Clinical manifestations of IGE depend on its subtype. The patient's history may point towards the diagnosis. Some of the syndromes of IGE overlap and therefore may be difficult to distinguish initially.

Benign myoclonic epilepsy in infancy manifests with mild jerks at the start, with their severity increasing progressively. Falls are quite uncommon in this subgroup. Head drops and deviation of the eyes in the upward direction are observed on a daily basis. Some of the patients present with myoclonus triggered by stimuli such as sudden noises or tapping. The degree of cognitive impairment is low, especially in children who respond well to treatment [10].

Generalized epilepsy with febrile seizures plus, an entity in evolution, represents a group of syndromes observed in several family members that have previously experienced febrile seizures. The condition presents with mild convulsions occasionally. Some patients present with seizures resembling the clinical presentation of myoclonic-astatic epilepsy or severe myoclonic epilepsy in infancy (Dravet syndrome). Genes involved in epilepsy may be uncovered by a proper analyses of families with generalized epilepsy with febrile seizures plus.

Epilepsy with myoclonic-astatic seizures (also known as Doose syndrome) is another form of IGE typically starting with a febrile seizure. Myoclonic-astatic seizures consist of symmetric myoclonic jerks followed by periods of absent muscle tone that can result in falls. In some patients, only head nodding may be observed. Absence or myoclonic absence seizures are most commonly observed in children.

Epilepsy with myoclonic absences is characterized by an alteration in consciousness accompanied by rhythmic myoclonic jerks and tonic contractions of the extremities, lasting for 8 to 60 seconds and occurring several times a day. The jerks may be symmetric or asymmetric while the tonic contractions occur primarily in the proximal regions of the arms [11].

Childhood absence epilepsy (or pyknolepsy) consist of changes in consciousness called absences. They may include memory, awareness or responsiveness problems as well as motor features such as automatisms, eye deviations, rhythmic muscle contractions or clonus of the eyelids. All these form a part of simple absence seizures. More massive motor manifestations constitute a part of complex absence seizures.

Juvenile myoclonic epilepsy is a form of IGE represented by myoclonic seizures. These typically occur in the morning with sudden dropping of objects and jerks located in the neck, shoulders, arms or legs. The extensors of the arm are the most frequently involved muscle groups. Falls as well as changes in consciousness are rare, although short absence seizures without automatisms are reported in 30% of the patients [12].

Epilepsy with generalized tonic–clonic seizures is a syndrome with wide range of clinical presentations. Seizures can appear at any time and are aggravated by sleep deprivation and alcohol abuse, similar to almost all other types of epilepsy.

• Falling

  Myoclonic-astatic seizures consist of symmetric myoclonic jerks followed by periods of absent muscle tone that can result in falls. In some patients, only head nodding may be observed. [symptoma.com]

  A person will lose consciousness and fall to the ground. Their muscles will contract and jerk rhythmically. Seizures generally last for a short duration less than two minutes. [study.com]

  Falling. If you fall during a seizure, you can injure your head or break a bone. Drowning. [mayoclinic.org]

  Children with this disorder have incredibly brief (<100ms) myoclonic jerks followed by equally brief loss of muscle tone, sometimes resulting in dangerous falls. Some patients have much longer lasting seizures of this type. [en.wikipedia.org]

  “When the spirit seizes him, the patient suddenly cries out, falls to the ground, foaming, and grinding the teeth. Luke 9:39. [ncbi.nlm.nih.gov]

• Movement Disorder

  Disorders and Physiology Graduate School of Medicine, Kyoto, Japan. [ncbi.nlm.nih.gov]

• Visual Impairment

  Deep stromal involvement has also been reported and may result in visual impairment. Other Skin Manifestations Herpes simplex virus infections can manifest at any skin site. [ncbi.nlm.nih.gov]

• Muscle Twitch

  twitching, irritability and convulsions may occur) � Na rarely causes symptoms when Na > 125 mmol/l except when decrease in concentration has been rapid Treatment (euvolaemic hyponatraemia) � Charles Gomersall December 1999 [aic.cuhk.edu.hk]

• Osteoporosis

  Could this drug increase my risk for osteoporosis? One thing to keep in mind: Osteoporosis is a weakening of the bone structure that can occur as you get older. [webmd.com]

• Seizure

  Clinically, IGE is characterized by the occurrence of any of the following three seizure types: absence seizures, myoclonic seizures and primarily generalized tonic-clonic seizures. [ncbi.nlm.nih.gov]

• Generalized Tonic-Clonic Seizure

  […] or primarily generalized tonic-clonic seizures. [ncbi.nlm.nih.gov]

  juvenile absence epilepsy; juvenile myoclonic epilepsy; and epilepsy with generalized tonic–clonic seizures. [symptoma.com]

• Febrile Seizures

  Febrile seizures and a positive family history were common. Good seizure control was achieved after temporal lobectomy, even when interictal generalized activity predominated. [ncbi.nlm.nih.gov]

  Epilepsy with myoclonic-astatic seizures (also known as Doose syndrome) is another form of IGE typically starting with a febrile seizure. [symptoma.com]

  Generalized epilepsy with febrile seizures plus[edit] Generalized epilepsy with febrile seizures plus (GEFS+) is an umbrella for many other syndromes that share causative genes. [en.wikipedia.org]

  seizures plus, Early infantile epileptic encephalopathy 6, Generalized epilepsy with febrile seizures plus, type 2, Febrile seizures, familial 3A AD 718 1585 SCN1B Atrial fibrillation, Brugada syndrome, Generalized epilepsy with febrile seizures plus [blueprintgenetics.com]

• Confusion

  Some patients with idiopathic/genetic generalized epilepsy (IGE) experience visual aura, which can confuse the diagnosis. We sought to determine the frequency and characteristics of visual auras in IGE patients. [ncbi.nlm.nih.gov]

  If you're confused or don't know what's happening during your seizure -- or don't remember it -- it's an impaired awareness seizure. These used to be called "complex partial seizures." Focal motor seizures. [webmd.com]

  […] for anyone who develops severe signs and symptoms of hyponatremia, such as nausea and vomiting, confusion, seizures, or lost consciousness. [mayoclinic.org]

• Myoclonus

  She had a dramatic response to piracetam with sustained cessation of myoclonus and no side effects during 1.5 years' follow-up. Further trials of piracetam for control of myoclonus in patients with IGE are justified. [ncbi.nlm.nih.gov]

  In absence epilepsies, development of myoclonus and generalized tonic-clonic seizures predicts lower likelihood of remission. [research.monash.edu]

Electroencephalogram (EEG) is the laboratory test of choice for the diagnosis of IGE. However, EEG does not always allow distinction between the different syndromes, especially the overlapping ones. EEG changes are usually non-specific, with specific changes attributed to the different subtypes occurring in some cases. EEG usually shows bilateral, synchronous generalized spike-and-wave (GSW) or polyspike-and-wave discharges with a normal background. Asymmetries or pseudofocalities may also be observed in some patients [13] [14] [15] [16].

Interictal EEG in benign myoclonic epilepsy in infancy is usually normal. Fast generalized spike or polyspike-wave discharges may be observed during the myoclonic episodes. The use of video-EEG is recommended for their recording [17].

In order to differentiate IGE from focal epilepsy with rapid secondary generalization, physical examination, EEG studies (interictal EEG, video EEG) or radiographic tests should be performed.

• Generalized Epileptiform Discharges

  Circadian variations of generalized epileptiform discharges are well described, and these can be useful in diagnostic confirmation. [ncbi.nlm.nih.gov]

  They comprise 15–20% of all epilepsies.1,2 GGEs are characterized by different combinations of generalized seizures such as absence, myoclonic, and generalized tonic–clonic and generalized epileptiform discharges on electroencephalography (EEG). [dovepress.com]

  The co-occurrence of focal and generalized epileptiform discharges, as well as focal and generalized seizure types within one syndrome were not novel. [nature.com]

• 3-4 Hz Spikes

  […] epilepsy 9–13 years Sex: ♂ = ♀ Absence seizures Tonic-clonic seizures (on awakening) are common Photosensitivity less common Regular 3–4 Hz spikes and waves in all regions of the brain 1st-line: valproic acid Avoid triggers: sleep deprivation, alcohol [amboss.com]

  Her EEG showed 3–4 Hz spike and wave discharges. She had a daughter with childhood absence epilepsy, and two sisters and a cousin with seizures (fig 2⇓, family 1). [jnnp.bmj.com]

• Focal Spikes

  Generalized spike-and-wave often becomes fragmented with sleep deprivation or in sleep. Fragmented generalized spike-and-wave can appear focal or multi-focal but usually is not consistently seen in 1 area. [medlink.com]

  The interictal EEG showed generalized spike-and-wave alone in 8 patients, focal or multifocal spike-and-wave alone in 3 patients, both generalized and focal spike-and-wave in 10 patients. No interictal discharges were observed in one patient. [nature.com]

• Spike-and-Slow-Waves

  waves Abnormal interictal EEG: slow spike-wave pattern Attempt anticonvulsive treatment, e.g., valproic acid, clobazam, lamotrigine, felbamate [13] Ketogenic diet, vagus nerve stimulation, surgery (see therapy of epilepsy) Poor; only 10% are seizure-free [amboss.com]

  An absence seizure was defined as a clinical change associated with generalized spike and slow wave or multiple spike and slow wave with a frequency of greater than 2.5 Hz at the onset. [jamanetwork.com]

  Panayiotopoulos et al. (1994) [21] observed that 51.5% of patients had spike/multiple spike-slow wave discharges. In a study by Jain et al. (2003), [7] EEG was abnormal in 90% of drug-naïve JME. [annalsofian.org]

• Multifocal Spikes

  Lennox-Gastaut syndrome 3–5 years Sex: ♂ > ♀ Majority of cases due to structural brain abnormalities 40% of cases are cryptogenic Multiple types of seizures: myoclonic, tonic, atonic, absences Developmental delays Frequently periods of status epilepticus Multifocal [amboss.com]

  The interictal EEG showed generalized spike-and-wave alone in 8 patients, focal or multifocal spike-and-wave alone in 3 patients, both generalized and focal spike-and-wave in 10 patients. No interictal discharges were observed in one patient. [nature.com]

Different groups of antiepileptic medications are indicated in the management of IGE.

Valproate is the drug of choice for all IGE syndromes as it is effective for all types of seizures. However, valproate is not well tolerated by all patients. Moreover, valproate is considered as a teratogen. Pregnant woman or those planning pregnancy should use levetiracetam instead of valproate.

Drugs such as carbamazepine, oxcarbazepine and pregabalin, frequently used in focal and partial seizures, may aggravate absence seizures and/or myoclonus. They should, thus, be avoided in IGE syndromes with similar manifestations.

First-line drugs for childhood absence epilepsy include ethosuximide, valproate, topiramate or lamotrigine. Levetiracetam and zonisamide can also be used.

Treatment of IGE should always include patient counseling in order to establish and control the triggering factors for such seizures.

Although studies on the prognosis of IGE are lacking compared to other epilepsy syndromes, IGE seems to have a better prognosis. However, lifelong treatment may be necessary, especially in JME patients. With the aid of anti-epileptic drugs, JME patients usually achieve remission easily; however, on stopping the anti-epileptic medications, less than 20% of them remain in remission, thus highlighting the need for life-long treatment. A higher rate of remission has been observed in childhood absence epilepsy. Appearance of myoclonus or generalized tonic-clonic seizures is a poor indicator for remission. The social outcome in IGE patients may be unsatisfactory even with good seizure control. Using EEG as an indicator of prognosis is not entirely supported by studies. Research into accurately defining the prognostic criteria is ongoing.

Although the mode of inheritance remains uncertain, at least two or more genes are likely to be involved in IGE inheritance. However, the exact genes have not been found yet. In different studies, mutations in α1 and γ2 GABA-A-receptor subunit as well as in CLC-2 voltage-gated chloride channel (CLCN2) gene have been identified [1] [2] [3].

