An observational study in Short Stature, Growth Disorder and Syndromic Growth Disorder, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Terminated at 1 site in United States. Per ClinicalTrials.gov, last updated 2023-03-16.
Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Observational
Background:
Objectives:
Eligibility:
Design:
Children often present to pediatricians and pediatric endocrinologists because of abnormal body growth, including both childhood growth failure and, less commonly, overgrowth. Sometimes the cause is evident, for example, growth hormone deficiency for growth failure and growth hormone excess for overgrowth. In other children, the etiology remains unknown despite extensive evaluation, resulting in the unhelpful diagnosis of severe idiopathic short stature or tall stature. These conditions are quite heterogeneous, including children with isolated growth disorders and others who also have other abnormalities such as developmental delay or a constellation of congenital anomalies (syndromic growth disorders). Some cases of severe growth disorders have a polygenic inheritance while others appear to be inherited as a monogenic trait - recessive, dominant or X-linked. Because of recent advances in DNA sequencing technology, it is now feasible to sequence the exome (portion of the genome that encodes gene exons) in families with monogenic disorders and thereby determine the underlying molecular etiology.
We therefore propose a study to identify novel genetic causes of idiopathic growth disorders using whole-exome sequencing. The primary goal of this study is to identify novel causes of childhood growth disorders in order to improve clinical diagnosis, to provide a more precise characterization of associated medical problems, prognosis, and response to treatment based on etiology, and to gain new insights into the regulation of human growth, which may eventually lead to new therapeutic approaches.
Subjects will include children and adults with a clearly recognizable phenotype that includes either short stature or tall stature and a pedigree that strongly suggests a monogenic inheritance. Both syndromic and non-syndromic growth disorders and both proportionate and disproportionate growth disorders will be included. Affected and unaffected family members (who have informative meiotic inheritance relationships to the proband or index case) will also be studied because of their importance for this genetic approach. The phenotype will be characterized by medical history, physical exam, body measurements, and laboratory evaluation. Blood and saliva samples will be collected for whole-exome sequencing and single nucleotide polymorphism (SNP) array analysis. Candidate sequence variants will typically be verified by Sanger sequencing.
99 studies on the registry are indexed under Dwarfism; 12 are open to participants now.
This study's enrollment of 334 is above the median of 60 across 30 observational studies indexed under Dwarfism.
Browse Dwarfism studies →Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 422 studies on the registry; 24 are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 11 (79%) have results posted.
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subjects with growth disorders
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
If a subject meets any one of these criteria, he/she will potentially be eligible to participate:
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.
EXCLUSION CRITERIA:
Children with growth disorders
Family members of subjects with growth disorders
SNP array and whole exome sequencing data
identification of the causal variant
Time frame: 1-5 years
Plan to share: No
Ran from Dec 2014 to primary completion in Mar 2023, 99 months.
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This study is terminated, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.
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