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Background Axonal guidance disorders are characterized by white matter tracts with an anomalous course, failure to cross the midline, or presence of anomalous white matter tracts. Diffusion tensor imaging (DTI) is a suitable noninvasive, in vivo neuroimaging tool to study axonal guidance disorders. We describe a novel disorder in a boy with compound heterozygous variants in the ROBO1 gene. Patient Description The child was referred at age 13 months because of developmental delay. At age nine years, he had severe intellectual disability and hyperactivity. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia. Brain magnetic resonance imaging with DTI revealed marked pontine hypoplasia, thinning of the anterior commissure and corpus callosum, and absence of the transverse pontine fibers. In addition, at the level of the pons the corticospinal tracts and medial lemnisci were not clearly separated from each other. Whole exome sequencing revealed compound heterozygous variants in the ROBO1 gene. Conclusion This child's neuroimaging phenotype (absence of the transverse pontine fibers and thinning of the anterior commissure and corpus callosum as shown by DTI) is suggestive of an axonal guidance disorder and supports a pathogenic role of the compound heterozygous variants in the ROBO1 gene.

The SOX5 gene encodes a transcription factor involved in the regulation of nervous system development and chondrogenesis. This article reports on two cases of 12p12.1 deletion involving SOX5 presenting with global developmental delay, intellectual disability, expressive language delay, mild motor impairment, distinct features, and multiorgan involvement. The first case involves a 32-month-old boy with de novo 53-kilobase interstitial deletion at 12p12.1, representing the smallest deletion reported, and presents with severe symptomatology. The second case is a 31-month-old girl with 3.2-megabase deletion at 12p12.2 p12.1 with severe neurodevelopmental disability and minimal organ involvement. These patients bear many of the characteristics previously reported in patients with SOX5 mutations. We propose a neurodevelopmental approach to a novel syndrome with dose- and location-sensitive SOX5 gene expression.