Silver-Russell syndrome (SRS) is an epigenetic disorder characterized by severe intrauterine and postnatal growth retardation and typical dysmorphic features. The most common genetic abnormalities are 11p15 ICR1 loss of methylation, (11p15 LOM) and maternal uniparental disomy of chromosome 7 (mUPD7). There is little information on cognitive development in SRS patients and no neuroradiological studies are available so far. Global developmental delay and requirement for speech therapy have been reported in a few cases. It is known that IGF1/IGF2 axis, involved in the pathogenesis of SRS, plays a role in normal brain growth but little is known of the effect of SRS underlying molecular abnormalities on brain structure. We investigated a cohort of SRS children using cognitive assessment in conjunction with volumetric analysis and diffusion tensor imaging and compared the imaging findings with those of a cohort of controls. Aims: 1) Cognitive findings 2) Neuroanatomical features 3) to correlate genotype and phenotype..
Method: Neuropsychological assessments were performed in 31 patients (15 with UPD7, 15 with 11p15 LOM and 1 with cr11 duplication) followed in a single University Hospital center between 2015-2018. Brain MRI studies were performed on a 3Tesla scanner in SRS patients and in a group of 31 age-matched controls with normal brain MRI. The 3D-T1 weighted sequence was included in the scan protocol for all subjects. A Voxel-based morphometry analysis was performed on the 3D-T1-weighted sequences.
Results: The mean overall intelligence quotient (IQ) score was 86,5 ± 17 SD. Median Working Memory Index (WMI) and Processing Speed Index (PSI) were 91,3±18 SD and 93.2±19.3 SD without significant difference between the two groups. IQ, Verbal comprehension Index (VCI), Perceptual Reasoning Index (PRI) were significantly higher in 11p15LOM group than in UPD7 group at the age of 6-17 years (P= 0,01). The single patient with 11cr duplication showed a cognitive delay; 59,3% of the subjects showed signs of attention deficit/hyperactivity disorder and 18,18% had learning difficulties. VBM analysis showed lower brain volume in SRS patients than controls at level of brain frontal poles (median 2.556±0.401 SD cm3 and 2.989±0.409 cm3, respectively; P<.001) and temporal poles (median 7.434±1.354 SD cm3 and 8.304±1.186 cm3, respectively; P<.001). The intrapatient analysis revealed a significant association between the volume of mesial temporal lobes and the WMI (P=.002). No significant differences in brain volumes were observed between UPD7 and 11p15 groups.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology