Volumetric MRI analyses of the cerebral cortex and posterior fossa of 20 girls with Rett syndrome (RS) were compared with individually-matched normal controls at the Kennedy Krieger Institute, The Johns Hopkins University School of Medicine, Baltimore, MD. Gray and white-matter tissue volumes, with the exception of the pons, showed reductions in RS compared to controls. The caudate nucleus showed a disproportionate volume reduction. A reduction in cerebellar measurements followed the general reduction in brain size in RS. Age-related changes were not different from controls, and a progressive neurodegeneration was not evident. Brains of monozygotic twins discordant for RS revealed reduced gray-matter volumes in the RS twin but not in her sister. [1]

COMMENT. These volumetric neuroanatomical studies of Rett syndrome are important in our understanding of developmental and clinical-anatomical correlations. The etiology of RS remains an enigma, and even the genetics of the disorder are undetermined. My colleague, Dr John Wilson, in his introduction to a chapter on RS in Vol III, Progress in Pediatric Neurology, 1997, suggests the process of apoptosis as a possible explanation for RS.

Apoptosis in development and disease of the nervous system: 1. Naturally occurring cell death in the developing nervous system, is discussed by Narayanan V, University of Pittsburgh, PA [2]. The occurrence of cell degeneration during normal neural development has been studied experimentally in chick embryos, and apoptosis is proposed as the mechanism of infantile spinal muscular atrophy. Substances produced by the target tissue influence the survival of developing neurons. Limb bud removal causes cell degeneration in brachial or lumbosacral ganglia. In Rett syndrome, the neurons may be genetically defective.

The differentiation of infantile autism and Rett syndrome may be difficult in infancy. The head size can be an important diagnostic indicator. Macrocephaly in children and adults with autism is reported from the University of Utah Neuropsychiatric Institute, Salt Lake City, UT [3]. In 14% of 91 subjects with autism, the head circumference was above the 97th percentile at a mean age of 14 years (range, 3 to 38 years), even when corrected for height; macrocephaly was usually not present at birth. Accelerated head growth occurs after 4 years of age in 37% of children with autism. MRI studies were mostly normal.