Clinical trial NCT03492060: Longitudinal Study of Neurogenetic Disorders
Official title: Neurogenetic Disorders: A Longitudinal Study on Natural History and Intervention Strategies
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Simons Foundation
name: New York University
name: Hackensack Meridian Health
name: Universitätsklinikum Hamburg-Eppendorf
First posted: 2018-04-10
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Medical abnormalities associated with genetic variants
timeFrame: 5 years
measure: Education-based impairments associated with genetic variants
timeFrame: 5 years
measure: Repetitive Behavior
timeFrame: 5 years
measure: Sleep Habits
timeFrame: 5 years
measure: Sensory Issues
timeFrame: 5 years
measure: Social Interaction and Communication SRS-II Score
timeFrame: 5 years
measure: Anxiety
timeFrame: 5 years
measure: Receptive Language Skills
timeFrame: 5 years
measure: Executive Functioning
timeFrame: 5 years
measure: Autism
timeFrame: 5 years
measure: Adaptive Behavior
timeFrame: 5 years
measure: Social Interaction and Communication SCQ Score
timeFrame: 5 years
measure: Emotional Regulation
timeFrame: 5 years
measure: Motor Performance
timeFrame: 5 years
measure: Function in Daily Activities, Mobility, Social and Cognitive, and Responsibility
timeFrame: 5 years
measure: Functional Balance
timeFrame: 5 years
measure: Functional Capability and Mobility
timeFrame: 5 years
measure: Coordination and Gait
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Jennifer M. Bain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.