Neonatal Alexander Disease: MR Imaging Prenatal Diagnosis ========================================================= * E. Vázquez * A. Macaya * N. Mayolas * S. Arévalo * M.A. Poca * G. Enríquez ## Abstract **SUMMARY:** Alexander disease (AD) is a rare neurodegenerative disorder characterized by megalencephaly, leukoencephalopathy, and Rosenthal fibers within astrocytes. This report describes the case of a female patient with sonography-detected ventriculomegaly at 32 weeks’ gestation and distinctive MR imaging features at 33 and 36 weeks’ gestation, at birth, and at 2 months of age, which led to the suggested diagnosis of Alexander disease. Molecular analysis confirmed a missense mutation in the *GFAP* gene. The literature contains little information on the fetal MR imaging findings that may allow prenatal diagnosis of AD. Alexander disease (AD) is an uncommon neurological disorder with 3 clinical subgroups: infantile, juvenile, and adult. The most distinctive histologic feature of AD is the presence of countless Rosenthal fibers throughout the CNS. The genetic basis is presence of mutations in the glial fibrillary acidic protein (*GFAP*) gene, which encodes *GFAP*, located on chromosome 17q21.1 Although characteristic neuroradiologic hallmarks of the infantile subtype of AD have been described,2 prenatal findings had never been previously reported. Presence of prenatal hydrocephalus and abnormal frontal white matter make us rule out AD. ## Case Report A 31-year-old primipara woman was referred to the MR imaging unit from the fetal medicine department to investigate fetal ventriculomegaly discovered on a routine sonography study. The first MR imaging examination performed at 33 weeks’ gestation (Fig 1) showed asymmetric ventricular enlargement, questionable abnormal white matter, and slightly swollen fornices. The second MR imaging examination performed at 36 weeks’ gestation (Fig 2) showed abnormal hyperintense frontal white matter on T1-weighted images, with a low signal intensity on T2-weighted images; a more evident pseudomass was also seen corresponding to the thickened fornices. The definite diagnosis could not be established, and the child was born at 37 weeks by cesarean delivery, with normal birth parameters. A neonatal MR imaging examination was performed at 2 days of life (Fig 3). The diagnosis of AD was strongly suggested on the basis of the imaging findings. AD was confirmed by molecular genetic analysis, which revealed a previously reported1 missense mutation in exon 1 of the *GFAP* gene, producing a 73Met