Chromosome 18 Clinical Research Center (Chromosome18)

• Primary [ Time Frame: Ongoing ]
  Provide definitive medical and education resources for the families of individuals with chromosome 18 abnormalities
  
  

Procedure: Determination of growth hormone status
Growth hormone stimulating testing using Arginine and Clonidine, Corticotrophin releasing hormone stimulation test
Procedure: Measurement of growth, thyroid and sex hormone levels
Gonadotrophin releasing hormone stimulation test Thyroid testing - T4, TSH, T3 uptake, and anti-thyroidal antibodies baseline sample - no medication administered
Procedure: Behavior and neuropsychometric evaluations
evaluation by neuropsychologist, standardized testing geared to study participant's age, abilities and past medical history
Procedure: Audiological and ear, nose and throat examination
neurotological exam, behavioral audiometry, immittance audiometry, assessment of the function of the inner ear using otoacoustic emissions, Auditory brain responses
Procedure: Magnetic resonance imaging of the brain
MRI of the brain - standard clinical procedure
Procedure: Dysmorphology evaluation
Genetic evaluation with picture and measurements, physical exam
Procedure: Neurology examination
physical examination including observation of balance, coordination and reflexes.
Procedure: Dental evaluation
Visual detal inspection with panorex X-ray of the entire mouth
Procedure: Speech pathology evaluation
Standardized speech & language tests and naturalistic assessment procedures.
Procedure: Psychiatric evaluation
Psychiatric interview about history of psychiatric and medical illnesses, family psychiatric and medical history, demographic info also obtained
Procedure: Orthopedic evaluation
Physical exam by orthopedic surgeon and a dysplasia series of radiographs including AP and lateral radiographics of the feet, APs of the knees, pelvis, thoracic lumbar spine and chest, laterals of thoracic lumbar and cervical spine, lateral of the skull, AP and lateral of the forearm, bone age evaluation with radiograph of left hand
Procedure: Ophthalmologic evaluation
exam will determine visual acuity using one of the following: Snellen chart, Allen acuity, target acuity, optokinetic nystagmus (OKN), or Teller acuity depending on study participants ability level. Motility/alignment will also be determined using cover/uncover test. Pupils examined using slit lamp. Dilated fundus exam and cycloplegic refraction which will require dilating drops in both eyes. Cyclogen 1% and NeuSynephrine 2.5% are using. In children less than 6 months old, less potent mydriatrics and cycloplegics are used Cyclogel 0.5% or Tropicamide 1%. Intraocular pressure will be measured in adults and cooperative teens using applanation tonometry. A topical anesthetic will be used to perform this measurement.
Procedure: Gastrointestinal evaluation
physical exam and medical history by board certified gastroenterologist.

Protocol Summary:

The hypotheses are:

1. 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
2. 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:

1. to be the international medical and education resource for the families of individuals with chromosome 18 abnormalities;
2. to perform and facilitate both clinical and basic research relating to the disorders of chromosome 18; and
3. 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:

1. perform genotypic molecular analysis on the DNA of the subjects and their biological parents to determine the genotype of the affected individual;

2. gather comprehensive clinical data on individuals with chromosome 18 abnormalities including:

   1. determination of growth hormone levels;
   2. measurement of corticotrophin, thyroid and sex hormones;
   3. psychiatric and neuropsychological evaluations;
   4. audiology and ENT testing;
   5. brain MRI scan;
   6. genetic dysmorphology examination;
   7. neurology exam;
   8. dental exam;
   9. speech pathology evaluation;
   10. gastrointestinal exam;
   11. orthopedic exam;
   12. 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.