Clinical Guidance

No clear correlation exists between biallelic SLC12A5 variants and phenotype, which may reflect the limited number of affected individuals reported to date.

Source: GeneReviews — "SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures"

Diagnostic Criteria

Since 2010 a description of the characteristic symptoms and findings of epilepsy of infancy with migrating focal seizures (EIMFS) has been included in the classification of epilepsy syndromes by the International League Against Epilepsy. The diagnosis of SLC12A5-EIMFS is established by molecular genetic testing.

Suggestive Findings

SLC12A5-related epilepsy of infancy with migrating focal seizures (SLC12A5-EIMFS) should be considered in children with the following epilepsy and electroencephalogram (EEG) findings and family history.

Epilepsy features

• Seizure onset before age six months

• Developmental delay or developmental regression with seizure onset

Seizure type

Source: GeneReviews — "SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures"

Differential Diagnosis

Since first described by , epilepsy of infancy with migrating focal seizures (EIMFS) has been reported in over 170 individuals. EIMFS is genetically heterogeneous. EIMFS can be isolated or have multisystem involvement; both autosomal dominant and recessive inheritance are observed.

Table 2.

Other Disorders to Consider in the Differential Diagnosis of SLC12A5-EIMFS

Disorder | Gene1 | MOI | Comments

Isolated EIMFS

EIEE43(OMIM 617113) | GABRB32 | AD | 1 set of monozygotic twins

EIEE14(OMIM 614959) | KCNT1 | AD3 | Causes 30%-50% of EIMFS4,5,6

EIEE12(OMIM 613722) | PLCB17 | AR8 | 1 individual7

Progressive microcephalyw/seizures cerebral cerebellar atrophy(OMIM 615760) | QARS | AR8 | 2 individuals9

SMC1A-related EIMFS | SMC1A10 | XL | 1 female infant

EIEE6

| SCN1A11,12,13,14 | AD3 | 3 individuals11,12,13,1...

Source: GeneReviews — "SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SLC12A5-related epilepsy of infancy with migrating focal seizures (SLC12A5-EIMFS), the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with SLC12A5-EIMFS

Source: GeneReviews — "SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures"

Surveillance Guidelines

Routine monitoring of:

• Feeding, nutritional status, swallowing abilities, gastroesophageal reflux, risk of aspiration pneumonia / respiratory infection

• Postural problems (resulting from such complications as scoliosis and hip abnormalities) with regular spine and hip x-rays

• Effectiveness of seizure control

• Development including motor skills, speech/language, and general cognitive and vocational skills

Source: GeneReviews — "SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures"