RECOGNIZABLE INHERITED SYNDROME OF PROGRESSIVE CENTRAL-NERVOUS-SYSTEMDEGENERATION AND GENERALIZED INTRACRANIAL CALCIFICATION WITH OVERLAPPING PHENOTYPE OF THE SYNDROME OF AICARDI AND GOUTIERES

Five boys and two girls from a large consanguineous British Muslim fam ily of Pakistani origin are described. All presented from infancy to e arly childhood with progressive moderate to severe developmental delay , postnatal microcephaly, spastic quadriplegia, refractory seizures, a nd visual handicap. Cerebrospinal fluid (CSF) pleocytosis was present in three children. Neuroimaging with computerized tomography on three boys and a girl showed generalized cortical atrophy, dilatation of the lateral, third, and fourth ventricles, widening of the surface CSF sp aces, hypoplasia of the posterior fossa structures, and multiple and s olitary calcifications in the cerebral cortex and punctate calcificati ons involving basal ganglia, cerebellum, and the Sylvian fissure. Hist opathological examination of the brain from three boys and one girl co nfirmed generalized cortical and cerebellar atrophy with widespread ca lcifications within the cortical grey and white matter, the basal gang lia, the cerebellum, and in some areas along the capillaries. Investig ations excluded a possible nongenetic cause. Parental consanguinity fa vor autosomal recessive inheritance. This appears to be a recognizable syndrome overlapping the syndrome of Aicardi and Goutieres (MIM 22575 0).