Cognitive performance impacted in Silver-Russell syndrome, particularly with underlying mUPD7

medwireNews: Researchers have found reduced brain volume in children with Silver-Russell Syndrome (SRS), as well as cognitive impairment that is dependent on the underlying genetic defect.

They found significantly impaired performance in seven children aged 6–16 years with maternal uniparental disomy of chromosome 7 (mUPD7) relative to 33 healthy school-age controls for IQ, Verbal Comprehension Index, Perceptional Reasoning Index, Working Memory Index and Processing Speed Index.

“These results suggest that the language, the acquired knowledge, the ability to formulate and use verbal concepts, to listen to a request, to retrieve previously learned information and to express verbally are affected in mUPD7 patients,” say Natascia Di Iorgi (IRCCS Istituto Giannina Gaslini, Genova, Italy) and study co-authors.

“In addition, the lower [Perceptional Reasoning Index] result [in] this group was compatible with difficulties in recognizing shapes and images, impairment of visuo-motor, visuo-spatial capacities, non-verbal and fluid reasoning skills.”

The children with mUPD7 had significantly worse scores than nine children with SRS caused by 11p15 ICR1 loss of methylation (11p15 LOM), who themselves had cognitive function that was, on average, no worse than that of the controls. For example, average IQ was 75.8 in the mUPD7 group, 96.7 in the 11p15 LOM group and 100.8 in the controls.

Di Iorgi and team note, however, that 66% of the cohort had intrauterine growth retardation (IUGR), 80% were born small for gestational age, 43% were born preterm and 27% had experienced hypoglycaemia, all of which they say “are related ‘per se’ to an increased risk of adverse neurological outcome”.

Six of the children with mUPD7 and seven from the 11p15 LOM group also underwent magnetic resonance imaging, as did an additional five younger or older patients from each genetic group. This revealed significantly reduced grey matter volumes in the frontal and temporal lobes and globi pallidi of all the SRS patients relative to 65 healthy age- and sex-matched controls, although total grey and white matter volumes were no different between the groups.

The study authors note research showing that brain-sparing mechanisms during IUGR can be regional and focused on preserving life, but concede that this does not explain why they found cognitive impairment in the 11p15 LOM group but not the mUPD7 group.

“These results have relevant impacts for clinical management, genetic counseling, and prognosis”, the team concludes in The Journal of Clinical Endocrinology & Metabolism.

“In these patients a cognitive evaluation is recommended prior to entering school, and a tailored educational approach would serve as an important example of precision medicine to improve patients’ cognitive function and quality of life.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

J Clin Endocrinol Metab 2019; doi:10.1210/clinem/dgz151
Martin Savage
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