Overview
- Considered an 'epileptic encephalopathy
- Characterized by onset of refractory focal seizures in the first year of life.
- Associated with severe encephalopathy.
- Focal seizures arise independently in both hemispheres.
- Seizures can migrate from one cortical region to another randomly but consecutively in the same seizure.
- Seizures are often prolonged with episodes of status epilepticus.
- Cause:
- Unknown in most cases.
- Few genes recently linked with this syndrome.
- Epileptic activity might directly contribute additional cognitive and behavioral impairments.
- Suppression of epileptic activity might minimize these additional impairments.
Clinical Context
- Typical onset: first six months of life (mean 3 months).
- Prevalence: <1 / 1 000 000
- Later onset in the first year of life has been reported.
- Both sexes equally affected.
- Antecedent and birth history typically normal.
- Head size and neurological examination usually normal at onset.
- Later neurological findings consistent with severe neurological impairment.
- Most patients develop microcephaly by 1 year of age.
- Development:
- May be normal at onset.
- Regression and subsequent severe delay typical.
- Prognosis:
- Poor with ongoing intractable seizures.
- Severe neurological disability and reduced life expectancy.
- Milder evolution reported in a few children.
Seizures
- Focal motor seizures initially sporadic, frequency rapidly increases.
- Focal clonic seizures common (involving arms or eyelids).
- Behavioral arrest with or without head and eye version may occur.
- Migration of focal seizure with involvement of multiple independent cortical regions randomly but consecutively is mandatory.
- Status epilepticus is common.
- Seizures with prominent autonomic features may occur.
EEG
- Background:
- Normal at onset.
- Diffuse slowing of the background occurs over time.
- Focal slow activity may migrate from one brain region to another.
- Interictal:
- Multifocal discharges appear later in all cases.
- Activation:
- EEG abnormality enhanced by sleep deprivation and sleep.
- Ictal:
- Distribution of focal ictal patterns should correlate with clinical features.
- Involvement of multiple independent cortical regions randomly but consecutively in the same seizure or status epilepticus event.
- Ictal discharges typically rhythmic alpha or theta activities.
Imaging
- Normal neuroimaging at outset.
- Follow-up findings may include:
- Mild to moderate enlargement of subarachnoid and ventricular spaces.
- Mesial temporal sclerosis.
- Cerebellar atrophy.
Genetics
- Pattern of Inheritance:
- No familial inheritance reported.
- De novo gene abnormalities implicated.
- Known Genes:
- 70% of children have an identified genetic etiology. Half of them present gain-of-function mutations affecting the KCNT1 gene, located on 9q34.4.
- In other cases the genes involved may include SCN2A (2q24.3), KCNQ2 (20q13.33), PLCB1 (20p12.3), TBC1D24 (16p13.3), PIGA (Xp22.2), SCN1A (2q24.3), SLC25A22 (11p15.5), and SLC12A5 (20q13.12).
- The following genes have been reported in single cases: GABRA1, GABRB1, ATP1A3, CDKL5, and ITPA.
- Family History of Seizures/Epilepsy:
- Not typical.
- Rare cases reported with a family history of epilepsy or febrile convulsions.
Differential Diagnosis
- Dravet Syndrome
- other epileptic and developmental encephalopathies starting during the neonatal period, in particular when multifocal seizures and EEG abnormalities are present.
References
Orphanet. (n.d.). Malignant Migrating Focal Seizures of Infancy. Retrieved June 1, 2024, from https://www.orpha.net/en/disease/detail/293181