It has been suggested that the mother has a greater role in the inheritance of IGE [4] [5].

IGE represents 15-20% of all epileptic conditions.

IGE usually manifests between early childhood and adolescence with different ages of onset depending on the type of IGE. IGE affects otherwise healthy individuals. No major difference in sex and racial distributions of the condition are observed.

Juvenile absence epilepsy (JAE) and juvenile myoclonic epilepsy usually appear between the age of 10 and 18 years. There is however, a childhood form of JAE affecting children between 6 and 8 years.

Benign myoclonic epilepsy as well as epilepsy with myoclonic-astatic seizures typically begin at 5 months to 5 years, while epilepsy with generalized tonic-clonic seizures has an onset between 6 and 28 years, peaking at 17 years.

As mentioned, IGE includes several subtypes- benign myoclonic epilepsy in infancy; generalized epilepsy with febrile seizures plus, an entity in evolution; epilepsy with myoclonic absences; epilepsy with myoclonic-astatic seizures; childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and epilepsy with generalized tonic–clonic seizures. It is still unclear if they all have similar mutations and pathophysiologic mechanisms [6] [7] [8] [9].

In terms of prevention, several measures can be undertaken in order to minimize the risk of epilepsy. These include reducing the risk factors for brain injury, heart attack and stroke, maintaining an up-to-date vaccination calendar as well as following all recommendations in pregnancy.

According to the International League Against Epilepsy (ILAE), the category of idiopathic generalized epilepsy (IGE) includes eight different syndromes: benign myoclonic epilepsy in infancy, epilepsy with myoclonic absences, epilepsy with myoclonic-astatic seizures, epilepsy with generalized tonic–clonic seizure, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy open link, and generalized epilepsy with febrile seizures plus, an entity in evolution.

All of them are genetic disorders although the exact etiology remains unclear. IGE is equally present in males and females. No wide differences in disease prevalence have been observed amongst different races. The disease usually persists for life.

The different subtypes of IGE are differentiated mainly on the basis of their clinical presentation. IGE manifestations include absence seizures, myoclonic jerks and generalized tonic clonic seizures. These may appear alone or in various combinations from patient to patient. In most of the cases, the onset is in early childhood or adolescence although the condition has been observed in adults as well.

Electroencephalogram is the most useful, easy to perform and accessible test for IGE confirmation, although the distinction of different subtypes, especially overlapping ones based on EEG alone may be difficult.

Further research in genetic studies will allow the creation of more accurate classification and discrimination criteria for the various forms of idiopathic generalized epilepsy. Current classification criteria still hinge on identifying the clinical features appropriate for the specific syndrome.

30% of all epilepsy cases are attributed to idiopathic generalized epilepsy (IGE). They are a group of genetic disorders and show no gender or racial predilection. IGE is usually a condition that stays lifelong. Most of the syndromes included in the term IGE start at an early age. Typical clinical manifestations include myoclonic jerks, and generalized tonic-clonic seizures, either alone or in combination with variable severity. The EEG is the laboratory test of choice for IGE. Typical EEG changes include generalized discharges of spikes, polyspikes, or spike/polyspike-waves either ictally or inter-ictally. They could be triggered by episodes of hyperventilation or sleep deprivation. Normal EEG does not exclude the diagnosis IGE. Routine EEG test may be completed by video-EEG or EEG during sleep and awakening if the results obtained are uncertain.

Antiepileptic drugs should be carefully chosen as a few, used in the treatment of focal epilepsies, are contraindicated for IGE. Treatment is often lifelong.

IGEs syndromes included in the lists of the International League Against Epilepsy (ILAE) are: benign myoclonic epilepsy in infancy, epilepsy with myoclonic absences, epilepsy with myoclonic-astatic seizures, epilepsy with generalized tonic–clonic seizures, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and generalized epilepsy with febrile seizures plus. Proper identification of the syndrome based on the clinical features is essential in determining the prognosis of disease. It is hoped that the advent of genetic studies will allow for the creation of more specific classification criteria to aid in prompt diagnosis and prognosis.

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