a central location for the doctor to be able to read at a future date. This monitor is only kept as a safeguard as usually the medication wards off any seizures. Once the child is weaned off the phenobarbital, the monitor is no longer necessary.

This is an autosomal recessive disorder in which the body is deficient in α-neuraminidase.

Several disorders may appear similar to CBPS and need to be distinguished in the process of diagnosing CBPS. These include pachygyria, double cortex syndrome, and lissencephaly, all of which are classified along with CBPS as neuronal migration disorders. Diagnostic tests for CBPS include electroencephalograms, CT scanning, and magnetic resonance imaging.

CBPS is commonly treated with anticonvulsant therapy to reduce seizures. Therapies include anticonvulsant drugs, adrenocorticotropic hormone therapy, and surgical therapy, including focal corticectomy and callosotomy. Special education, speech therapy, and physical therapy are also used to help children with intellectual disability due to CBPS.

Depending on subtype, many patients find that acetazolamide therapy is useful in preventing attacks. In some cases, persistent attacks result in tendon shortening, for which surgery is required.

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.

Protein function tests that demonstrate a reduce in chorein levels and also genetic analysis can confirm the diagnosis given to a patient. For a disease like this it is often necessary to sample the blood of the patient on multiple occasions with a specific request given to the haematologist to examine the film for acanthocytes. Another point is that the diagnosis of the disease can be confirmed by the absence of chorein in the western blot of the erythrocyte membranes.

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.

Diagnosis is achieved by examining the structure of the chromosomes through karyotyping; while once born, one can do the following to ascertain a diagnosis of the condition:

- MRI

- EEG

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.

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.

Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognised but the majority are due to two recognized entities. Ataxia can be provoked by stress, startle, or heavy exertion such as exercise. Symptoms can first appear in infancy. There are at least 6 loci for EA, of which 4 are known genes. Some patients with EA also have migraine or progressive cerebellar degenerative disorders, symptomatic of either familial hemiplegic migraine or spinocerebellar ataxia. Some patients respond to acetazolamide though others do not.

Blood tests usually come back normal in affected individuals, so they do not serve as a reliable means of diagnosis. Blood tests can show low serum ferritin levels. However, this is unreliable as method of diagnosis, as some patients show typical serum ferritin levels even at the latest stages of neuroferritinopathy. Cerebral spinal fluid tests also are typically normal.

Ferritin found in the skin, liver, kidney, and muscle tissues may help in diagnosing neuroferritinopathy. More cytochrome c oxidase-negative fibers are also often found in the muscle biopsies of affected individuals.

Genetic testing can confirm a neuroferritinopathy diagnosis. A diagnosis can be made by analyzing the protein sequences of affected individuals and comparing them to known neuroferritinopathy sequences.

Diagnosis is clinical and initially consists of ruling out more common conditions, disorders, and diseases, and usually begins at the general practitioner level. A doctor may conduct a basic neurological exam, including coordination, strength, reflexes, sensation, etc. A doctor may also run a series of tests that include blood work and MRIs.

From there, a patient is likely to be referred to a neurologist or a neuromuscular specialist. The neurologist or specialist may run a series of more specialized tests, including needle electromyography EMG/ and nerve conduction studies (NCS) (these are the most important tests), chest CT (to rule out paraneoplastic) and specific blood work looking for voltage-gated potassium channel antibodies, acetylcholine receptor antibody, and serum immunofixation, TSH, ANA ESR, EEG etc. Neuromyotonia is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high, irregular intraburst frequency. Fibrillation potentials and fasciculations are often also present with electromyography.

Because the condition is so rare, it can often be years before a correct diagnosis is made.

NMT is not fatal and many of the symptoms can be controlled. However, because NMT mimics some symptoms of motor neuron disease (ALS) and other more severe diseases, which may be fatal, there can often be significant anxiety until a diagnosis is made. In some rare cases, acquired neuromyotonia has been misdiagnosed as amyotrophic lateral sclerosis (ALS) particularly if fasciculations may be evident in the absence of other clinical features of ALS. However, fasciculations are rarely the first sign of ALS as the hallmark sign is weakness. Similarly, multiple sclerosis has been the initial misdiagnosis in some NMT patients. In order to get an accurate diagnosis see a trained neuromuscular specialist.

Pathologically, PMG is defined as “an abnormally thick cortex formed by the piling upon each other of many small gyri with a fused surface.” To view these microscopic characteristics, magnetic resonance imaging (MRI) is used. First physicians must distinguish between polymicrogyria and pachygyria. Pachygria leads to the development of broad and flat regions in the cortical area, whereas the effect of PMG is the formation of multiple small gyri. Underneath a computerized tomography (CT scan) scan, these both appear similar in that the cerebral cortex appears thickened. However, MRI with a T1 weighted inversion recovery will illustrate the gray-white junction that is characterized by patients with PMG. An MRI is also usually preferred over the CT scan because it has sub-millimeter resolution. The resolution displays the multiple folds within the cortical area, which is continuous with the neuropathology of an infected patient.

Benign familial neonatal seizures (BFNS), formerly called benign familial neonatal convulsions (BFNC), is a rare autosomal dominant inherited form of seizures. It manifests in newborns, normally within the first 7 days of life, as tonic-clonic seizures. Infants are otherwise normal between attacks and develop without incident. Attacks normally spontaneously cease within the first 15 weeks of life. Lifetime susceptibility to seizures is increased, as 16% of those diagnosed with BFNE earlier in life will go on to have seizures versus a 2% lifetime risk for the general population. There are three known genetic causes of BFNE, two being the voltage-gated potassium channels KCNQ2 (BFNC1) and KCNQ3 (BFNC2) and the third being a chromosomal inversion (BFNC3). There is no obvious correlation between most of the known mutations and clinical variability seen in BFNE.

Neuromyotonia is a type of peripheral nerve hyperexcitability. Peripheral nerve hyperexcitability is an umbrella diagnosis that includes (in order of severity of symptoms from least severe to most severe) benign fasciculation syndrome, cramp fasciculation syndrome, and neuromyotonia. Some doctors will only give the diagnosis of peripheral nerve hyperexcitability as the differences between the three are largely a matter of the severity of the symptoms and can be subjective. However, some objective EMG criteria have been established to help distinguish between the three.

Moreover, the generic use of the term "peripheral nerve hyperexcitability syndromes" to describe the aforementioned conditions is recommended and endorsed by several prominent researchers and practitioners in the field.