- 作者：Iman G. Mahmoud ; Marwa Mahmoud ; Miral Refaat ; Marian Girgis ; Nevin Waked ; Ameera El Badawy ; Laila Selim ; Sawsan Hassan ; Alice K. Abdel Aleem
- 关键词：Van der Knaap disease ; macrocephaly ; megalencephalic leukodystrophy ; subcortical cysts ; MLC1 gene ; GliaCAM gene ; developmental delay
- 刊名：Pediatric Neurology
- 出版年：February, 2014
- 年：2014
- 卷：50
- 期：2
- 页码：140-148
- 全文大小：1914 K
Background
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare and genetically heterogeneous cerebral white matter disease. Clinically, it is characterized by macrocephaly, developmental delay, and seizures. We explore the clinical spectrum, neuroimaging characteristics, and gene involvement in the first patients with megalencephalic leukoencephalopathy with subcortical cysts described from Egypt.Patients
Six patients were enrolled from three unrelated families. Patient inclusion criteria were macrocephaly, developmental delay, normal urinary organic acids, and brain imaging of diffuse cerebral white matter involvement. Direct sequencing of the MLC1 gene in patients' families and GliaCAM in one questionable case was performed using BigDye Terminator cycle sequencing.
Results
Clinical heterogeneity, both intra- and interfamilial, was clearly evident. Developmental delays ranged from globally severe or moderate to mild delay in achieving walking or speech. Head circumference above the ninety-seventh percentile was a constant feature. Neuroimaging featured variability in white matter involvement and subcortical cysts. However, findings of posterior fossa changes and brain stem atrophy were frequently (66.6%) identified in these Egyptian patients. Discrepancy between severe brain involvement and normal mental functions was evident, particularly in patients from the third family. MLC1 mutations were confirmed in all patients. Deletion/insertion mutation in exon 11 (c.908-918delinsGCA, p.Val303 Gly fsX96) was recurrent in two families, whereas a missense mutation in exon 10 (c.880聽C聽>聽T, p.Pro294Ser) was identified in the third family.
Conclusions
This report extends our knowledge of the clinical and neuroimaging features of megalencephalic leukoencephalopathy with subcortical cysts. It confirms the apparent lack of selective disadvantage of MLC1 mutations on gamete conception and transmission as supported by the presence of multiple affected siblings in Egyptian families.