Olivier et al. (1998) described 3 Turkish children, including 2 sibs, with cystic leukoencephalopathy observed on brain MRI. Neurologic deficits were noted within the first months of life, and included severe intellectual impairment, motor retardation, and spasticity. Brain ... Olivier et al. (1998) described 3 Turkish children, including 2 sibs, with cystic leukoencephalopathy observed on brain MRI. Neurologic deficits were noted within the first months of life, and included severe intellectual impairment, motor retardation, and spasticity. Brain MRI showed extensive cysts within the anterior temporal lobes, ventricular enlargement, and white matter disease. The signal intensities of the cysts were identical to those of cerebrospinal fluid. Screening for known inborn errors of metabolism, especially those characterized by white matter involvement, did not reveal any abnormality. Gomes et al. (2001) reported 2 patients with a 'peculiar leukoencephalopathy with temporal cysts.' Both had a nonprogressive neurologic disorder with mental retardation, microcephaly, and sensorineural deafness. Metabolic disorders with white matter involvement and leukoencephalopathy with vanishing white matter disease (VWM; 603896) were excluded based on clinical, biologic, and imaging findings. Cytomegalovirus infection was considered a possibility in the first case. Gomes et al. (2001) noted the phenotypic similarities to the patients reported by Olivier et al. (1998). Henneke et al. (2005) reported 15 white infants, including 2 sibs and 2 first cousins, with early onset of severe psychomotor impairment associated with nonprogressive encephalopathy. MRI showed bilateral cysts in the anterior temporal lobe and white matter lesions with pericystic abnormal myelination and symmetric lesions in the periventricular regions. Central white matter structures were spared. Some had ventricular enlargement. Six patients were normocephalic, and 9 had microcephaly. Most achieved walking with aid, but some could only sit or crawl, and most lacked speech development. Other variable features included seizures, spasticity, athetoid hand movements, dystonia, nystagmus, and hearing loss. Three of the children were described as having a 'doll-like face.' The course of the disease was stable or very slowly progressive. Henneke et al. (2009) reported 7 patients from 5 families with infantile-onset cystic leukoencephalopathy. Affected individuals were asymptomatic at birth but showed a static encephalopathy with normo- or microcephaly and psychomotor impairment within the first year of life, accompanied by seizures and sensorineural hearing impairment. Screening for known inborn or infectious diseases was either negative or inconclusive. Brain MRI showed bilateral anterior temporal lobe cystic lesions and enlarged inferior horns combined with multifocal white matter alterations. CT scans showed intracranial calcifications in some subjects. Five of the patients were over age 10 years at the time of the report, and all showed delayed psychomotor development with a variable ability to sit or walk with or without aid. Speech was often poor. The phenotype could not be differentiated from neonatally asymptomatic congenital CMV brain infection.
By linkage analysis and candidate gene sequencing in 2 consanguineous Turkish families with cystic leukoencephalopathy without megalencephaly, Henneke et al. (2009) identified 2 different homozygous mutations in the RNASET2 gene (612944.0001 and 612944.0002, respectively) that segregated with the ... By linkage analysis and candidate gene sequencing in 2 consanguineous Turkish families with cystic leukoencephalopathy without megalencephaly, Henneke et al. (2009) identified 2 different homozygous mutations in the RNASET2 gene (612944.0001 and 612944.0002, respectively) that segregated with the disorder. Analysis of 3 additional unrelated individuals with the disorder identified homozygous or compound heterozygous RNASET2 mutations (612944.0003-612944.0006).