A Child with a c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 Mutation Associated with a Severe Early Infantile Epileptic Encephalopathy
Department of Systems Medicine, Unit of Child Neurology and Psychiatry, “Tor Vergata” University of Rome, 00133 Rome, Italy
Unità Sanitaria Locale (USL) Umbria 2, Viale VIII Marzo, 05100 Terni, Italy
Paediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Piazza Menghini 1, 06132 Perugia, Italy
Department of Child Neurology and Psychiatry, 47122 Forlì, Italy
Department of Genetics, Santa Maria Hospital, 05100 Terni, Italy
Medical Genetics Unit, S. Maria della Misericordia Hospital, 06132 Perugia, Italy
Università degli Studi di Milano, 20122 Milan, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 1976; https://doi.org/10.3390/ijms19071976
Received: 1 June 2018 / Revised: 2 July 2018 / Accepted: 3 July 2018 / Published: 6 July 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Early infantile epileptic encephalopathies (EIEEs) are a group of neurological disorders characterized by early-onset refractory seizures, severe electroencephalographic abnormalities, and developmental delay or intellectual disability. Recently, genetic studies have indicated that a significant portion of previously cryptogenic EIEEs are single-gene disorders. SPTAN1 is among the genes whose mutations are associated with EIEE development (OMIM# 613477). Here, a case of the c.6923_6928dup (p.Arg2308_Met2309dup) SPTAN1 mutation associated with a severe EIEE is reported. This case shows that mutations in the α20 repeat in the C-terminal of αII spectrin can be associated with EIEE. Duplication seems essential to cause EIEE. This causation is not demonstrated for amino acid deletions in the same spectrin residues. Reportedly, children with p.(Asp2303_Leu2305del) and p.(Gln2304_Gly2306del) deletions have childhood-onset epilepsy and no or marginal magnetic resonance imaging abnormalities, suggesting that not only the location but also the type of mutation plays a role in conditioning nervous system damage. Further studies are needed for a better understanding of the phenotype/genotype correlation in SPTAN1-related encephalopathies.