Pilot Study of a Novel Computerized Task to Assess Spatial Learning in Children and Adolescents With Neurofibromatosis Type 1

Abstract Difficulties with visual-spatial learning are frequently observed and often considered to be the hallmark of neurocognitive impairment in neurofibromatosis type 1. The computerized Arena Maze is a virtual environment task that has been developed as a human paradigm to the Morris Water Maze, which is used to evaluate spatial learning in animal models. The authors evaluated this task as a measure of spatial learning in children with neurofibromatosis type 1 compared with their unaffected siblings. Affected children were able to learn the task and navigate the virtual environment; however, they performed more poorly on standard measures of spatial learning and spatial working memory than their siblings. The group with neurofibromatosis type 1 demonstrated decreased proficiency in earlier target trials and had more difficulty in remembering target location. This study demonstrates the potential utility of a novel virtual task to assess spatial learning deficits in children with neurofibromatosis type 1

The phenotype of recurrent 10q22q23 deletions and duplications

The genomic architecture of the 10q22q23 region is characterised by two low-copy repeats (LCRs3 and 4), and deletions in this region appear to be rare. We report the clinical and molecular characterisation of eight novel deletions and six duplications within the 10q22.3q23.3 region. Five deletions and three duplications occur between LCRs3 and 4, whereas three deletions and three duplications have unique breakpoints. Most of the individuals with the LCR3–4 deletion had developmental delay, mainly affecting speech. In addition, macrocephaly, mild facial dysmorphisms, cerebellar anomalies, cardiac defects and congenital breast aplasia were observed. For congenital breast aplasia, the NRG3 gene, known to be involved in early mammary gland development in mice, is a putative candidate gene. For cardiac defects, BMPR1A and GRID1 are putative candidate genes because of their association with cardiac structure and function. Duplications between LCRs3 and 4 are associated with variable phenotypic penetrance. Probands had speech and/or motor delays and dysmorphisms including a broad forehead, deep-set eyes, upslanting palpebral fissures, a smooth philtrum and a thin upper lip. In conclusion, duplications between LCRs3 and 4 on 10q22.3q23.2 may lead to a distinct facial appearance and delays in speech and motor development. However, the phenotypic spectrum is broad, and duplications have also been found in healthy family members of a proband. Reciprocal deletions lead to speech and language delay, mild facial dysmorphisms and, in some individuals, to cerebellar, breast developmental and cardiac defects