Chromosome 18 Clinical Research Center

Protocol Summary:

The hypotheses are:

• growth hormone (GH) deficiency in children with chromosome 18 deletions is accompanied by cognitive and microstructural abnormalities of the brain that can be ameliorated by GH treatment; and
• the physical and behavioral findings in individuals with abnormalities of chromosome 18 are due to the genes that present in a non-diploid number.

Therefore, correlation of the physical and behavioral findings with the extent of the deletion will help identify the genes involved. An understanding of the molecular mechanisms of the phenotype will provide the insight necessary to devise appropriate therapies.

Our goals are:

• to be the international medical and education resource for the families of individuals with chromosome 18 abnormalities;
• to perform and facilitate both clinical and basic research relating to the disorders of chromosome 18; and
• to devise treatments to help these individuals overcome the negative effects of their chromosome abnormality.

To attain these goals, the study has the following specific aims:

• perform genotypic molecular analysis on the DNA of the subjects and their biological parents to determine the genotype of the affected individual;
• gather comprehensive clinical data on individuals with chromosome 18 abnormalities including:

• determination of growth hormone levels;
• measurement of corticotrophin, thyroid and sex hormones;
• psychiatric and neuropsychological evaluations;
• audiology and ENT testing;
• brain MRI scan;
• genetic dysmorphology examination;
• neurology exam;
• dental exam;
• speech pathology evaluation;
• gastrointestinal exam;
• orthopedic exam;
• ophthalmology exam.

The phenotypical assessment will be longitudinal; therefore, the participants will have a wide age range. This extensive range plus the fact that some participants will be assessed multiple times means that not all components of the clinical studies will be appropriate for every subject at every visit.

Inclusion criteria

• Must have a confirmed diagnosis of Chromosome 18 or be the parent/guardian of a child with Chromosome 18
• Subject must be at least one year of age to participate in the clinical examination aspect of the study (due to issues of venous access and blood volume required to complete studies)
• General health status: good

Exclusion criteria

• Pregnant women
• Dead fetuses
• Prisoners
• Non-viable neonates or neonates of uncertain viability