Epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome in a European child with KCNJ10 mutations: A case report

Abstract

Background:Epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome is a multi-organ disorder that links to autosomal recessive mutations in the KCNJ10 gene, which encodes for the Kir4.1 potassium channel. It is mostly described in consanguineous, non-European families.Case Report:A European male of non-consanguineous birth, with early-onset, static ataxic motor disorder, intellectual disability and epilepsy, imitating cerebral palsy, presented with additional findings of renal tubulopathy, sensorineural deafness and normal neuroimaging leading to the diagnosis of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome. The patient was heterozygous for two KCNJ10 mutations: a missense mutation (p.R65C) that is already published and a not yet published duplication (p.F119GfsX25) that creates a premature truncation of the protein. Both mutations are likely damaging. Parental testing has not been performed, and therefore, we do not know for certain whether the mutations are on different alleles. This young man presents some clinical and laboratory features that differ from previously reported patients with epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome.Conclusion:The necessity of accurate diagnosis through genetic testing in patients with static motor disorders resembling cerebral palsy phenotypes, atypical clinical features and noncontributory neuroimaging is emphasized.

EAST/SeSAME syndrome: Review of the literature and introduction of four new Latvian patients

“…In this study, we report a novel family of 4 siblings (1 male, 3 females, 2‐9 years of age at the time of publication) with EAST/SeSAME syndrome and a KCNJ10 mutation homozygous for R65C. This mutation was previously found in a boy with EAST syndrome who was born of consanguineous Algerian parents and a Greek boy who was born of nonconsanguineous parents . The mutation affects the same amino acid as the one discussed before (R65P) and may have the same pathogenic mechanism involved.…”

“…Our patients experienced several seizure patterns, suggestive of focal onset. Currently, 5 patients are reported to be seizure‐free, and 6 patients have either developed focal seizures or continue to have GTCS when unwell (3 of them had a remission followed by re‐emergence of seizures; Table ). Two cases of status epilepticus—convulsive and nonconvulsive—and a case of prolonged seizure activity leading to right‐sided hemiparesis have been described as well.…”

“…The information on patients’ development is scarce and often described as “delayed.” Nevertheless, as outlined in detail (Table ), 4 patients attended a special school, and 2 patients attended a mainstream school albeit having a moderate level of learning problems . Cognitive and learning difficulties have been found in several patients; there seems to be no loss of skills, but the progress in cognitive function is slower than in peers …”

“…In our patients, the 2 eldest children presented with hypotonia only early in their childhood. When neurological findings were described (Table ), both hypertonia (generalized or exclusively in lower limbs) and hypotonia were mentioned equally. Several upper neuron changes included brisk or exaggerated reflexes (6 patients), ankle clonus, positive Babinski sign (in each of 3 cases), and spasticity .…”

“…When neurological findings were described (Table ), both hypertonia (generalized or exclusively in lower limbs) and hypotonia were mentioned equally. Several upper neuron changes included brisk or exaggerated reflexes (6 patients), ankle clonus, positive Babinski sign (in each of 3 cases), and spasticity . Decreased superficial feeling, nystagmus, and dystonia were reported as well.…”