Chromosome 18 Clinical Research Center (Chromosome18)

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Our vision, that of the researchers at the University of Texas Health Science Center at San Antonio, is that every person with a chromosome 18 abnormality will have an autonomous and healthy life. Our mission is to provide families affected by chromosome 18 abnormalities with comprehensive medical and educational information. Our goals are to provide definitive medical and education resources for the families of individuals with chromosome 18 abnormalities; perform and facilitate groundbreaking clinical and basic research relating to the syndromes of chromosome 18; and to provide treatments to help these individuals overcome the effects of their chromosome abnormality.

Condition or disease

Intervention/treatment

Chromosome Aberrations; Growth Hormone Deficiency; Hypomyelination

Procedure: Determination of growth hormone status; Procedure: Measurement of growth, thyroid and sex hormone levels; Procedure: Behavior and neuropsychometric evaluations; Procedure: Audiological and ear, nose and throat examination; Procedure: Magnetic resonance imaging of the brain; Procedure: Dysmorphology evaluation; Procedure: Neurology examination; Procedure: Dental evaluation; Procedure: Speech pathology evaluation; Procedure: Psychiatric evaluation; Procedure: Orthopedic evaluation; Procedure: Ophthalmologic evaluation; Procedure: Gastrointestinal evaluation

Detailed Description:

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.

Study Design

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Study Type :	Observational
Estimated Enrollment :	1000 participants
Observational Model:	Other
Time Perspective:	Other
Official Title:	The Chromosome 18 Clinical Research Center
Study Start Date :	September 1993
Estimated Primary Completion Date :	December 2025
Estimated Study Completion Date :	December 2025

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Intervention Details:

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.

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

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

Biospecimen Retention:   Samples With DNA

blood specimens are collected from study participant and both biological parents if available and are processed for DNA and to establish cell lines

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

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

Criteria

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

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Jannine D. Cody, Ph.D.	210-567-9220	cody@uthscsa.edu
Contact: Daniel E. Hale, M.D.	210-567-5284	hale@uthscsa.edu

Locations

United States, Texas
University of Texas Health Science Center at San Antonio	Recruiting
San Antonio, Texas, United States, 78229
Contact: Jannine D Cody, Ph.D. 210-567-9220 cody@uthscsa.edu
Contact: Daniel E Hale, M.D. 210-567-5284 hale@uthscsa.edu
Principal Investigator: Jannine D. Cody, Ph.D.
Sub-Investigator: Peter T. Fox, M.D.
Principal Investigator: Daniel E. Hale, M.D.
Sub-Investigator: Brian P Perry, M.D.

Sponsors and Collaborators

The University of Texas Health Science Center at San Antonio

Investigators

Principal Investigator:	Jannine D. Cody, Ph.D.	The University of Texas Health Science Center at San Antonio
Principal Investigator:	Daniel E. Hale, M.D.	The University of Texas Health Science Center at San Antonio

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Click here for more information about this study: The Chromosome 18 Clinical Research Center 

The Chromosome 18 Registry & Research Society is a lay advocacy organization composed primarily of the parents of individuals with one of the chromosome 18 abnormalities. 

Publications of Results:

Cody JD, Semrud-Clikeman M, Hardies LJ, Lancaster J, Ghidoni PD, Schaub RL, Thompson NM, Wells L, Cornell JE, Love TM, Fox PT, Leach RJ, Kaye CI, Hale DE. Growth hormone benefits children with 18q deletions. Am J Med Genet A. 2005 Aug 15;137(1):9-15.

Lancaster JL, Cody JD, Andrews T, Hardies LJ, Hale DE, Fox PT. Myelination in children with partial deletions of chromosome 18q. AJNR Am J Neuroradiol. 2005 Mar;26(3):447-54.

Kochunov P, Lancaster J, Hardies J, Thompson PM, Woods RP, Cody JD, Hale DE, Laird A, Fox PT. Mapping structural differences of the corpus callosum in individuals with 18q deletions using targetless regional spatial normalization. Hum Brain Mapp. 2005 Apr;24(4):325-31.

