RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss—Another Mendelian Mimicker of Congenital Cytomegalovirus Infection

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• 作者：Nicole Ulrick ; BA^a ; Amy Goldstein ; MD^b ; Cas Simons ; PhD^c ; Ryan J. Taft ; PhD^c ; ^d ; ^e ; Guy Helman ; BS^a ; Amy Pizzino ; MS ; CGC^a ; Miriam Bloom ; MD^a ; Julie Vogt ; MBBS ; MRCP^f ; Karen Pysden ; MD^g ; Daria Diodato ; MD^h ; Diego Martinelli ; MDⁱ ; Ahmad Monavari ; MD^j ; Daniela Buhas ; MD^k ; ^l ; Clara D.M. van Karnebeek ; MD ; PhD^m ; Imen Dorboz ; PhDⁿ ; Odile Boespflug-Tanguy ; MD ; PhDⁿ ; ^o ; Diana Rodriguez ; MD ; PhDⁿ ; ^p ; ^q ; Martine Té ; treault ; PhD^l ; ^r ; Jacek Majewski ; PhD^l ; ^r ; Genevieve Bernard ; MD ; MSc^k ; ^s ; ^t ; ^u ; Yi Shiau Ng ; MRCP^v ; Care4Rare Canada Consortium
• 刊名：Pediatric Neurology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：66
• 期：Complete
• 页码：59-62
• 全文大小：409 K
• 卷排序：66

文摘

Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi–Goutières 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.MethodsWe 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 neuroradiological features.ResultsMRI 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.ConclusionsDespite 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.