Trial record 1 of 1 for:    "Pallister-Hall syndrome"
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Phenotype and Etiology of Pallister-Hall Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier:
NCT00001404
First received: November 3, 1999
Last updated: March 14, 2014
Last verified: January 2014
  Purpose

We aim to delineate the range of severity, natural history, molecular etiology, and pathophysiology of Pallister-Hall syndrome (PHS), Greig cephalopolysyndactyly syndrome (GCPS), McKusick-Kaufman syndrome (MKS), Bardet-Biedl syndrome (BBS), Oro-facial digital syndromes (OFDs), and other overlapping phenotypes. These disorders comprise a syndrome community of overlapping manifestations and we hypothesize that this is a reflection of a common mechanistic pathway. This hypothesis be addressed by a combined clinical-molecular approach where we bring up to 50-100 patients with each disorder to the NIH clinical center for a comprehensive clinical evaluation with follow-up at a frequency appropriate to the disorder. Specimens will be collected and evaluated in the laboratory by linkage analysis, physical mapping, candidate gene characterization, mutation screening, and cell biologic studies of normal mutant proteins.


Condition
Malformations
Multiple Abnormalies
Polydactyly

Study Type: Observational
Official Title: Genetic and Clinical Studies of Congenital Anomaly Syndromes

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 1500
Study Start Date: August 1994
Detailed Description:

We aim to use the power of modern molecular genetics and clinical research to delineate the

range of severity, natural history, molecular etiology, and pathophysiology of a number of

congenital anomaly syndromes. The goal of the research is to develop a knowledge base that allows proper clinical and molecular diagnosis of patients with rare congenital anomaly

disorders. Our paradigm is the previous work we have done with Pallister-Hall syndrome (PHS) and Greig cephalopolysyndactyly syndrome (GCPS), where we have successfully used a combined clinical-molecular approach. Using this strategy, we have brought 50-100 patients or families with these disorders to the NIH clinical center (NIH CC) for a comprehensive clinical evaluation with follow-up at a frequency appropriate to the disorder. We have also clinically and/or molecularly evaluated many additional patients with atypical or non-classic presentations of PHS and GCPS and have conducted exploratory studies of other phenotypes to determine how they might fit into the more general models generated to explain PHS and GCPS. We are currently generalizing this approach to a number of disorders including talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava (TARP) syndrome. Specimens from patients participating in both the laboratory and clinical arms of the protocol will be collected and evaluated in the laboratory by linkage analysis, physical mapping, candidate gene characterization, mutation screening and targeted exome sequencing, and cell biologic studies of normal and mutant proteins.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Subjects with clinical manifestations of a congenital anomaly or craniofacial syndrome, or a single congenital anomaly that is also seen as part of a congenital anomaly syndrome will be considered eligible for participation in this protocol.

Blood will also be requested on unaffected relatives that could be informative for linkage studies or for determining co-segregation of mutations within families. Subjects of either gender and all ethnic and racial groups will be accepted.

Prenatal specimens (amniocentesis or CVS) will be accepted if they are previously acquired for clinically indicated reasons. Cord blood or placenta specimens may be accepted if they (or a part of them) are not needed for clinical purposes.

Specimens from patients collected at outside institutions may be accepted into the study if they were collected under an IRB-approved protocol at an MPA or FWA institution.

Coded specimens (specimens linked to identifiers but without personal identifiers attached to the sample) may be acquired from other NIH investigators, analyzed, and returned as research results to that investigator.

EXCLUSION CRITERIA:

Patients with typical GCPS or PHS who have demonstrated GLI3 mutations may be excluded from this study. Patients with phenotypes and disorders with a high risk/benefit ratio such as late-onset, neurodegenerative, psychiatric, and cancer-predisposition disorders will be excluded from participation. Similarly, patients who are medically fragile or unable to tolerate travel to the NIH CC will not routinely be eligible for participation. Probands who are adults and decisionally-impaired are ineligible if they do not have a legal guardian who has authority to sign a consent form on their behalf.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001404

Contacts
Contact: Julie Sapp (301) 435-2832 sappj@mail.nih.gov
Contact: Leslie G Biesecker, M.D. (301) 402-2041 lesb@mail.nih.gov

Locations
United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048-1804
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
United States, South Carolina
Greenwood Genetics Center Recruiting
Greenwood, South Carolina, United States, 29646
Turkey
Ankara University School of Medicine Recruiting
Ankara, Turkey
Sponsors and Collaborators
Investigators
Principal Investigator: Leslie G Biesecker, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier: NCT00001404     History of Changes
Other Study ID Numbers: 940193, 94-HG-0193
Study First Received: November 3, 1999
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Pallister-Hall Syndrome
Abnormalities, Multiple
Hypothalamic Hamartoma
Polysyndactyly
Autosomal Dominant
Mutation
Gelastic
Gelastic Seizure
Hypothalamic
Malformations
Polydactyly

Additional relevant MeSH terms:
Pallister-Hall Syndrome
Congenital Abnormalities
Polydactyly
Limb Deformities, Congenital
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Hamartoma
Neoplasms
Hypothalamic Neoplasms
Supratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hypothalamic Diseases
Abnormalities, Multiple

ClinicalTrials.gov processed this record on July 26, 2014