GeneReviews®

Related Articles

GeneReviews®

Book. 1993

Authors: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A

Abstract
CLINICAL CHARACTERISTICS: SLC12A5-related epilepsy of infancy with migrating focal seizures (SLC12A5-EIMFS), reported to date in nine children, is characterized by onset of seizures before age six months and either developmental delay or developmental regression with seizure onset. Of these nine children, six had severe developmental delay with no progress of abilities and three made notable neurodevelopmental progress. Eight had postnatal microcephaly and hypotonia. In most children epilepsy begins as focal motor seizures (typically involving head and eye deviation) that become multifocal and intractable to conventional antiepileptic drugs (AEDs).
DIAGNOSIS/TESTING: The diagnosis of SLC12A5-EIMFS is established by identification of biallelic SLC12A5 pathogenic variants on molecular genetic testing.
MANAGEMENT: Treatment of manifestations: There are no specific treatments for seizures in SLC12A5-EIMFS. In general, seizures in EIMFS are resistant to most AEDs. A ketogenic diet and potassium bromide showed attenuation of seizures in three patients each. A multidisciplinary approach to management of hypotonia, feeding difficulties, respiratory problems, and developmental delay is recommended. Surveillance: Routine monitoring of: feeding, nutritional status, swallowing, gastroesophageal reflux, aspiration, and respiratory problems; back for scoliosis and hips for dislocation with spine and hip x-rays; effectiveness of seizure control; development including motor skills, speech/language, and general cognitive and vocational skills.
GENETIC COUNSELING: SLC12A5-EIMFS is inherited in an autosomal recessive manner. The parents of a child with SLC12A5-EIMFS are typically heterozygotes (i.e., carriers of one SLC12A5 pathogenic variant). Heterozygous parents of a child with SLC12A5-EIMFS are not at risk of developing EIMFS. When both parents are heterozygotes (carriers) each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SLC12A5 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic diagnosis are possible.

PMID: 30763027

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