Tarja Linnankivi

Hypochondroplasia (HCH), an autosomal dominant skeletal dysplasia caused by mutations in the FGFR3 gene, has not been commonly associated with neurological problems. Temporal lobe dysgenesis associated with epilepsy was recently described in single patients. In this retrospective study, we assessed neurological and neuroimaging aspects of 13 FGFR3 (N540K) mutation verified HCH patients in Finland. Eight patients had neurocognitive difficulties, ranging from specific learning disorder (2/13) to mild intellectual disability (5/13) or global developmental delay (1/13). Six of 13 patients had a history of seizures or epilepsy. Eight patients had undergone MRI. They all had structural abnormalities consistent with temporal lobe dysgenesis. Six patients had peritrigonal white matter reduction, and 4 had abnormally shaped lateral ventricles. We recommend a close follow‐up of development in patients with HCH and a low threshold for neuroimaging.

Diagnostic analysis of patients with developmental disorders has improved over recent years largely due to the use of microarray technology. Array methods that facilitate copy number analysis have enabled the diagnosis of up to 20% more patients with previously normal karyotyping results. A substantial number of patients remain undiagnosed, however.

Purpose: To study brain MRI findings in patients with 18q− syndrome and to correlate these findings with the results of the molecular breakpoint analysis.Materials and Methods: Brain MR images of 17 patients with 18q− syndrome were evaluated. Segregation analysis was performed with 15 microsatellite markers to determine the deletion breakpoints and whether the deletion included the myelin basic protein (MBP) gene.Results: One patient had an interstitial deletion of 18q which spared the MBP gene. He was the only one with normal brain MRI. All 16 patients with deletions including the MBP gene had abnormal white matter in MRI. The main finding was poor differentiation of gray and white matter on T2‐weighted images due to increased white matter signal intensity. In addition, measured signal intensity of the white matter was significantly increased in patients compared with controls.Conclusions: Poor differentiation of gray and white matter on T2‐weighted images is the most typical MRI finding of the 18q− syndrome. These results support the postulation that abnormal myelination in 18q− syndrome is due to haploinsufficiency at or near the MBP locus. J. Magn. Reson. Imaging 2003;18:414–419.