TY - JOUR
T1 - Unusual white matter involvement in EAST syndrome associated with novel KCNJ10 mutations
AU - Severino, Mariasavina
AU - Lualdi, Susanna
AU - Fiorillo, Chiara
AU - Striano, Pasquale
AU - De Toni, Teresa
AU - Peluso, Silvio
AU - De Michele, Giuseppe
AU - Rossi, Andrea
AU - Filocamo, Mirella
AU - Bruno, Claudio
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Background: Epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) is a rare channelopathy due to KCNJ10 mutations. So far, only mild cerebellar hypoplasia and/or dentate nuclei abnormalities have been reported as major neuroimaging findings in these patients. Methods: We analyzed the clinical and brain MRI features of two unrelated patients (aged 27 and 23 years) with EAST syndrome carrying novel homozygous frameshift mutations (p.Asn232Glnfs*14and p.Gly275Valfs*7) in KCNJ10, detected by whole exome sequencing. Results: Brain MRI examinations at 8 years in Patient 1 and at 13 years in Patient 2 revealed a peculiar brain and spinal cord involvement characterized by restricted diffusion of globi pallidi, thalami, brainstem, dentate nuclei, and cervical spinal cord in keeping with intramyelinic edema. The follow-up studies, performed, respectively, after 19 and 10 years, showed mild cerebellar atrophy and slight progression of the brain and spinal cord T2 signal abnormalities with increase of the restricted diffusion in the affected regions. Conclusion: The present cases harboring novel homozygous frameshift mutations in KCNJ10 expand the spectrum of brain abnormalities in EAST syndrome, including mild cerebellar atrophy and intramyelinic edema, resulting from abnormal function of the Kir4.1 inwardly rectifying potassium channel at the astrocyte endfeet, with disruption of water-ion homeostasis.
AB - Background: Epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) is a rare channelopathy due to KCNJ10 mutations. So far, only mild cerebellar hypoplasia and/or dentate nuclei abnormalities have been reported as major neuroimaging findings in these patients. Methods: We analyzed the clinical and brain MRI features of two unrelated patients (aged 27 and 23 years) with EAST syndrome carrying novel homozygous frameshift mutations (p.Asn232Glnfs*14and p.Gly275Valfs*7) in KCNJ10, detected by whole exome sequencing. Results: Brain MRI examinations at 8 years in Patient 1 and at 13 years in Patient 2 revealed a peculiar brain and spinal cord involvement characterized by restricted diffusion of globi pallidi, thalami, brainstem, dentate nuclei, and cervical spinal cord in keeping with intramyelinic edema. The follow-up studies, performed, respectively, after 19 and 10 years, showed mild cerebellar atrophy and slight progression of the brain and spinal cord T2 signal abnormalities with increase of the restricted diffusion in the affected regions. Conclusion: The present cases harboring novel homozygous frameshift mutations in KCNJ10 expand the spectrum of brain abnormalities in EAST syndrome, including mild cerebellar atrophy and intramyelinic edema, resulting from abnormal function of the Kir4.1 inwardly rectifying potassium channel at the astrocyte endfeet, with disruption of water-ion homeostasis.
KW - Astrocytopathy
KW - Brain MRI
KW - Channelopathy
KW - Diffusion-weighted imaging
KW - EAST syndrome
KW - Frameshift variants
KW - Intramyelinic edema
KW - KCNJ10
KW - Kir4.1
KW - SeSAME syndrome
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85045441415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045441415&partnerID=8YFLogxK
U2 - 10.1007/s00415-018-8826-7
DO - 10.1007/s00415-018-8826-7
M3 - Article
C2 - 29666984
AN - SCOPUS:85045441415
VL - 265
SP - 1419
EP - 1425
JO - Journal of Neurology
JF - Journal of Neurology
SN - 0340-5354
IS - 6
ER -