Clinical trial NCT00511381: Genetic Testing in Detection of Late-Onset Hearing Loss
Official title: Utility of Genetic Testing in Detection of Late-Onset Hearing Loss
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hearing Loss
Late-Onset Hearing Loss
Deafness
Keywords: Hearing Loss
Late-Onset Hearing Loss
Deafness
Lead sponsor: Pediatrix
Sponsor class: OTHER
First posted: 2007-08-03
Enrollment: 3681
Sex: ALL
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospital

Brief summary: Two major limitations of existing audiometric newborn hearing screening programs are their inability to detect forms of deafness that are not expressed at birth and the low compliance with obtaining recommended audiologic confirmation and/or follow-up. Molecular genetic tests on blood spots from all newborns will identify those at risk for the most frequent causes of late-onset hearing loss and to add these infants to the group who should receive continued audiologic monitoring.

Detailed description: Two major limitations of existing audiometric newborn hearing screening programs are their inability to detect forms of deafness that are not expressed at birth and the low compliance with obtaining recommended audiologic confirmation and/or follow-up. Molecular genetic tests on blood spots from all newborns will identify those at risk for the most frequent causes of late-onset hearing loss and to add these infants to the group who should receive continued audiologic monitoring.

The specific aims of this project are to:

* Demonstrate the utility of detecting four potentially important causes of delayed onset hearing loss by molecular tests at birth, which may be missed by current audiometric screening tests.
* Document the frequency, clinical and genetic characteristics of hearing loss associated with each condition.

Dried blood spots (DBS) on filter paper will be obtained and be used for this project with parental informed consent from 6,000 newborn infants at approximately 25 hospitals. Pediatrix Screening, a subsidiary of Pediatrix Medical Group with long experience in high throughput neonatal testing, will perform genetic testing on the samples. The four genetic and environmental forms of deafness to be studied include:

* Prenatal/congenital cytomegalovirus (CMV) infection

  -Detecting the presence of CMV viral DNA in dried blood spots.
* Connexin Deafness - GJB2 and GJB6 mutations

  - Cx26 35delG, Cx26 235delC, Cx26 167delT, Cx26 M34T, and Cx30 large deletion.(Under sublicense with Athena Diagnostics, Inc: United States Patent Numbers: 5,998,147 and 6,485,908 and patents pending)
* Pendred Syndrome - SLC26A mutations

  - L236P, 1001 +1G\>A, T416P, E384G
* Mitochondrial Mutations - T961C, T961G, G951A, 961 delT+C(n)Ins, G7444A, A7445G, A7445C.

Eligibility criteria: Inclusion Criteria:

* Documentation of informed consent
* Inborn
* Ability to do ABR (auditory brainstem response screen technology) screening test on all participants
* Age at enrollment less than 14 days or less than or equal to 336 hours (Birth date is day 0)
* Gestational age \> = 34 0/7 weeks and above. (Late preterm infants and term infants)
* No major anomalies
* Ability to obtain blood sample prior to administration of any blood product transfusion
* Subjects' parents or legal guardian willing to provide follow-up data on their child. They will need to provide a telephone contact number and address for follow-up procedures

Exclusion Criteria:

* Older than 14 days of age or 336 hours
* Receipt of a blood product prior to the ability to obtain blood sample for genetic testing (SoundGene panel)
* Any major congenital anomalies. (chromosomal abnormalities, cyanotic congenital heart disease, gastroschisis, omphalocele, diaphragmatic hernia, or other major gastrointestinal anomalies, major neurological injury or anomaly, and multiple congenital anomalies)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Topeka
country: United States
facility: Stormont-Vail HealthCare
state: Kansas
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
Study officials:
affiliation: Pediatrix
name: Gail Lim, ARNP
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatrix Screening
name: Zhili Lin, MD, PhD
role: STUDY_CHAIR
affiliation: Pediatrix
name: Reese H Clark, MD
role: STUDY_CHAIR
References: