Longitudinal Study of Neurogenetic Disorders

NCT03492060 | Recruiting

• 1 other identifier: AAAR7203
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to analyze patterns in individuals with hnRNP (and other) genetic variants, including their neurological comorbidities, other medical problems and any treatment. The investigators will maintain an ongoing database of medical data that is otherwise being collected for routine medical care. The investigators will also collect data prospectively in the form of questionnaires, neuropsychological assessments, motor assessments, and electroencephalography to examine the landscape of deleterious variants in these genes.

Conditions

Neurodevelopmental Disorders; Intellectual Disability; Developmental Delay; Autism Spectrum Disorder; Seizures; Hypertonia, Muscle; Hypotonia

Keywords

Gene Variant; HNRNPA1; HNRNPA2; HNRNPB1; HNRNPC1; HNRNPC2; HNRNPD; HNRNPE1; HNRNPE2; HNRNPE3; HNRNPE4; HNRNPG; HNRNPH1; HNRNPH2; HNRNPI; HNRNPK; HNRNPL; HNRNPM; HNRNPP; HNRNPQ1; HNRNPQ2; HNRNPQ3; HNRNPR; HNRNPU

Outcome Measures

Primary Outcomes (18)

• Medical abnormalities associated with genetic variants

  Gene variants are known to result in a variety of clinical phenotypes. The study is intended to accrue data from medical records that document the range of neurological phenotypes and explore their incidence and frequency across genetic cohorts.

  5 years

• Education-based impairments associated with genetic variants

  The study seeks to collect records from the schools attended by participants; including: Individualized Education Programs (IEPs) and school records. We intend to use these records, in tandem with medical records, to explore meaningful statistical and clinical relationships in the phenotypes expressed by the population of the study.

  5 years

• Repetitive Behavior

  Correlations (r) between mutant allele (obtained from retrospective data) and repetitive behavior (measured by the Repetitive Behavior Scale - Revised; RBS-R)

  5 years

• Sleep Habits

  Correlations (r) between mutant allele (obtained from retrospective data) and sleep habits (measured by The Children's Sleep Habits Questionnaire; CSHQ)

  5 years

• Sensory Issues

  Correlations (r) between mutant allele (obtained from retrospective data) and sensory issues (measured by The Short Sensory Profile; SSP)

  5 years

• Social Interaction and Communication SRS-II Score

  Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Responsiveness Scale - Second Edition; SRS-II)

  5 years

• Anxiety

  Correlations (r) between mutant allele (obtained from retrospective data) and anxiety (measured by The Spence Children's Anxiety Scale - Preschool and Parent Reports; SCAS - Preschool and SCAS - P)

  5 years

• Receptive Language Skills

  Correlations (r) between mutant allele (obtained from retrospective data) and receptive language skills (measured by a 20-item music exposure questionnaire evaluating exposure on a 3-point scale: rarely, sometimes, often; and an EEG with music paradigm)

  5 years

• Executive Functioning

  Correlations (r) between mutant allele (obtained from retrospective data) and executive functioning (measured by The Behavior Rating Inventory of Executive Function - Parent Report; BRIEF-P)

  5 years

• Autism

  Correlations (r) between mutant allele (obtained from retrospective data) and autism (measured by The Childhood Autism Rating Scale; CARS)

  5 years

• Adaptive Behavior

  Correlations (r) between mutant allele (obtained from retrospective data) and adaptive behavior (measured by The Vineland Adaptive Behavior Scales, Third Edition; Vineland - 3)

  5 years

• Social Interaction and Communication SCQ Score

  Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Communication Questionnaire; SCQ)

  5 years

• Emotional Regulation

  Correlations (r) between mutant allele (obtained from retrospective data) and emotional regulation (measured by The Behavioral Assessment System for Children - Third Edition; BASC - 3)

  5 years

• Motor Performance

  Correlations (r) between mutant allele (obtained from retrospective data) and motor performance (measured by The Movement Assessment Battery for Children - Second Edition; MASC-II)

  5 years

• Function in Daily Activities, Mobility, Social and Cognitive, and Responsibility

  Correlations (r) between mutant allele (obtained from retrospective data) and functional capability in daily activities and mobility (measured by The Pediatric Evaluation of Disability Inventory Computer Adaptive Test; PEDI-CAT)

