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Pendred Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
There is tangible evidence that mutations in the FOXI1 gene on chromosome 5q35.1 encoding forkhead box protein I1 and the KCNJ10 gene on chromosome 1q23.2 encoding the ATP-sensitive inward rectifier potassium channel 10 may be implicated in about 2% of non-classic Pendred syndrome (also known as nonsyndromic enlarged vestibular aqueduct [NSEVA]), but not classic Pendred syndrome. Further, biallelic KCNJ10 pathogenic variants are involved in SeSAME syndrome (seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance) and EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) [17,18].
Potassium channels as prominent targets and tools for the treatment of epilepsy
Published in Expert Opinion on Therapeutic Targets, 2021
Mutations of inward rectifying channels are relatively rare in epileptic patients and mostly involve astrocytic Kir4.1. Kir4.1 channels are expressed primarily in astrocytes and support the spatial buffering of potassium. The missense variations in Kir4.1 lead to disruption of astrocyte-dependent spatial buffering of potassium and its pathological accumulation, suggesting a potential mechanism of seizure susceptibility [104]. Loss-of-function mutations in KCNJ10 gene encoding Kir4.1 channel was linked to EAST (epilepsy, ataxia, sensorineural deafness, and tubulopathy) syndrome [105]. Brain abnormalities in EAST syndrome include mild cerebellar atrophy and intramyelinic edema, which may be important diagnostic clues for suspecting this condition in MRI [106]. Single nucleotide polymorphisms of genes encoding Kir4.1 subunits were found in patients with focal and generalized epilepsies including TLE [104,107]. Reduction in glial Kir4.1 function without alterations in activity of Kv channels was found in the tissue of patients with intractable epilepsy and hippocampal sclerosis [108,109]. Mutations of Kir4.1 channels have been detected in patients with the autism-epilepsy phenotype [110], suggesting that dysfunction of the channels may be a common mechanism contributing to seizures and behavioral features of Autism Spectrum Disorders. Mutations in Kir6.2 (KATP) channels are associated with DEND syndrome (infantile diabetes, developmental delay and epilepsy) [111–113].
Novel mutation in the KCNJ10 gene in three siblings with seizures, ataxia and no electrolyte abnormalities
Published in Journal of Neurogenetics, 2018
Muna A. Al Dhaibani, Ayman W. El-Hattab, Kathryn B. Holroyd, Jennifer Orthmann-Murphy, Valerie A. Larson, Khurram A. Siddiqui, Miklos Szolics, Nicoline Schiess
The early onset of seizure activity in infancy is consistent with the majority of EAST syndrome presentations. All three probands had seizures starting in infancy either afebrile focal seizures followed by generalized seizures or afebrile generalized seizures. All three had seizure cessation between ages 4 and 7 years and re-emergence in later years with focal semiology and focal EEG abnormalities.