The structural brain correlates of cognitive deficits in adults with Klinefelter's syndrome.

CONTEXT: Adults with Klinefelter's syndrome (KS) are known to present disturbances of language skills and delayed learning abilities. OBJECTIVES: The aim of this study was to assess brain morphometry in KS and to correlate eventual volumetric changes with performance on neuropsychological tests. PATIENTS: Patients included 18 KS adults and 20 age-matched controls. METHODS: All participants underwent prospectively double-spin-echo brain magnetic resonance imaging and neuropsychological testing of verbal and nonverbal domains. On the axial stack of magnetic resonance imaging slices, regional brain volumes were measured either by automated segmentation (full brain, total cerebrospinal fluid, and ventricular volume) or manual drawing with help of a neuroanatomy atlas (frontal, temporal, and parietal lobes, gray matter component of the lobes, cerebellar hemispheres, and hippocampal complexes). RESULTS: KS patients performed significantly lower than controls on language-related tasks exploring verbal processing speed and verbal executive function. They were diagnosed with significant enlargement of ventricular volume and bilateral reduction of cerebellar hemispheres. Furthermore, after separation of participants according to handedness and after correction of regional brain volumes for atrophy, a significant reduction of left temporal lobe volume was found in KS compared with controls. Ventricular volume was inversely correlated with cognitive function, whereas left temporal lobe volume was positively correlated with language-related tasks. CONCLUSION: This study hypothesizes that supernumerary X-chromosome and/or congenital hypogonadism provoke structural alterations in the subcortical pathways involved in language processing, thus providing a neurobiological substrate for cognitive deficits in KS.

Klinefelter's syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray.

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed "anomalous dominance," is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes.

Premature menarche--a legend or a defined clinical syndrome.

The properness of diagnosing the premature menarche as isolated clinical syndrome is often questioned. A long-term observation od 2 girls with premature menarche has been described. A discussion is presented about the role of imbalance within the hypothalamus-pituitary-gonads axis and the role of disturbances in peripheral responsiveness to sex hormones in the patho-mechanism of premature menarche.