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PEDIATRICS Vol. 113 No. 3 March 2004, pp. 565-573

Behavioral Differences Among Subjects With Prader-Willi Syndrome and Type I or Type II Deletion and Maternal Disomy

Merlin G. Butler, MD, PhD^*, Douglas C. Bittel, PhD^*, Nataliya Kibiryeva, MD^*, Zohreh Talebizadeh, PhD^* and Travis Thompson, PhD

^* Section of Medical Genetics and Molecular Medicine, Children’s Mercy Hospitals and Clinics and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
Institute for Child Development, University of Kansas Medical Center, Kansas City, Kansas

Objective. To determine whether phenotypic differences exist among individuals with Prader-Willi syndrome with either type I or type II deletions of chromosome 15 or maternal disomy 15 leading to a better understanding of cause and pathophysiology of this classical genetic syndrome.

Methods. We analyzed clinical, anthropometric, and behavioral data in 12 individuals (5 men, 7 women; mean age: 25.9 ± 8.8 years) with PWS and a type I (TI) deletion, 14 individuals (6 men, 8 women; mean age: 19.6 ± 6.5 years) with PWS and a type II (TII) deletion, and 21 individuals (10 men, 11 women; mean age: 23.6 ± 9.2 years) with PWS and maternal disomy 15 (UPD). The deletion type was determined by genotyping of DNA markers between proximal chromosome 15 breakpoints BP1 and BP2. TI deletions are 500 kb larger than TII deletions. Several validated psychological and behavioral tests were used to assess phenotypic characteristics of individuals with PWS representing the 3 genetic subtypes.

Results. Significant differences were found between the 2 deletion groups and those with UPD in multiple psychological and behavorial tests, but no differences were observed in other clinical or anthropometric data studied. Adaptive behavior scores were generally worse in individuals with PWS and the TI deletion, and specific obsessive-compulsive behaviors were more evident in the TI individuals compared with those with UPD. Individuals with PWS with TI deletions also had poorer reading and math skills as well as visual-motor integration.

Conclusions. Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII.

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Key Words: Prader-Willi syndrome • type I and type II deletions • maternal disomy 15 • clinical differences

Abbreviations: PWS, Prader-Willi syndrome • UPD, maternal disomy 15 • AS, Angelman syndrome • BP, breakpoint • TI, type I • TII, type II • IQ, intelligence quotient • CBC, Child Behavior Checklist • Y-BOCS, Yale-Brown Obsessive-Compulsive Scale • VMI, visual-motor integration • SIB, self-injurious behavior

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Received for publication May 12, 2003; Accepted Aug 14, 2003.

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