A Natural History Study of hnRNP-related Disorders

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03492060

Collaborator

Simons Foundation (Other), New York University (Other), Hackensack Meridian Health (Other), Universitätsklinikum Hamburg-Eppendorf (Other)

1,000

Enrollment

Location

69.6

Anticipated Duration (Months)

14.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neurodevelopmental Disorders Intellectual Disability Developmental Delay Autism Spectrum Disorder Seizures Hypertonia, Muscle Hypotonia

Detailed Description

Neurodevelopmental disorders are a group of disorders in which the development of the central nervous system is disturbed. The genetic basis for many neurodevelopmental disorders has continued to expand and a recent gene called HNRNPH2 (Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2) is one such gene that is associated with a common neurodevelopmental disorder characterized by developmental delay, intellectual disability, autism and autistic features, and tone abnormalities, among other multisystem problems.

The investigators will expand the genetic cohort to include any individual with a confirmed variant in any gene presenting with neurodevelopmental abnormalities. This is non-interventional study that examines both data previously used in clinical practice and prospective data collection in the form of questionnaires and assessments. The investigators will examine patterns of initial presentation, patterns in neurological evaluations; neurological testing including brain MRI and electroencephalography, and outcomes in individuals with genetic variants.

Genes of Focus:

hnRNPA1 hnRNPA2 hnRNPB1 hnRNPB2 hnRNPC2 hnRNPD hnRNPE1 hnRNPE2 hnRNPE3 hnRNPE4 hnRNPG hnRNPH1 hnRNP H2 hnRNPI hnRNPK hnRNPL hnRNPM hnRNPP hnRNPQ1 hnRNPQ2 hnRNPQ3 hnRNPR hnRNPU

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Natural History Study of hnRNP and Other Gene-related Disorders

Actual Study Start Date :

Jun 13, 2018

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Medical abnormalities associated with genetic variants [5 years]
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.
Education-based impairments associated with genetic variants [5 years]
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.
Repetitive Behavior [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and repetitive behavior (measured by the Repetitive Behavior Scale - Revised; RBS-R)
Sleep Habits [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and sleep habits (measured by The Children's Sleep Habits Questionnaire; CSHQ)
Sensory Issues [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and sensory issues (measured by The Short Sensory Profile; SSP)
Social Interaction and Communication SRS-II Score [5 years]
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)
Anxiety [5 years]
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)
Receptive Language Skills [5 years]
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)
Executive Functioning [5 years]
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)
Autism [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and autism (measured by The Childhood Autism Rating Scale; CARS)
Adaptive Behavior [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and adaptive behavior (measured by The Vineland Adaptive Behavior Scales, Third Edition; Vineland - 3)
Social Interaction and Communication SCQ Score [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and social interaction and communication issues (measured by The Social Communication Questionnaire; SCQ)
Emotional Regulation [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and emotional regulation (measured by The Behavioral Assessment System for Children - Third Edition; BASC - 3)
Motor Performance [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and motor performance (measured by The Movement Assessment Battery for Children - Second Edition; MASC-II)
Function in Daily Activities, Mobility, Social and Cognitive, and Responsibility [5 years]
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)
Functional Balance [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and functional balance and gross motor function (measured by a 14-item Pediatric Balance Scale)
Functional Capability and Mobility [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and functional mobility (measured by an 11-point Movement Questionnaire)
Coordination and Gait [5 years]
Correlations (r) between mutant allele (obtained from retrospective data) and gait (measured by a Kinematic Evaluation utilizing Solesound Pedishoe Sandals and GaitRite Walkway)