Neuropsychological and neurophysiological features of WAGR syndrome: Detailed comprehensive evaluation of a patient with severe intellectual disability and autism spectrum disorder.

BACKGROUND: Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is a contiguous gene deletion syndrome caused by a de novo deletion including the 11p13 region. Although autism spectrum disorder (ASD) is frequently observed in patients with WAGR syndrome, few reports have comprehensively described its characteristics. We herein present the detailed neuropsychological and neurophysiological findings of a patient with WAGR syndrome complicated with severe psychomotor developmental delay and ASD. CASE PRESENTATION: The patient is presently a 6-year-old boy. Microarray analysis revealed a 7.1 Mb loss at 11p14.3-p13 and a 9.3 Mb loss at 11p13-p12, which encompassed the PAX6, WT1, and PRRG4 genes. His behavioral features were characteristic even among the ASD population: severe hypoesthesia to touch, pain, and temperature in addition to remarkable sensory seeking posing a high risk of serious accident. Sensory Profile analysis objectively identified a strong preference for sensory stimulation. Furthermore, his somatosensory evoked potential (SSEP) showed a mild delay in central conduction time, suggesting partial brain stem dysfunction-induced hypoalgesia. DISCUSSION: This first attempt to characterize sensory dysfunction using Sensory Profile and SSEP in WAGR syndrome may contribute to understanding its neuropsychological features and improve the quality of rehabilitation and socioeducational support in affected children.

Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.

Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a ß-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene.