COGNITIVE AND BEHAVIORAL CHARACTERIZATION OF THE POTOCKI-LUPSKI SYNDROME

Background: Potocki-Lupski Syndrome (PTLS; duplication 17p11.2) the homologous recombination reciprocal of the Smith-Magenis (SMS) microdeletion, is a recently recognized multiple congenital anomalies and mental retardation syndrome. Many patients have escaped ascertainment when assessed by routine cytogenetic methods.  It was hypothesized that the phenotype of PTLS would be milder than SMS as genomic duplication is generally better tolerated than deletion; mild to borderline intellectual disability and hyperactive and inattentive behavioral difficulties were anticipated. The availability of targeted array-based comparative genomic hybridization in clinical diagnostic laboratories has led to a greater sensitivity in diagnosis.

Objectives: To further characterize PTLS and to aid in clinical diagnosis, parent counseling and patient management.

Methods: Fifteen patients participated in a clinical protocol that included developmental and cognitive profiles, psychiatric assessment, and extensive medical evaluations.  Assessment tools included the Mullen Scales of Early Learning or Stanford-Binet Intelligence Scales and Leiter International Performance Scales; Vineland Adaptive Behavior Scales; Behavioral Rating Inventory of Executive Functions; Behavior Assessment System for Children; Aberrant Behavior Checklist, and Short Sensory Profile; the ADI-R and ADOS-G were added after the first seven evaluations.  Cytogenetic and molecular analyses were performed on all patients to establish genotype.

Results: The majority of patients (12/15) presented with intellectual disability in the moderate range of impairment and autistic symptoms; unexpectedly, two-thirds (10/15) met strict diagnostic criteria for autism or pervasive developmental disorder, NOS.  The most common medical clinical features in these patients included hypotonia, failure to thrive in infancy, obstructive and central sleep apnea, EEG abnormalities, and cardiovascular anomalies.

Conclusions: Although unanticipated, PTLS appears to be very highly associated with autistic spectrum disorders.  Continued assessment of patients will allow for clarification of this association and may contribute to our knowledge regarding the etiology of the pervasive developmental disorders.