RT Journal Article
SR Electronic
T1 A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 660
OP 668
DO 10.1136/jmedgenet-2012-101203
VO 49
IS 10
A1 Flore Zufferey
A1 Elliott H Sherr
A1 Noam D Beckmann
A1 Ellen Hanson
A1 Anne M Maillard
A1 Loyse Hippolyte
A1 Aurélien Macé
A1 Carina Ferrari
A1 Zoltán Kutalik
A1 Joris Andrieux
A1 Elizabeth Aylward
A1 Mandy Barker
A1 Raphael Bernier
A1 Sonia Bouquillon
A1 Philippe Conus
A1 Bruno Delobel
A1 W Andrew Faucett
A1 Robin P Goin-Kochel
A1 Ellen Grant
A1 Louise Harewood
A1 Jill V Hunter
A1 Sébastien Lebon
A1 David H Ledbetter
A1 Christa Lese Martin
A1 Katrin Männik
A1 Danielle Martinet
A1 Pratik Mukherjee
A1 Melissa B Ramocki
A1 Sarah J Spence
A1 Kyle J Steinman
A1 Jennifer Tjernagel
A1 John E Spiro
A1 Alexandre Reymond
A1 Jacques S Beckmann
A1 Wendy K Chung
A1 Sébastien Jacquemont
A1 on behalf of the Simons VIP Consortium
A1 on behalf of the 16p11.2 European Consortium
YR 2012
UL http://jmg.bmj.com/content/49/10/660.abstract
AB Background The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.