TY - JOUR
T1 - RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection
AU - Ulrick, Nicole
AU - Goldstein, Amy
AU - Simons, Cas
AU - Taft, Ryan J.
AU - Helman, Guy
AU - Pizzino, Amy
AU - Bloom, Miriam
AU - Vogt, Julie
AU - Pysden, Karen
AU - Diodato, Daria
AU - Martinelli, Diego
AU - Monavari, Ahmad
AU - Buhas, Daniela
AU - van Karnebeek, Clara D. M.
AU - Dorboz, Imen
AU - Boespflug-Tanguy, Odile
AU - Rodriguez, Diana
AU - Tétreault, Martine
AU - Majewski, Jacek
AU - Bernard, Genevieve
AU - Ng, Yi Shiau
AU - McFarland, Robert
AU - Vanderver, Adeline
PY - 2017
Y1 - 2017
N2 - BACKGROUND: Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutieres syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection. METHODS: We reviewed a large-scale biorepository of patients with unsolved leukodystrophies and identified two individuals with required for meiotic nuclear division 1 (RMND1) mutations and similar magnetic resonance imaging (MRI) features, including temporal lobe cysts. Ten additional subjects with confirmed RMND1 mutations were identified as part of a separate disease specific cohort. Brain MRis from all 12 individuals were reviewed for common neuroradielogical features. RESULTS: MRI features in RMND1 mutations included temporal lobe swelling, with rarefaction and cystic evolution, enlarged tips of the temporal lobes, and multifocal subcortical white matter changes with confluent periatrial T2 signal hyperintensity. A combination of these features was present in ten of the 12 individuals reviewed. CONCLUSIONS: Despite the small number of reported individuals with RMND1 mutations, a clinically recognizable phenotype of leukoencephalopathy with temporal lobe swelling, rarefaction, and cystic changes has emerged in a subset of individuals. Careful clinical phenotyping, including for lactic acidosis, deafness, and severe muscle involvement seen in RMND1 mutation positive individuals, and MRI pattern recognition will be important in differentiating these patients from children with congenital infections like cytomegalovirus
AB - BACKGROUND: Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutieres syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection. METHODS: We reviewed a large-scale biorepository of patients with unsolved leukodystrophies and identified two individuals with required for meiotic nuclear division 1 (RMND1) mutations and similar magnetic resonance imaging (MRI) features, including temporal lobe cysts. Ten additional subjects with confirmed RMND1 mutations were identified as part of a separate disease specific cohort. Brain MRis from all 12 individuals were reviewed for common neuroradielogical features. RESULTS: MRI features in RMND1 mutations included temporal lobe swelling, with rarefaction and cystic evolution, enlarged tips of the temporal lobes, and multifocal subcortical white matter changes with confluent periatrial T2 signal hyperintensity. A combination of these features was present in ten of the 12 individuals reviewed. CONCLUSIONS: Despite the small number of reported individuals with RMND1 mutations, a clinically recognizable phenotype of leukoencephalopathy with temporal lobe swelling, rarefaction, and cystic changes has emerged in a subset of individuals. Careful clinical phenotyping, including for lactic acidosis, deafness, and severe muscle involvement seen in RMND1 mutation positive individuals, and MRI pattern recognition will be important in differentiating these patients from children with congenital infections like cytomegalovirus
U2 - https://doi.org/10.1016/j.pediatrneurol.2016.09.003
DO - https://doi.org/10.1016/j.pediatrneurol.2016.09.003
M3 - Article
C2 - 27843092
SN - 0887-8994
VL - 66
SP - 59
EP - 62
JO - Pediatric neurology
JF - Pediatric neurology
ER -