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. 2015 Aug 27:10:105.
doi: 10.1186/s13023-015-0323-9.

Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations

Lindsay M Oberman  1   2 , Luigi Boccuto  3 , Lauren Cascio  4 , Sara Sarasua  5 , Walter E Kaufmann  6
Affiliations

Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations

Lindsay M Oberman et al. Orphanet J Rare Dis. .

Abstract

Background: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder associated with a terminal deletion affecting chromosome 22 (22q13) that results in the loss of function of the SHANK3 gene. SHANK3 has also been identified in gene-linkage studies to be associated with autism spectrum disorder (ASD). Diagnosis of ASD in individuals with PMS is complicated by the presence of moderate to profound global developmental delay/intellectual disability as well as other co-morbid systemic and neurological symptoms.

Methods: The current study aimed to characterize the symptoms of ASD in patients with PMS and to do a preliminary exploration of genotype-ASD phenotype correlations. We conducted a standardized interview with 40 parents/guardians of children with PMS. Further, we conducted analyses on the relationship between disruption of SHANK3 and adjacent genes on specific characteristic symptoms of ASD in PMS in small subset of the sample.

Results: The majority of PMS participants in our sample displayed persistent deficits in Social communication, but only half met diagnostic criteria under the restricted, repetitive patterns of behavior, interests, or activities domain. Furthermore, logistic regressions indicated that general developmental delay significantly contributed to the ASD diagnosis. The analyses relating the PMS genotype to the behavioral phenotype revealed additional complex relationships with contributions of genes in both deleted and preserved SHANK3 regions to the ASD phenotype and other neurobehavioral impairments.

Conclusions: There appears to be a unique behavioral phenotype associated with ASD in individuals with PMS. There also appears to be contributions of genes in both deleted and preserved SHANK3 regions to the ASD phenotype and other neurobehavioral impairments. Better characterization of the behavioral phenotype using additional standardized assessments and further analyses exploring the relationship between the PMS genotype and behavioral phenotype in a larger sample are warranted.

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Figures

Fig. 1
Fig. 1
Standard scores for the Vineland II Communication, Living Skills, Social, and Motor domains. 50th percentile in the general population is 100. Average Scores reflect mild to moderate impairments in adaptive skills in patients with PMS. Blue Bars represent the entire dataset, red bars represent the subgroup who we identified to carry SHANK3 Variants green bars represent the subgroup who were confirmed not to carry a SHANK3 Variant. Error Bars represent the Standard Error of the Mean
Fig. 2
Fig. 2
Average per question scores on the ADI-R subdomains that index the core symptoms of ASD based on the DSM5 criteria. A score of zero indicates no evidence of symptoms in that subdomain, a score of one indicates some evidence of symptoms in that subdomain, a score of two indicates definite evidence of symptoms in that subdomain. Patients in this sample display evidence of symptoms in the Social Communication domain, but relatively fewer symptoms in the Restricted and Repetitive Behavior (RRB) domain. Dashed lines indicate the mean values for the subgroup who we identified to carry SHANK3 Variants. Dotted lines indicate the mean values for the subgroup who were confirmed not to carry a SHANK3 Variant. Error Bars represent the Standard Error of the Mean
See this image and copyright information in PMC

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