The proceedings of the 9th International Workshop on Fragile X Syndrome and X-Linked Mental Retardation, held in Strasbourg, France, are reported from the University Hospital of Leuven, Belgium.

Several examples of X-Linked MR syndromes were presented. Mohr-Tranebjaerg syndrome (MTS), characterized by deafness, dystonia and mental retardation (MR), was discussed as a mitochondrial disorder with a gene named DDP for deafness/dystonia peptide. Among a set of 8 patients with MTS, only one of 4 studied showed ragged-red fibers on muscle biopsy whereas 4/4 had increased numbers of mitochondria.

In two papers on fragile X syndrome (FXS), a total of 27 children (24 boys and 3 girls), the diagnosis had been missed by the referring physicians. Clinical manifestations were nonspecific, a positive family history was not considered, or an incorrect diagnosis had been made. The presenters made pleas for better education of professionals and a higher index of suspicion about FXS.

Psychologists proposed testing for patients with MR, using the Stanford Binet for IQ and the Vineland for Adaptive Behavior as a first stage, and areas of strength and weaknesses and more specific functions in second stage tests. Comparing cognitive and behavioral abilities in children with FXS and with non-FXS autism, IQ scores in FXS show a significant decline with time, whereas individuals with autism manifest relatively no change in cognitive levels. In contrast, both groups show significant longitudinal decreases in adaptive behavior. In another presentation, therapy of ADHD symptoms in 11 children with FXS, some showed an increase in performance on executive function tasks using Adderall. Other sessions on FXS were on population screening and the molecular basis of FXS. [1]

COMMENT. The frequency of missed diagnosis in cases of FXS is of interest. Guidelines have previously been suggested to aid the practicing physician in determining which children should have a chromosomal analysis. (see Progress in Pediatric Neurology I, PNB Publishers, 1991;ppl96-7).

An estimate of the prevalence of X-Linked MR syndromes is about 1:1000 mentally retarded males, 50% having FXS. The clinical manifestations of FXS include: mental retardation, developmental delay, speech delay, ADHD, temper tantrums, mouthing of objects, autistic behaviors, and impaired gross motor coordination. ADHD is diagnosed in 50% or more of FXS patients. Epilepsy occurs in 25%. A positive family history for mental retardation is reported in 65%, and 90% of cases have a family history of either retardation, learning disability, or hyperactivity.

Physical findings include: large ears (75%), prominent jaw and long face (70%), macrocephaly (40%), hypertelorism (40%), simian palmar creases (35%), and large testicles (17%). A chromosomal analysis for FX is most likely to be positive for FXS in young males with developmental delay (especially speech delay), a maternal family history for MR, and facial dysmorphism (especially large ears, long face, and prominent jaw). For further articles on FXS, see Progress in Pediatric Neurology II, PNB, 1994;295-299. Despite the guidelines and a high index of suspicion, particularly among boys with ADHD, I still find the selection of likely candidates for chromosome testing to be difficult, with few positives in my practice of pediatric neurology.