Neuropsychiatric features of <scp>Prader–Willi</scp> syndrome

Shelkowitz, Emily; Gantz, Marie G.; Ridenour, Ty; Scheimann, Ann O.; Strong, Theresa V.; Bohonowych, Jessica; Duis, Jessica

doi:10.1002/ajmg.a.62662

Cited by 14 publications

(9 citation statements)

References 22 publications

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“…As in other developmental disorders, these findings highlight the detrimental association between maladaptive behaviors and the performance of skills required for personal or social self-sufficiency [20,54]. Genetic subtype differences in Profile factors and Red Flag items are consistent with previous work showing increased vulnerability to psychosis in people with mUPD, with or without a depressive component [55]. Relative to participants with paternal deletions, those with mUPD or Imprinting Deficits had higher scores on the Depressed, Anxious and Repetitive Questioning, Speech factors.…”

Section: Discussionsupporting

confidence: 87%

The Prader-Willi syndrome Profile: validation of a new measure of behavioral and emotional problems in Prader-Willi syndrome

Dykens,

Roof,

Hunt-Hawkins

2024

Orphanet J Rare Dis

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Background Prader-Willi syndrome (PWS) is a rare, neurodevelopmental disorder caused by the lack of expression of paternally imprinted genes on chromosome 15q11-13. PWS features a complex behavioral phenotype, including hyperphagia, anxiety, compulsivity, rigidity, repetitive speech, temper outbursts, aggressivity, and skin-picking. Questionnaires exist for measuring hyperphagia, but not for the aggregation of other problems that are distinctive to PWS. A PWS-specific tool is needed for phenotypic research, and to help evaluate treatment efficacy in future clinical trials aimed at attenuating PWS’s hyperphagia and related problems. In this 4-phase study, we leveraged our expertise in PWS with feedback from families and specialists to validate the PWS Profile, a novel, informant-based measure of behavioral and emotional problems in this syndrome. Results The authors developed a bank of 73 items that tapped both common and less frequent but clinically significant problems in PWS (Phase 1). An iterative feedback process with families and stakeholders was used to ensure content and construct validity (Phase 2). After adding, omitting, or revising items, in Phase 3, we pilot tested the measure in 112 participants. Results were reviewed by an international team of PWS specialists and revised again (Phase 3). The final, 57-item Profile was then administered to 761 participants (Phase 4). Principal component factor analyses (n = 873) revealed eight conceptually meaningful factors, accounting for 60.52% of test variance, and were readily interpretated as: Rigidity, Insistence; Aggressive Behaviors; Repetitive Questioning, Speech; Compulsive Behaviors; Depression, Anxiety; Hoarding; Negative Distorted Thinking; and Magical Distorted Thinking. Factors were internally consistent and showed good test-retest reliability and convergent validity with existent measures of behavioral problems. Profile factors were not related to IQ, BMI, or parental SES. Three Profile factors differed across PWS genetic subtypes. Age and gender differences were found in only one Profile factor, Hoarding. Conclusions The PWS Profile is a valid, psychometrically-sound questionnaire that already has shown responsivity to treatment in a previous clinical trial. The Profile can extend the reach of future clinical trials by evaluating the impact of novel agents not only on hyperphagia, but also on the emotional and behavioral problems that characterize PWS.

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Section: Discussionsupporting

confidence: 87%

The Prader-Willi syndrome Profile: validation of a new measure of behavioral and emotional problems in Prader-Willi syndrome

Dykens,

Roof,

Hunt-Hawkins

2024

Orphanet J Rare Dis

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“…Similarly, the research goal of the Global PWS Registry was to collect health-related data to better characterise and study the natural history of this disorder [ 28 ]. Research output stemming from the Global PWS Registry on issues such as weight problems, caregiver burden, suicidality, neuropsychiatric features, thrombosis risk and strabismus in PWS has been published, in the form of either retrospective studies from clinical and patient data collected via surveys (the largest of which featured data from 908 individuals) or prospective, observational studies recruiting individuals from the registry [ 30 , 31 , 32 , 33 , 34 , 35 ]. Such research output has been supported by funding from the Foundation for Prader–Willi Research [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Development of an International Database for a Rare Genetic Disorder: The MECP2 Duplication Database (MDBase)