  5 years

• Functional Balance

  Correlations (r) between mutant allele (obtained from retrospective data) and functional balance and gross motor function (measured by a 14-item Pediatric Balance Scale)

  5 years

• Functional Capability and Mobility

  Correlations (r) between mutant allele (obtained from retrospective data) and functional mobility (measured by an 11-point Movement Questionnaire)

  5 years

• Coordination and Gait

  Correlations (r) between mutant allele (obtained from retrospective data) and gait (measured by a Kinematic Evaluation utilizing Solesound Pedishoe Sandals and GaitRite Walkway)

  5 years

Study Arms (2)

Variant in a hnRNP gene

Individuals with a variant in any hnRNP gene who present with neurodevelopmental abnormalities are eligible for the study.

Variant in other gene

Individuals with a confirmed variant in other genes who present with neurodevelopmental abnormalities are eligible for the study.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals who have already undergone genetic testing and carry a variant in any gene. Individuals will often present with neurological abnormalities, although the absence of symptoms is not exclusion criterion for the study. International subjects are welcome to enroll if eligibility criteria is met.

You may qualify if:

• Individuals must have had whole genome/exome sequencing and have a confirmed variant in any gene.

You may not qualify if:

• Subjects who cannot provide genetic confirmation of a predicted deleterious variant in any gene.

Sponsors & Collaborators

• Columbia University: lead
• Simons Foundation: collaborator
• New York University: collaborator
• Hackensack Meridian Health: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Related Publications (3)

• Bain JM, Cho MT, Telegrafi A, Wilson A, Brooks S, Botti C, Gowans G, Autullo LA, Krishnamurthy V, Willing MC, Toler TL, Ben-Zev B, Elpeleg O, Shen Y, Retterer K, Monaghan KG, Chung WK. Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. Am J Hum Genet. 2016 Sep 1;99(3):728-734. doi: 10.1016/j.ajhg.2016.06.028. Epub 2016 Aug 18.

  PMID: 27545675 BACKGROUND

• Bain JM, Thornburg O, Pan C, Rome-Martin D, Boyle L, Fan X, Devinsky O, Frye R, Hamp S, Keator CG, LaMarca NM, Maddocks ABR, Madruga-Garrido M, Niederhoffer KY, Novara F, Peron A, Poole-Di Salvo E, Salazar R, Skinner SA, Soares G, Goldman S, Chung WK. Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder. Neurol Genet. 2021 Jan 29;7(1):e551. doi: 10.1212/NXG.0000000000000551. eCollection 2021 Feb.

  PMID: 33728377 RESULT

• Davis TJ, Salazar R, Beenders S, Boehme A, LaMarca NM, Bain JM. A Prospective, Longitudinal Study of Caregiver-Reported Adaptive Skills and Function of Individuals with HNRNPH2-related Neurodevelopmental Disorder. Adv Neurodev Disord. 2024;8(3):445-456. doi: 10.1007/s41252-023-00346-1. Epub 2023 Aug 7.

  PMID: 39220267 DERIVED

Related Links

• Original HNRNPH2 genetic cohort website

Biospecimen

Retention: SAMPLES WITH DNA

Blood and tissue samples will be obtained through one of three ways: 1. The sample can be taken as part of routine clinical care; for example, by a referring physician, and sent to our site for storage. 2. An existing sample you may have provided for research in another study can be transferred to our site for storage. 3. The sample can be taken by the Principal Investigator of this study for research and will be stored at our site.

MeSH Terms

Conditions

Neurodevelopmental Disorders; Intellectual Disability; Learning Disabilities; Autism Spectrum Disorder; Seizures; Muscle Hypertonia; Muscle Hypotonia

Condition Hierarchy (Ancestors)

Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Communication Disorders; Child Development Disorders, Pervasive; Neuromuscular Manifestations

Study Officials

• Jennifer M. Bain, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer M. Bain, MD, PhD

CONTACT

646-426-3876; jb3634@cumc.columbia.edu

Joanna Feng

CONTACT

jlf2218@cumc.columbia.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2018
• First Posted: April 10, 2018
• Study Start: June 13, 2018
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available per request as it is accrued throughout the course of the study.
• Access Criteria: Data access requests will be reviewed by the PI and study team. Requestors will be required to sign a data access agreement.

Locations

US (1)