Study of Skeletal Disorders

Clinical and Laboratory Study of Rare Skeletal Disorders

Background:

There are 461 conditions that affect the bones (skeletal disorders). Many of these are not well understood and do not have any specific treatments. Researchers want to collect more data about these conditions.

Objective:

To gain more information about the causes of skeletal disorders and how they progress over time.

Eligibility:

People ages 2 months or older with known or suspected skeletal disorders or history of pregnancy affected by skeletal findings. Also, healthy family members of affected enrolled participants.

Design:

Participants can take part in the study either remotely or in person. Those who take part remotely may send in medical records, blood samples, photographs, and other materials.

Participants medical records will be reviewed. They may give blood and/or urine samples. They will give blood, saliva, or tissue samples for genetic tests. They may have genetic counseling.

Participants ages 2 years and older may have different kinds of imaging scans, such as x-rays. For these scans, they may have to lie still while machines take pictures of their bones.

Participants with skeletal disorders who come to the clinic will be examined. They may be asked to stay in the hospital for a few days to take extra tests. They may have a bone or skin biopsy.

Participants with skeletal disorders may be photographed to show the effects of their disorder and how it changes over time.

For participants with skeletal disorders, their blood or tissue samples may be used to make a special type of stem cell. These cells can be used in the laboratory to make many other types of cells. A large supply of these cells may be created for research.

Participation will last indefinitely.

Study Overview

• Status: Recruiting
• Conditions: Skeletal Disorders

Detailed Description

Study Description:

This is a clinical and laboratory study of rare skeletal disorders using a combination of both retrospective and prospective methods. This is a single site study taking place at the NIH Clinical Center with the added ability for participants to submit medical records and specimens remotely.

Objectives:

Primary Objective: To provide a protocol in which subjects with rare skeletal disorders can be evaluated and studied and to allow for the receipt of tissues and clinical specimens from individuals and investigators outside of the NIH

Secondary Objective: To perform genetic testing including genes currently known to cause skeletal disorders as well as those currently without association with skeletal disorders

Endpoints:

Primary Endpoint: To define or further define genetic etiologies of known and unknown skeletal disorders and create genotype-phenotype correlations when possible

Secondary Endpoints: To describe natural history of individual disorders if enough data is collected on a particular condition(s)

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Holly E Babcock; Phone Number: (301) 594-3391; Email: holly.babcock@nih.gov
• Study Contact Backup: Name: Carlos R Ferreira Lopez, M.D.; Phone Number: (240) 393-5441; Email: ferreiracr@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY8664111010 800-411-1222; Email: prpl@cc.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Study cohort will include individuals with known (via clinical, radiographic or molecular diagnosis) or suspected skeletal disorders, findings associated with or increasing risk for skeletal abnormalities, or history of pregnancy affected by skeletal findings.

Description

• INCLUSION CRITERIA:

Our study population will support the mission and scientific focus of the Unit on Skeletal Genomics. We will focus enrollment of subjects (and their relatives) who fall within one of the below categories:

• Individuals with a skeletal disorder that affects phosphate levels and/or metabolism
• Individuals with a skeletal disorder associated with skeletal overgrowth
• Individuals with a skeletal disorder or history of pregnancy affected by skeletal findings with an unknown molecular basis or unknown etiology

In addition to noting the above, to be eligible to participate in this study as an affected subject, an individual must meet all of the following criteria:

1. Have a known (via clinical, radiographic or molecular diagnosis) or suspected skeletal disorder, findings associated with or increasing risk for skeletal abnormalities, or history of pregnancy affected by skeletal findings
2. State willingness to comply with study procedures and availability for the duration of the study
3. Be age 2 months or older
4. Be able to understand and sign informed consent document (or availability of a parent/guardian or LAR to provide written consent)

In order to be eligible to participate in this study as an unaffected subject, an individual must meet all of the following criteria:

1. Be an unaffected family member of an affected enrolled subject
2. State willingness to comply with study procedures and availability for the duration of the study
3. Be age 2 months or older
4. Be able to understand and sign informed consent document (or availability of a parent/guardian)

EXCLUSION CRITERIA:

The below describe exclusion criteria for an individual to participate as an affected subject:

1. An individual who cannot or is unwilling to abide by the procedures of the protocol.
2. An individual deemed to not have sufficient signs of or risks for skeletal disease.
3. An individual who is pregnant.

The below describe exclusion criteria for an individual to participate as an unaffected subject:

1. An individual who cannot or is unwilling to abide by the procedures of the protocol.
2. An individual that shows signs of skeletal disease.
3. An individual who is pregnant.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
1; Subjects with rare skeletal disorders

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define or further define genetic etiologies of known and unknown skeletal disorders and create genotype-phenotype correlations when possible	To define or further define genetic etiologies of known and unknown skeletal disorders and create genotype-phenotype correlations when possible	ongoing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe Natural History	To describe natural history of individual disorders if enough data is collected on a particular condition(s)	ongoing

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Carlos R Ferreira Lopez, M.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 23, 2026
• Last Verified: May 20, 2026

More Information

Terms related to this study

• Keywords: Natural History; Bone; Skeletal Dysplasia; Short Stature; skeletal; DWARFISM
• Additional Relevant MeSH Terms: Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; Mucopolysaccharidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Dwarfism; Mucopolysaccharidosis IV
• Other Study ID Numbers: 10000213; 000213-CH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No