Clinical and Neurophysiological Phenotype of Phelan Mcdermid Syndrome: Communication Disorder or Autism?

Poster Presentation
Friday, May 11, 2018: 5:30 PM-7:00 PM
Hall Grote Zaal (de Doelen ICC Rotterdam)
L. Ponson1, M. Gomot2, R. Blanc3,4, C. Barthelemy5, S. Roux6, A. Munnich7, N. Hernandez8, E. Houy-Durand9, S. Romana10, V. Malan10 and F. Bonnet-Brilhault11, (1)CHRU Tours, Tours, France, (2)UMR 930 Inserm-Universite Francois Rabelais Tours, Tours Cedex 09, France, (3)Université Paris Descartes, Boulogne Billancourt, France, (4)psychology, Université Paris Descartes, Boulogne Billancourt, France, (5)UMR 930 Inserm-Universite Francois Rabelais Tours, Tours, France, (6)Université François-Rabelais de Tours, UMR INSERM U930, Tours, France, (7)Service d'Histologie-Embryologie et Cytogénétique, Université Paris Descartes Paris France, Paris, France, (8)Université François Rabelais de Tours, Tours, France, (9)UMR930 Inserm, Université François-Rabelais de Tours, Tours, France, (10)Université Paris Descartes Paris France, Paris, France, (11)UMR 1253, iBrain, Université de Tours, Inserm, Tours, France

The 22q13 deletion syndrome also known as Phelan-McDermid syndrome is a neurodevelopmental disorder characterized by hypotonia, global developmental delay with intellectual disability, severely delayed or absent speech and minor dysmorphia. Behavioral symptoms of Autism spectrum disorder (ASD) are reported for half of patients carrying this deletion of various size and encompassing SHANK 3 gene. SHANK3 haploinsuffisancy has been proposed as one of the more common monogenic causes of ASD and used for monogenic mouse models of autism spectrum disorders. However extensive clinical characterization of patients carrying this deletion is lacking whereas it is essential to understand genotype-phenotype correlation and to define an appropriate therapeutic program.


The aim of our study was to better characterize autistic behaviours in PD syndrome and to test whether they are related to atypical information process reported in autism by combining genomic, behavioural dimensional and neurophysiological explorations.


Eighteen patients (8 males, mean age 12,7 years SD=9,2) with known 22q13 terminal deletions were fully explored with behavioural, language and cognitive standardized assessments. Neurophysiological indices previously reported to be altered in autism (ie Eye tracking in a social/non-social task, and Mismatch auditory evoked potentials) were also recorded. In parallel with these clinical and neurophysiological investigations carried out in the child psychiatry department of the CHU of Tours, cytogenetic analyses were carried out in the Cytogenetics Department of the Necker Enfants-Malades Hospital in Paris. All participants or the children participants' parents gave written informed consent according to institutional guidelines. The experiment was approved by an ethical committee.


Autism spectrum disorder clinical features reported by parents through ADI-R (Autism Diagnosis Interview based on the 4-5 years old period) found exceeding cut-off scores in 56% of cases. Using ADOS-2 (Autism Diagnosis Observation Schedule for current period), 50% met ASD clinical criteria exceeding cut-off scores. However only 39% remain positive when both ADOS-2 and ADI-R were required. All the patients had intellectual disability (mild, severe, profound) and language disability. Deletion size was significantly correlated with expressive and receptive language disorder but not with ADI-R nor ADOS or Developmental Quotient scores. Considering neurophysiological recordings, lack of pupil dilation for human faces which is typically described in ASD was not observed in these patients. Atypical shortened latency of Mismatch Negativity response previously reported in ASD was not observed either whereas N250 pattern, related to language, was affected.

Conclusions: The main genotype-phenotype correlation in 22q13 syndrome was related to language disorder. Combined with cognitive deficits this may lead to behavioral autistic symptoms but with different neurophysiological networks compared to typical autism. Our results should have consequences for research on animal models for which it should be verified that they involve the targeted networks. They also recall the need of precise stratification of patients in autism failing which the spectrum obscures the underlying pathophysiology. Finally, these results highlight the indication for early speech therapy rather than intensive autism program to treat patients with Phelan McDermid syndrome.

See more of: Genetics
See more of: Genetics