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Open Access 01-12-2013 | Research

Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome

Authors: Sylvie Tordjman, George M Anderson, David Cohen, Solenn Kermarrec, Michèle Carlier, Yvan Touitou, Pascale Saugier-Veber, Céline Lagneaux, Claire Chevreuil, Alain Verloes

Published in: Molecular Autism | Issue 1/2013

Abstract

Background

Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene–dosage effects on language development at 7q11.23 have been hypothesized.

Methods

Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined.

Results

The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production.

Conclusions

Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype–phenotype correlations, possible gene–environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism.

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Title: Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome
Authors: Sylvie Tordjman
George M Anderson
David Cohen
Solenn Kermarrec
Michèle Carlier
Yvan Touitou
Pascale Saugier-Veber
Céline Lagneaux
Claire Chevreuil
Alain Verloes
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Molecular Autism / Issue 1/2013
Electronic ISSN: 2040-2392
DOI: https://doi.org/10.1186/2040-2392-4-29

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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