To present the longitudinal magnetic resonance imaging (MRI) findings of a child with Kleefstra syndrome (KS) and provide literature review of neuroimaging findings of this condition.

KS is a rare genetic condition associated with developmental delay, generalized hypotonia, distinctive facial dysmorphisms, and neuropsychiatric anomalies. KS can be caused by either submicroscopic deletions of the distal long arm of chromosome 9q or intragenic loss of function in the EHMT1 (Euchromatic Histone Methyltransferase 1) gene (MIM♯ 607001), both leading to haploinsufficiency of the EHMT1. EHMT1 might have a role in myelination; disruption of its function may lead to white matter abnormalities.

Case report with longitudinal MRI findings and review of reported neuroimaging findings in the literature based on PubMED search.

A 14-year-old girl presented with developmental delay and dysmorphism at age 18 months. Chromosomal microarray showed loss of copy in the subtelomeric region of chromosome 9q confirming the diagnosis of KS. At age 23 months, MRI showed ventriculomegaly. Seizures started at age 10 years. Follow-up MRI showed cerebrospinal fluid (CSF) dissection from the right lateral ventricle which progressed similarly to the contralateral side four years later.  To date there are 100 reports of KS, and most with limited neuroimaging data and a wide range of findings from normal anatomy to hypoplasia of cerebral structures associated with ventriculomegaly to white matter changes. However, there is only one report with longitudinal MRI findings showing reversible white matter changes in this disorder. Instead, our patient’s longitudinal MRI findings revealed progressive development of CSF dissection, which remained stable on subsequent MRIs.

CSF dissection may be one of the rare neuroimaging findings of KS. The etiology of this is unclear but may be speculated to be due to the underlying white matter abnormalities or the progressive laxity of the ventricular mesoderm.