Background: Patients with the karyotypic finding of a terminal deletion in the long arm of chromosome 18 (18q- syndrome) commonly display cerebral dysmyelination and developmental delay. To our knowledge, all reported cases characterized by molecular analysis who had no mental retardation as confirmed by neuropsychological testing had a chromosomal breakpoint within the two most distal bands, 18q22 or 18q23, leading to a deletion of 16 Mb or less.
Aims of the study: It was the aim of this study to improve the karyotype-phenotype correlation in 18q- syndrome by thoroughly analyzing the deletion size and the mental and radiologic status in a 23-year-old woman with a terminal 18q deletion. We performed cytogenetic and molecular cytogenetic analysis, brain MRI, and extended neuropsychological testing.
Results: Molecular karyotyping revealed a 17 Mb deletion of terminal 18q with a breakpoint in 18q21.33 and no evidence for mosaicism. While brain MRI demonstrated severe global dysmyelination, the patient showed a neuropsychological pattern that allowed for normal psychosocial and job achievement. After delayed development in childhood, the patient caught up during puberty and showed normal verbal intelligence and skills at 23 years. However, visual, visual-spatial, visual-constructional, and executive functions were found to be severely impaired.
Conclusion: Here, we present a patient with one of the largest terminal 18q deletions reported in an individual without obvious mental retardation. Our analysis extends the phenotypic spectrum for individuals with breakpoints in 18q21.33. In addition, this study highlights the fact that severe global dysmyelination may not be associated with general cognitive deficits.