The effects of X monosomy on brain development: Monozygotic twins discorcant for Turner's syndrome

Abstract

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal-occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.

Fragile-X: neuropsychological test performance, CGG triplet repeat lengths, and hippocampal volumes.

“…The same studies also reported an unexplained enlargement of the parahippocampal gyrus in Down's syndrome (44,45). In Turner's syndrome, the size of the hippocampus has also been reported to be diminished (46).…”

Three Parietal Circuits for Number Processing

“…A positron emission tomography study of five adult women demonstrated a glucose hypometabolism in bilateral parietal and occipital regions (Clark, Klonoff, & Hadyen, 1990). Two anatomical MR studies, one with 18 and the other with 30 affected women, demonstrated bilateral reductions in parieto-occipital brain volume, together with other subcortical regions (Murphy et al, 1993; see also Reiss et al, 1993;Reiss, Mazzocco, Greenlaw, Freund, & Ross, 1995). Interestingly, the phenotype of Turner syndrome can differ depending on whether the remaining X chromosome is of paternal or maternal origin (Xm or Xp subtypes; Bishop, Canning, Elgar, Morris, Jacobs, & Skuse, 2000;Skuse, 2000;Skuse et al, 1997).…”

A cognitive characterization of dyscalculia in Turner syndrome

“…A positron emission tomography study of five adult women demonstrated a glucose hypometabolism in bilateral parietal and occipital regions (Clark, Klonoff, & Hadyen, 1990). Two anatomical MR studies also demonstrated bilateral reductions in parieto-occipital brain volume, together with several other cortical and subcortical regions (Murphy et al, 1993;Reiss et al, 1993;Reiss, Mazzocco, Greenlaw, Freund, & Ross, 1995).…”