Phenotype and Etiology of Pallister-Hall Syndrome

NCT00001404 | Completed

• 2 other identifiers: 94019394-HG-0193
• Study Type: observational
• Target: 1,170
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Malformations; Multiple Abnormalies; Polydactyly

Keywords

Abnormalities, Multiple; Hypothalamic Hamartoma; Polysyndactyly; Autosomal Dominant; Mutation; Gelastic; Gelastic Seizure; Hypothalamic; Malformations; Polydactyly; Pallister-Hall Syndrome

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (4)

Cedars Sinai Medical Center

Los Angeles, California, 90048-1804, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Greenwood Genetics Center

Greenwood, South Carolina, 29646, United States

Location

Ankara University School of Medicine

Ankara, Turkey (Türkiye)

Location

Related Publications (3)

• Kang S, Graham JM Jr, Olney AH, Biesecker LG. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat Genet. 1997 Mar;15(3):266-8. doi: 10.1038/ng0397-266.

  PMID: 9054938 BACKGROUND

• Kang S, Allen J, Graham JM Jr, Grebe T, Clericuzio C, Patronas N, Ondrey F, Green E, Schaffer A, Abbott M, Biesecker LG. Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. J Med Genet. 1997 Jun;34(6):441-6. doi: 10.1136/jmg.34.6.441.

  PMID: 9192261 BACKGROUND

• Biesecker LG, Graham JM Jr. Pallister-Hall syndrome. J Med Genet. 1996 Jul;33(7):585-9. doi: 10.1136/jmg.33.7.585. No abstract available.

  PMID: 8818945 BACKGROUND

MeSH Terms

Conditions

Polydactyly; Abnormalities, Multiple; Hypothalamic hamartomas; Syndactyly; Multiple Pterygium Syndrome, Autosomal Dominant; Epilepsies, Partial; Pallister-Hall Syndrome

Condition Hierarchy (Ancestors)

Limb Deformities, Congenital; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hamartoma; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Hypothalamic Diseases

Study Officials

• Leslie G Biesecker, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: August 18, 1994
• Study Completion: January 7, 2016
• Last Updated: December 16, 2019

Record last verified: 2016-01-07

Locations

TU (1); US (3)