Database Of Clinical Data For Individuals With Variants In The IRF2BPL Gene (IRF2BPL)

• ClinicalTrials.gov Identifier: NCT03892798
• Recruitment Status: Recruiting
• First Posted: March 27, 2019
• Last Update Posted: August 2, 2021
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Loren Pena, Children's Hospital Medical Center, Cincinnati

Tracking Information

• First Submitted Date: January 25, 2019
• First Posted Date: March 27, 2019
• Last Update Posted Date: August 2, 2021
• Actual Study Start Date: November 27, 2018
• Estimated Primary Completion Date: December 2038 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2019)

Questionnaire [ Time Frame: Throughout study completion, with the assessment completed on average once per year. ]

The investigators will collect information regarding age at development of symptoms, age at diagnosis, method for diagnosis, specific mutations detected, additional complications with age at onset and treatment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 26, 2019)

Genotype-phenotype correlations [ Time Frame: Throughout study completion, with the assessment completed on average once per year. ]

The investigators will assess for correlations between the type of variant in the IRF2BPL gene, the location of the variant, and the clinical presentation and symptoms.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Database Of Clinical Data For Individuals With Variants In The IRF2BPL Gene
• Official Title: Database Of Clinical Data For Individuals With Variants In The IRF2BPL Gene
• Brief Summary: This protocol serves as a data collection tool for individuals with variants (missense, nonsense, frameshifts) in the IRF2BPL gene (MIM 611720), which causes Neurodevelopmental Regression, Seizures, Autism and Developmental Delay (NEDAMSS, MIM 618088) and may be involved in other neurodevelopmental presentations. This information will be analyzed to develop a better understanding of the findings and progression of symptoms in individuals with variants in the IRF2BPL gene.
• Detailed Description: Neurodevelopmental Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS) is caused by changes in the IRF2BPL gene. Variants in the gene can also lead to other neurodevelopmental presentations. Due to the limited number of cases that have been described to date, clinicians may have a limited understanding of what types of symptoms can develop in affected individuals and at what age. The purpose of the study is to gather clinical information about progression, treatments and outcomes for patients with variants in IRF2BPL. The investigators will collect information about medical history, growth, development, treatments and the results of previous genetic tests. In some cases, the investigators may also collect tissue samples. This is a non-interventional study that will expand the current understanding of the range of health concerns that can be seen in individuals with changes in the IRF2BPL gene by collecting medical information and samples from a larger group of affected individuals.
• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Other
• Target Follow-Up Duration: 20 Years

Biospecimen

Retention:   Samples With DNA

Description:

If available left-ever tissue and blood from clinical investigations may be stored in the CCHMC Biorepository for future research.

• Sampling Method: Non-Probability Sample
• Study Population: The study population will consist of children and adults who are diagnosed with NEDAMSS and have variants in the IRF2BPL gene.

Condition

• Autism Spectrum Disorder
• Movement Disorders
• Seizures
• Dystonia
• NEDAMSS

Intervention

Other: No interventions are planned

No interventions are planned

• Study Groups/Cohorts: Not Provided

Publications *

• Marcogliese PC, Shashi V, Spillmann RC, Stong N, Rosenfeld JA, Koenig MK, Martinez-Agosto JA, Herzog M, Chen AH, Dickson PI, Lin HJ, Vera MU, Salamon N, Graham JM Jr, Ortiz D, Infante E, Steyaert W, Dermaut B, Poppe B, Chung HL, Zuo Z, Lee PT, Kanca O, Xia F, Yang Y, Smith EC, Jasien J, Kansagra S, Spiridigliozzi G, El-Dairi M, Lark R, Riley K, Koeberl DD, Golden-Grant K; Program for Undiagnosed Diseases (UD-PrOZA); Undiagnosed Diseases Network; Yamamoto S, Wangler MF, Mirzaa G, Hemelsoet D, Lee B, Nelson SF, Goldstein DB, Bellen HJ, Pena LDM. IRF2BPL Is Associated with Neurological Phenotypes. Am J Hum Genet. 2018 Sep 6;103(3):456. doi: 10.1016/j.ajhg.2018.08.010. No abstract available.
• Tran Mau-Them F, Guibaud L, Duplomb L, Keren B, Lindstrom K, Marey I, Mochel F, van den Boogaard MJ, Oegema R, Nava C, Masurel A, Jouan T, Jansen FE, Au M, Chen AH, Cho M, Duffourd Y, Lozier E, Konovalov F, Sharkov A, Korostelev S, Urteaga B, Dickson P, Vera M, Martinez-Agosto JA, Begemann A, Zweier M, Schmitt-Mechelke T, Rauch A, Philippe C, van Gassen K, Nelson S, Graham JM Jr, Friedman J, Faivre L, Lin HJ, Thauvin-Robinet C, Vitobello A. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet Med. 2019 Apr;21(4):1008-1014. doi: 10.1038/s41436-018-0143-0. Epub 2018 Aug 31.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 26, 2019): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2039
• Estimated Primary Completion Date: December 2038 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Living or deceased individuals with variants in the IRF2BPL gene

Exclusion Criteria:

• None

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Months to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Loren Pena, MD, PhD; 513-636-4760; loren.pena@cchmc.org

Contact: Vandana Shashi, MD; 919-684-2036; vandana.shashi@duke.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03892798
• Other Study ID Numbers: 2018-6357
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Loren Pena, Children's Hospital Medical Center, Cincinnati
• Original Responsible Party: Same as current
• Current Study Sponsor: Children's Hospital Medical Center, Cincinnati
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Loren Pena, MD, PhD; Children's Hospital Medical Center, Cincinnati

• PRS Account: Children's Hospital Medical Center, Cincinnati
• Verification Date: July 2021