Symptoms and General Pathology

All Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Musculoskeletal Diseases

Neoplasms

Rare Diseases

Syndrome

Congenital Abnormalities

Seizures

Polydactyly

Hamartoma

Abnormalities, Multiple

Pallister-Hall Syndrome

Limb Deformities, Congenital

Musculoskeletal Abnormalities

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Hypothalamic Diseases

Autosomal Dominant Multiple Pterygium Syndrome

Leslie G Biesecker, M.D.

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.

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.

Phenotype and Etiology of Pallister-Hall Syndrome

Genetic and Clinical Studies of Congenital Anomaly Syndromes

National Human Genome Research Institute (NHGRI)

ExAblate 4000 System

Sophie Kopec

Robert Keating

Roger Packer

The Focused Ultrasound Team

John Ragheb, MD

Ian Miller, MD

Luis Mendoza, MD

Toba Niazi, MD

Sanjiv Bhatia, MD

Pat Dean, ARNP

Ziad Khatib, MD

Ann Hsylop, MD

Nolan Altman, MD

Christian Bauer, MD

Frank Wang, MD

Paquine Sadeghi, MD

The goal of this prospective, non-randomized, single-arm, feasibility study is to develop data to evaluate the safety and feasibility of ExAblate 4000 treatment of benign intracranial tumors which require clinical intervention in pediatric and young adult subjects.

Indication of Use: Ablation of benign intracranial tumors in children and young adults which are ExAblate accessible.

The goal of this prospective, non-randomized, single-arm, feasibility study is to develop data to evaluate the safety and feasibility of ExAblate 4000 treatment of benign intracranial tumors which require clinical intervention in pediatric and young adult subjects.

Indication of Use: Ablation of benign intracranial tumors in children and young adults which are ExAblate accessible.

This is a feasibility study intended to collect data for use in the development of future studies. As such, no formal statistical hypothesis or hypothesis testing is proposed. The purpose of this study is to evaluate the safety and feasibility of managing benign brain tumor size using ExAblate 4000 treatment of progressing benign intracranial tumors which require clinical intervention in pediatric and young adult subjects.

A Feasibility Safety Study of Benign Centrally-Located Intracranial Tumors in Pediatric and Young Adult Subjects

A Feasibility Safety Study Using the ExAblate 4000 System in the Management of Benign Centrally-Located Intracranial Tumors Which Require Clinical Intervention in Pediatric and Young Adult Subjects

Safety will be assessed by tabulation of treatment related adverse events. All adverse events at least possibly procedure related will also be examined in detail for patterns of occurrence.

ExAblate procedure will demonstrate feasibility along with measurement of tumor volumes at follow-up as compared to the baseline MRI.

Any changes in physical examination performed by a physician.

Any changes in neurological examination performed by the neurologist/neurosurgeon.

Changes in confrontational visual field testing performed by a physician

Impression of change as the result of the treatment by a physician

Impression of change as the result of the treatment by the subject

InSightec

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phenotype and Etiology of Pallister-Hall Syndrome	NCT00001404	Malformations Multiple Abnorm... Polydactyly		-	National Institutes of Health Clinical Center (CC)
Phenotype and Etiology of Pallister-Hall Syndrome	NCT00001404	Malformations Multiple Abnorm... Polydactyly		-	National Institutes of Health Clinical Center (CC)
A Feasibility Safety Study of Benign Centrally-Located Intracranial Tumors in Pediatric and Young Adult Subjects	NCT03028246	Benign Centrall...	ExAblate 4000 S...	8 Years - 22 Years	InSightec
A Feasibility Safety Study of Benign Centrally-Located Intracranial Tumors in Pediatric and Young Adult Subjects	NCT03028246	Benign Centrall...	ExAblate 4000 S...	8 Years - 22 Years	InSightec
A Feasibility Safety Study of Benign Centrally-Located Intracranial Tumors in Pediatric and Young Adult Subjects	NCT03028246	Benign Centrall...	ExAblate 4000 S...	8 Years - 22 Years	InSightec
Phenotype and Etiology of Pallister-Hall Syndrome	NCT00001404	Malformations Multiple Abnorm... Polydactyly		-	National Institutes of Health Clinical Center (CC)

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