EurekaMag.com logo
+ Translate

Clinical, neuroimaging, and genetic characteristics of megalencephalic leukoencephalopathy with subcortical cysts in Egyptian patients


, : Clinical, neuroimaging, and genetic characteristics of megalencephalic leukoencephalopathy with subcortical cysts in Egyptian patients. Pediatric Neurology 50(2): 140-148

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. 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. 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 C > T, p.Pro294Ser) was identified in the third family. 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.

(PDF same-day service: $19.90)

Accession: 052136946

PMID: 24315536

DOI: 10.1016/j.pediatrneurol.2013.10.008

Submit PDF Full Text: Here


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Blattner, R.; Von Moers, A.; Leegwater, P.A.J.; Hanefeld, F.A.; Van Der Knaap, M.S.; Köhler, W., 2003: Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC). Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) was recently localized on chromosome 22qtel and 26 different mutations of the gene MLCL have been found. We report three siblings of non-consanguineous parents who presen...

Masuda, T.; Ueda, M.; Ueyama, H.; Shimada, S.; Ishizaki, M.; Imamura, S.; Yamamoto, T.; Ando, Y., 2016: Megalencephalic leukoencephalopathy with subcortical cysts caused by compound heterozygous mutations in MLC1, in patients with and without subcortical cysts in the brain. Journal of the Neurological Sciences 351(1-2): 211-213

Patrono, C.; D.G.acinto, G.; Eymard-Pierre, E.; Santorelli, F.M.; Rodriguez, D.; D.S.efano, N.; Federico, A.; Gatti, R.; Benigno, V.; Megarbané, A.; Tabarki, B.; Boespflug-Tanguy, O.; Bertini, E., 2003: Genetic heterogeneity of megalencephalic leukoencephalopathy and subcortical cysts. Reported are the clinical, neuroradiologic, and molecular findings in 18 patients with megalencephalic leukoencephalopathy and subcortical cysts (MLC) syndrome. Marked clinical intrafamilial and interfamilial variability in mutation-proven cases w...

Wu, W-qing.; Xie, J-sheng.; Han, C-xi.; Xu, Z-yong.; Geng, Q.; Yuan, H., 2012: Genetic analysis and prenatal diagnosis for a family with megalencephalic leukoencephalopathy and subcortical cysts. To identify potential mutation in the MLC1 gene in a Chinese family affected with megalencephalic leukoencephalopathy and subcortical cysts (MLC), and to provide prenatal diagnosis. Genomic DNA of the patients, their parents and younger sister wer...

Saijo, H.; Nakayama, H.; Ezoe, T.; Araki, K.; Sone, S.; Hamaguchi, H.; Suzuki, H.; Shiroma, N.; Kanazawa, N.; Tsujino, S.; Hirayama, Y.; Arima, M., 2003: A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): Molecular genetic study. Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor function with ataxia, spasticity and mental decline. It has been revealed that the mutations...

Saijo, H.; Nakayama, H.; Ezoe, T.; Araki, K.; Sone, S.; Hamaguchi, H.; Suzuki, H.; Shiroma, N.; Kanazawa, N.; Tsujino, S.; Hirayama, Y.; Arima, M., 2003: A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study. Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor function with ataxia, spasticity and mental decline. It has been revealed that the mutations...

Kariminejad, A.; Rajaee, A.; Ashrafi, M.Reza.; Alizadeh, H.; Tonekaboni, S.Hasan.; Malamiri, R.Azizi.; Ghofrani, M.; Karimzadeh, P.; Mohammadi, M.Molla.; Baghalshooshtari, A.; Bozorgmehr, B.; Kariminejad, M.Hasan.; Postma, N.; Abbink, T.E.M.; van der Knaap, M.S., 2015: Eight novel mutations in MLC1 from 18 Iranian patients with megalencephalic leukoencephalopathy with subcortical cysts. Megalencephalic leukoencephalopathy with subcortical cysts (MLC) (MIM #604004) is a rare autosomal recessive neurological disorder characterized by macrocephaly, motor and cognitive decline, ataxia, spasticity and occasional seizures. Magnetic res...

Reis, F.; Kido, R.Yoshio.Zanetti.; Mesquita, Jão.Amaral.; Oshima, M.Mari.; Montenegro, M.Augusta., 2015: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) - a case with clinical and magnetic resonance imaging (MRI) dissociation. Arquivos de Neuro-Psiquiatria 73(2): 171-172

Arnedo, T.; Aiello, C.; Jeworutzki, E.; Dentici, M.Lisa.; Uziel, G.; Simonati, A.; Pusch, M.; Bertini, E.; Estévez, Rúl., 2014: Expanding the spectrum of megalencephalic leukoencephalopathy with subcortical cysts in two patients with GLIALCAM mutations. Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a heterogeneous neurodegenerative leukodystrophy caused by recessive mutations in MLC1 or GLIALCAM (types MLC1 and MLC2A) of by dominant mutations in GLIALCAM (MLC2B). GlialCAM fu...

Xie, H.; Wang, J.; Dhaunchak, A.Singh.; Shang, J.; Kou, L.; Guo, M.; Wu, Y.; Gu, Q.; Colman, D.; Wu, X.; Jiang, Y., 2012: Functional studies of MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts. Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM# 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recentl...