Downs

Baynam

et al. 2022

Children

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The natural history of MECP2 duplication syndrome (MDS), a rare X-linked neurodevelopmental disorder with an estimated birth prevalence of 1/150,000 live births, is poorly understood due to a lack of clinical data collected for research. Such information is critical to the understanding of disease progression, therapeutic endpoints and outcome measures for clinical trials, as well as the development of therapies and orphan products. This clinical information can be systematically collected from caregivers through data collation efforts—yet, no such database has existed for MDS before now. Here, in this methodological study, we document the development, launch and management of the international MECP2 Duplication Database (MDBase). The MDBase consists of an extensive family questionnaire that collects information on general medical history, system-specific health problems, medication and hospitalisation records, developmental milestones and function, and quality of life (for individuals with MDS, and their caregivers). Launched in 2020, in its first two years of operation the MDBase has collected clinical data from 154 individuals from 26 countries—the largest sample size to date. The success of this methodology for the establishment and operation of the MDBase may provide insight and aid in the development of databases for other rare neurodevelopmental disorders.

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“…showing increased vulnerability to psychosis in people with mUPD, with or without a depressive component [55]. Relative to participants with paternal deletions, those with mUPD or Imprinting De cits had higher scores on the Depressed, Anxious and Repetitive Questioning, Speech factors.…”

Section: Genetic Subtype Differences In Pro Le Factors and Red Flag I...mentioning

confidence: 91%

The Prader-Willi syndrome Profile: Validation of a New Measure of Behavioral and Emotional Problems in Prader-Willi syndrome.”

Dykens,

Roof,

Hunt-Hawkins

2023

Preprint

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Background: Prader-Willi syndrome (PWS) is a rare, neurodevelopmental disorder caused by the lack of expression of paternally imprinted genes on chromosome 15q11-13. PWS features a complex behavioral phenotype, including hyperphagia, anxiety, compulsivity, rigidity, repetitive speech, temper outbursts, aggressivity, and skin-picking. Questionnaires exist for measuring hyperphagia, but not for the aggregation of other problems that are distinctive to PWS. A PWS-specific tool is needed for phenotypic research, and to help evaluate treatment efficacy in future clinical trials aimed at attenuating PWS’s hyperphagia and related problems. In this 4-phase study, we leveraged our expertise in PWS with feedback from families and specialists to validate the PWS Profile, a novel, informant-based measure of behavioral and emotional problems in this syndrome. Results: The authors developed a bank of 73 items that tapped both common and less frequent but clinically significant problems in PWS (Phase 1). An iterative feedback process with families and stakeholders was used to ensure content and construct validity (Phase 2). After adding, omitting, or revising items, in Phase 3, we pilot tested the measure in 112 participants. Results were reviewed by an international team of PWS specialists and revised again (Phase 3). The final, 57-item Profile was then administered to 761 participants (Phase 4). Principal component factor analyses (n=873) revealed eight conceptually meaningful factors, accounting for 60.52% of test variance, and were readily interpretated as: Rigidity, Insistence; Aggressive Behaviors; Repetitive Questioning, Speech; Compulsive Behaviors; Depression, Anxiety; Hoarding; Negative Distorted Thinking; and Magical Distorted Thinking. Factors were internally consistent and showed good test-retest reliability and convergent validity with existent measures of behavioral problems. Profile factors were not related to IQ, BMI, or parental SES. Three Profile factors differed across PWS genetic subtypes. Age and gender differences were found in only one Profile factor, Hoarding. Conclusions: The PWS Profile is a valid, psychometrically-sound questionnaire that already has shown responsivity to treatment in a previous clinical trial. The Profile can extend the reach of future clinical trials by evaluating the impact of novel agents not only on hyperphagia, but also on the emotional and behavioral problems that characterize PWS.

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Neuropsychiatric features of Prader–Willi syndrome

Cited by 14 publications

References 22 publications

The Prader-Willi syndrome Profile: validation of a new measure of behavioral and emotional problems in Prader-Willi syndrome

The Prader-Willi syndrome Profile: validation of a new measure of behavioral and emotional problems in Prader-Willi syndrome

Development of an International Database for a Rare Genetic Disorder: The MECP2 Duplication Database (MDBase)

The Prader-Willi syndrome Profile: Validation of a New Measure of Behavioral and Emotional Problems in Prader-Willi syndrome.”

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