Epileptic Encephalopathy, Early Infantile, 15

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

CDKL5, ARX, STXBP1, TSC2, SPTAN1, SCN2A, GRIN2B, ST3GAL3, CNPY3, PLCB1, PHACTR1, SIK1, PIGA, POMC, GUF1, NTRK2, MAGI2, TSC1, CRH, WDR45, HSD17B4, UPB1, AIMP2, TBCD, ABAT, CFL1, ND1, ALG13, SLC35A2, CASK, NEUROD2, TRNW, TRNV, TRNL1, TRNK, PNKP, ND6, ND5, PIGQ, ND4, ND3, ND2, ZNHIT3, ATP6, HIBCH, PIGP, KIF1A, RFT1, CLCN4, KCNA1, TRIM8, SLC19A3, NGLY1, IFNG, TUBA8, SLC25A22, GNAO1, KCNQ2, CRHR1, GABRB3, HTC2, MECP2, FOXG1, NR3C1, MC2R, KCNJ6, NR2F1, PAFAH1B1, SCN1A, PIGW, HNRNPU, TBC1D24, IARS2, BRWD3, HDAC4, KCNT2, KPNA7, DEPDC5, WDR62, AKT3, CPP, PRRT2, UBA5, PDCD6IP, ARFGEF2, TIMM50, FARS2, ATG10, TLK2, SORCS3, TBL1XR1, KCNT1, ARC, PARS2, RARS2, MBD5, PNPO, AARS1, PTCH1, KCNAB2, DLX5, GNB1, GABRB2, GABRA1, MTOR, FLNA, FGF12, FBN1, DPYS, DNMT3A, DNM1, DLG3, YWHAG, DCX, CTNNB1, CSNK1E, CHD2, CACNA2D1, C5AR1, C5, BTD, APC, ACTB, GRIN1, GRIN2A, IGF1, IL2RG, TWIST1, TCOF1, SPTBN2, SOS1, SLC6A4, SLC1A4, SKI, SCN3A, ATXN2, RASGRF1, PPP1CB, PMM2, ABCB1, PDHA1, NGF, NDP, MEF2C, MC4R, LAMA2, KCNJ11, ITGA2B, LINC02210-CRHR1

Drugs

(1S,3S)-3-amino-4-(difluoromethylene) cyclopentanecarboxylic acid hydrochloride, Cannabidiol ( EPIDIOLEX, EPIDYOLEX )

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A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-15 (EIEE15) is caused by homozygous mutation in the ST3GAL3 gene (606494) on chromosome 1p34. One such family has been reported.

For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).

Clinical Features

Edvardson et al. (2013) reported a consanguineous Palestinian family in which 4 members had a severe early infantile epileptic encephalopathy consistent with West syndrome. The patients developed infantile spasms, mainly of the flexor type, between 3 and 7 months of age, which were accompanied by hypsarrhythmia on EEG. Other features included poor eye contact, hypotonia, primitive reflexes, and irritability. As the patients grew older, the seizures continued and evolved clinically to Lennox-Gastaut syndrome. The patients showed developmental delay in the first few months of life, even predating the seizure disorder. At ages 2 to 16 years, all were profoundly mentally retarded and unable to speak or walk independently.

Inheritance

The transmission pattern of EIEE15 in the family reported by Edvardson et al. (2013) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 4 members of a consanguineous Palestinian family with early infantile epileptic encephalopathy-15, Edvardson et al. (2013) identified a homozygous mutation in the ST3GAL3 gene (A320P; 606494.0003). The mutation was identified by linkage analysis combined with whole-exome sequencing of 1 individual and confirmed by Sanger sequencing. The mutation affected the highly conserved sialyl motif S, which is crucially involved in binding of both donor and acceptor substrate. In vitro functional expression studies showed that secretion of the mutant protein was reduced to 25% of control levels and that it had no detectable enzymatic activity. Edvardson et al. (2013) noted that the phenotype was more severe than that observed by Hu et al. (2011), who had identified ST3GAL3 mutations outside of the highly conserved and functionally important sialyl motifs in patients with autosomal recessive nonsyndromic mild to moderate mental retardation-12 (MRT12; 611090).