Three Pediatric Siblings With CADASIL.

ABSTRACT

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a congenital small vessel disease of the brain due to NOTCH3 gene mutations. Although adult-onset CADASIL is well documented, more cases are being described within the pediatric population. We describe three siblings with NOTCH3 mutations with various symptomatic presentations of early-onset CADASIL and one sibling with concurrent moyamoya syndrome. METHODS: Review of electronic medical records of identified patients. RESULTS: A 19-year-old male who has experienced behavioral dysregulation, hallucinations, and memory loss along with a hyperintense signal abnormality in his temporal lobe; his 15-year-old sister who has the mildest presentation in terms of normal imaging results but experiences severe headaches, anxiety, and depression; and the youngest sibling, a 13-year-old with first reported case of a NOTCH3 mutation associated with moyamoya syndrome and a TREX1 gene mutation of uncertain clinical significance. She had multiple strokes before age five years. CONCLUSION: Our set of siblings share many similarities with other reported pediatric cases of CADASIL, all with NOTCH3 gene mutations and with early-onset symptoms that range from abnormalities in the cognitive/behavioral/psychiatric field to neurological deficits, migraines, and strokes. Gene testing and imaging studies in symptomatic children with a family history suggestive of CADASIL might aid in early diagnosis, even though there is no effective therapy. We believe that the correlation of clinical presentations and gene mutations together with increased research into the molecular mechanisms underlying CADASIL (and related arteriopathies such as moyamoya syndrome) are critical to the eventual development of targeted therapies.