Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management.

Familial hydrocephalus with normal cognition and distinctive radiological features.

Hydrocephalus is a clinically and genetically heterogeneous condition. Individuals with posterior fossa abnormalities have an increased risk of developing hydrocephalus. The Dandy-Walker malformation, Dandy-Walker variant, and mega-cisterna magna (MCM) seem to represent a continuum of developmental anomalies of the posterior fossa. Here we describe the natural clinical history and the radiological features of a family with autosomal or X-linked dominant inheritance of MCM and hydrocephalus of variable severity. The affected family members demonstrate similar structural brain abnormalities including midline cyst, colpocephaly, MCM with a large posterior fossa and minimal vermian hypoplasia. The cognitive development of the affected individuals is normal. L1CAM and FOXC1 gene involvement in the pathogenesis of the disease in this family was excluded. The rare possibility of autosomal dominant or X-linked dominant inheritance and variable penetrance and expressivity must always be considered in genetic counseling of families with hereditary hydrocephalus.