Genetic Causes of Growth Disorders

NCT02311322 | Terminated

• 2 other identifiers: 15002215-CH-0022
• Study Type: observational
• Target: 334
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Some growth disorders are caused by a change in genes. Genes are the instructions the body uses to function. Changes in genes often cause them not to work correctly. Researchers want to use a new technology called exome sequencing, to look at many genes at once. This is done by looking at DNA from blood or saliva in a lab. This method may help find the cause of disorders that researchers haven t been able to find using past methods. Objectives: \- To better understand genetic causes of growth disorders. Eligibility: \- Children and adults with growth disorders and their family members. Design:

• Participants will give a small sample of blood and/or saliva.
• Researchers will purify DNA from the sample. They will perform exome sequencing and other tests to look for changes in genes. Some participants may receive limited or no genetic tests. Researchers will let them know if exome sequencing is performed.
• Participants may have a medical history, physical exam, and lab tests. They may have x-rays or ultrasound tests to study the disorder in their family.
• Some participants may be recommended for a specific genetic test from a commercial lab. They may have to pay for that test.
• Participants will be told about test results that relate to the growth disorder. This may happen up to years after the testing. They may have to give another blood and/or saliva sample.
• Some participants may get results about other health conditions. This will only happen if the information would help the person or their family protect their health. They may have to give another blood and/or saliva sample.

Conditions

Short Stature; Growth Disorder; Syndromic Growth Disorder; Tall Stature

Keywords

Growth Disorder; Growth; Exome Sequencing

Outcome Measures

Primary Outcomes (1)

• SNP array and whole exome sequencing data

  identification of the causal variant

  1-5 years

Study Arms (2)

Children with growth disorders

Children with growth disorders

Family members of subjects with growth disorders

Family members of subjects with growth disorders

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

subjects with growth disorders

You may qualify if:

• If a subject meets any one of these criteria, he/she will potentially be eligible to participate:
• Short stature (height less than - 2 SDS), either currently or previously - or
• Tall stature (height greater than + 2 SDS) or
• Bone age delay (greater than 3 years) or
• Bone age advancement (\>1.5 years) or
• Predicted adult height \< - 2SD
• Predicted adult height - mid-parental height \< -2SDS or \> 2SDS
• Growth disorder that was treated promptly, thus maintaining the child s height within the normal range, e.g. a subject with congenital growth hormone deficiency or multiple pituitary hormone deficiency of unknown genetic etiology who received growth hormone treatment beginning in early life or
• Family member of subjects who meet any of the above criteria
• Subjects have a current height at a low normal percentile but has short adult height prediction based on bone age (\> 5 inches shorter than mid-parent height)
• Any subject who has more than one of the above criteria and elevated DHEA-S concentration for age
• In addition, subjects are only eligible, if, the pedigree suggests a monogenic inheritance, and, in the judgement of the investigators, there is a reasonable likelihood of identifying a novel gene responsible for the condition.
• Investigators may recruit study subjects through The Genomic Ascertainment Cohort (TGAC) to identify specific subjects with sequence variants in genes of interest associated with growth disorders to investigate the phenotype spectrum, regardless of the above criteria.
• Investigators may recruit study additional subjects through the NIDDK repository to identify specific subjects with sequence variants in genes of interest associated with growth disorders to investigate the phenotype spectrum, regardless of the above criteria. Investigators may first identify subjects with height \< 3rd% from these cohorts, request their DNA samples and sequence their DNA to identify a variant in a gene of interest.
• If subjects have abnormal bone age x-ray findings, investigators may use the findings as a maker for chondrodysplasia and study subjects with the findings. To recruit subjects, bone age x-rays obtained under teaching protocol (00-CH-0180 and 16-CH-0113) may be reviewed. If the subjects with abnormal findings are still followed by NIH, this study will be introduced to the patient and family. However, if subjects had been discharged from NIH care, they will not be re-contacted but their data may be still included in the prevalence of the abnormal finding. If collaborators wish to review their bone age x-rays obtained from their patients with short stature to identify the eligible subjects, they will obtain approval from their IRB. If some subjects are identified and the family agrees to participate, then collaborators refer them to our research team.

You may not qualify if:

• A non-genetic disorder or condition, either congenital or acquired, that explains the growth abnormality, for example, pituitary injury, chronic thyroiditis, whole body irradiation, or celiac disease.
• In the opinion of the investigators, there is an established diagnosis of a genetic disorder or condition that explains the growth abnormality and for which the molecular genetic etiology has already been identified, for example, SHOX deficiency, hypochondroplasia, or Noonan syndrome.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Jee YH, Gangat M, Yeliosof O, Temnycky AG, Vanapruks S, Whalen P, Gourgari E, Bleach C, Yu CH, Marshall I, Yanovski JA, Link K, Ten S, Baron J, Radovick S. Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic. Front Genet. 2021 Aug 11;12:697549. doi: 10.3389/fgene.2021.697549. eCollection 2021.

  PMID: 34456972 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood, saliva, DNA extracted from whole blood or saliva, plasma, serum, urine, skin biopsy, hair follicles

MeSH Terms

Conditions

Dwarfism; Growth Disorders

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Youn H Jee, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 8, 2014
• Study Start: December 2, 2014
• Primary Completion: March 14, 2023
• Study Completion: March 14, 2023
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)