ESPEYB17 4. Growth and Growth Factors Important for clinical practice (5 abstracts)
4.4. Cognitive profiles and brain volume are affected in patients with Silver-Russell syndrome
Patti G , De Mori L , Tortora D , Severino M , Calevo M , Russo S , Napoli F , Confalonieri L , Schiavone M , Thiabat HF , Casalini E , Morana G , Rossi A , Ramenghi LA , Maghnie M & Di Iorgi N
Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy giusypattis@gmail.com
To read the full abstract: J Clin Endocrinol Metab, April 2020, 105(4):e1478–e1488
Silver–Russell syndrome (SRS) is a rare condition associated with pre and postnatal growth retardation. The most common causes of SRS are 11p15 ICR1 loss of methylation (LOM) and maternal uniparental disomy of chromosome 7 (mUPD7). Almost all patients with SRS have a history of intrauterine growth retardation (IUGR) and may be born small for gestational age (SGA). Children with SRS show typical features, including relative macrocephaly, prominent forehead, body asymmetry, feeding difficulties and cognitive delay (1)(2). SRS patients with 11p15 LOM show high IGF1 levels suggestive of IGF1 insensitivity. IGF1 is implicated in brain development, in particular with neural proliferation and cognitive function (2)(3).
The aim of this study was to assess cognitive function and brain volume in 38 patients with clinical and genetic diagnosis of SRS. 30 of 38 patients (15 with 11p15 LOM; 15 with mUPD7) underwent cognitive assessment and 23 of these 30 had a brain MRI. The control groups were 33 children tested for cognitive profile and 65 who had brain MRI. The outcome measures were the intelligence quotient, Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), Processing Speed Index, and brain volume. Children with mUPD7 showed impaired cognitive profiles compared with both controls and 11p15 LOM children. Brain volumes at the frontal/temporal lobes and at the globi pallidi were reduced in all SRS patients.
Multiple factors other than SRS genetics may account for the cognitive deficit in patients with SRS, including intrauterine undernutrition, preterm birth, perinatal morbidity and neonatal hypoglycemia. MRI did not show any neuroanatomical abnormalities but gray matter volumes in temporal lobes and globi pallidi were reduced in SRS children, suggesting the brain sparing phenomenon may be regional and may play a role in neurological damage rather than protecting brain development. These findings need to be confirmed in larger SRS populations, in SRS patients with more homogenous characteristics at birth, and using more specific study designs (e.g. focused on patients with IGF2 gene deletions).
References:
1. Wakeling EL, Brioude F, Lokulo-Sodipe O, O’Connell SM, Salem J, Bliek J, et al. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13(2):105–24.
2. Lane C, Robinson L, Freeth M. Autistic traits and cognitive abilities associated with two molecular causes of Silver-Russell syndrome. J Abnorm Psychol. 2020 Apr;129(3):312–319.
3. Webb EA, O’Reilly MA, Clayden JD, et al. Effect of growth hormone deficiency on brain structure, motor function and cognition. Brain. 2012;135(Pt 1):216–227.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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