A brother and sister with intellectual disability and characteristic neuroimaging findings

Leukoencephalopathy with brain calcifications and cysts (LCC) is a genetic white matter disorder, which involves the brain small blood vessels. In the absence of extra-neurological symptoms, LCC has a pathognomonic radiological phenotype. Recently, biallelic mutations in the SNORD118 gene, which is a non-protein coding gene, were discovered to cause LCC. We present here two siblings with developmental delay and a typical MRI pattern, who were diagnosed with LCC. The mutations in the SNORD118 gene were initially missed with whole exome sequencing (WES), but recognition of the MRI patterns of both children raised the suspicion of LCC and led to a genetically proven diagnosis after re-evaluation of the WES data.