Cerebral white matter abnormalities associated with chromosome 18q duplication

Chromosome 18q duplications are associated with a range of phenotypes often similar to complete trisomy 18, variably including poor growth, feeding difficulties, congenital malformations and dysmorphic facial features. Although 18q duplication patients may have seizures and developmental impairment, brain MRI typically shows only variable degrees of cerebral atrophy.

We present a boy with a 52.2 Mb 18q duplication in whom brain MRI in the neonatal period showed striking white matter abnormalities, most notable in the frontal lobes. His clinical presentation was otherwise in keeping with trisomy 18, including characteristic facial features, hypotonia, cardiac malformation, rocker bottom feet, pectus excavatum, short and broad thumbs and halluces, and diabetes insipidus.

Since not previously reported in association with 18q duplication, the observation of cerebral white matter anomalies is particularly interesting. This radiologic pattern is a well-recognized feature of 18q deletion syndrome, hypothesized by many to occur due to haploinsufficiency of MBP, the gene encoding myelin basic protein. The mechanisms leading to the white matter anomalies in this patient remain unexplained.