Fragile X syndrome (FRAXA) is the most common form of inherited mental retardation. The syndrome is caused by a CGG-expansion mutation in the gene FMR-1, located at Xq27.3. The morphologic anomalies in this syndrome can be subtle: elongated face, large ears, and macro-orchidism. More striking is the neurobehavioral phenotype: cognitive dysfunction, hyperactivity, distractability, lack of impulse control, perseveration, social deficits, communication abormalities, and autistic behaviors [Hagerman et al., 1991], similar to behaviors seen in attention deficit and hyperactivity disorder (ADHD) and Tourette syndrome. Neuroimaging with MRI has shown decreased size of the cerebellar vermis, increased size of the lateral ventricles, greater hippocampal area, and increased volume of the caudate nuclei as compared to normal controls [Reiss et al., 1995].
ADHD was the first behavior disorder attributed to dysfunction in the frontal lobe-subcortical circuit. Since then a number of disorders such as Tourette syndrome, schizophrenia, and obsessive compulsive disorder have joined the list [Lou, 1992]. With the discovery of morphological abnormalities of the caudate nuclei we hypothesize that FRAXA may be in part attributable to a dysfunction in the frontal-subcortical circuit as well. Functional investigations with neuroimaging methods have not previously been published. The present report communicates the result of a pilot study with SPECT CBF using 99 m -Tc-HMPAO as tracer.
The patients were five males and one female (age 16 months to 38 years) with FRAXA. The investigation was approved by the regional ethics committee. A dedicated brain SPECT camera, Ceraspect (DSI, Waltham, MA), was used. The scintigraphy was analyzed using a standard regional analysis program (Nycomed-Amersham shareware v. 1.1). The program analyzes consecutive transaxial slices of 1 cm thickness starting at the orbito-meatal plane. The output is in percentages: weighted counts of regions of interest (ROI)/ weighted counts of a relevant reference region (whole *