Schaub RL, Hale DE, Rose SR, Leach RJ, Cody JD. The spectrum of thyroid abnormalities in individuals with 18q deletions. J Clin Endocrinol Metab. 2005 Apr;90(4):2259-63. Epub 2005 Jan 25.

Cody JD, Hale DE. Precision in phenotyping and genotyping. Am J Med Genet A. 2004 Dec 15;131(3):313.

Gunn SR, Mohammed M, Reveles XT, Viskochil DH, Palumbos JC, Johnson-Pais TL, Hale DE, Lancaster JL, Hardies LJ, Boespflug-Tanguy O, Cody JD, Leach RJ. Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q. Am J Med Genet A. 2003 Jul 1;120A(1):127-35.

Schaub RL, Reveles XT, Baillargeon J, Leach RJ, Cody JD. Molecular characterization of 18p deletions: evidence for a breakpoint cluster. Genet Med. 2002 Jan-Feb;4(1):15-9.

Schaub RL, Cody JD, Hale DE. Growth disorders in the chromosome 18 syndromes. Highlights 9:3-5, 2001

Hermesch CB, Cody JT, Cody JD. Dental caries history in nine children with chromosome 18p deletion syndrome. Spec Care Dentist. 2000 Mar-Apr;20(2):53-5.

Hale DE, Cody JD, Baillargeon J, Schaub R, Danney MM, Leach RJ. The spectrum of growth abnormalities in children with 18q deletions. J Clin Endocrinol Metab. 2000 Dec;85(12):4450-4.

Cody JD, Reveles XT, Hale DE, Lehman D, Coon H, Leach RJ. Haplosufficiency of the melancortin-4 receptor gene in individuals with deletions of 18q. Hum Genet. 1999 Nov;105(5):424-7.

Wang Z, Cody JD, Leach RJ, O'Connell P. Gene expression patterns in cell lines from patients with 18q- syndrome. Hum Genet. 1999 Jun;104(6):467-75.

Cody JD, Ghidoni PD, DuPont BR, Hale DE, Hilsenbeck SG, Stratton RF, Hoffman DS, Muller S, Schaub RL, Leach RJ, Kaye CI. Congenital anomalies and anthropometry of 42 individuals with deletions of chromosome 18q. Am J Med Genet. 1999 Aug 27;85(5):455-62.

Brkanac Z, Cody JD, Leach RJ, DuPont BR. Identification of cryptic rearrangements in patients with 18q- deletion syndrome. Am J Hum Genet. 1998 Jun;62(6):1500-6.

Keppler-Noreuil KM, Carroll AJ, Finley SC, Descartes M, Cody JD, DuPont BR, Gay CT, Leach RJ. Chromosome 18q paracentric inversion in a family with mental retardation and hearing loss. Am J Med Genet. 1998 Apr 13;76(5):372-8.

Cody JD, Hale DE, Brkanac Z, Kaye CI, Leach RJ. Growth hormone insufficiency associated with haploinsufficiency at 18q23. Am J Med Genet. 1997 Sep 5;71(4):420-5.

Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ, Fox PT. Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency. Am J Med Genet. 1997 Jul 25;74(4):422-31.

Cody JD, Pierce JF, Brkanac Z, Plaetke R, Ghidoni PD, Kaye CI, Leach RJ. Preferential loss of the paternal alleles in the 18q- syndrome. Am J Med Genet. 1997 Mar 31;69(3):280-6.

Ghidoni PD, Hale DE, Cody JD, Gay CT, Thompson NM, McClure EB, Danney MM, Leach RJ, Kaye CI. Growth hormone deficiency associated in the 18q deletion syndrome. Am J Med Genet. 1997 Mar 3;69(1):7-12.

Carter E, Heard P, Hasi M, Soileau B, Sebold C, Hale DE, Cody JD. Ring 18 molecular assessment and clinical consequences. Am J Med Genet A. 2015 Jan;167A(1):54-63. doi: 10.1002/ajmg.a.36822. Epub 2014 Oct 22.

Cody JD, Sebold C, Heard P, Carter E, Soileau B, Hasi-Zogaj M, Hill A, Rupert D, Perry B, O'Donnell L, Gelfond J, Lancaster J, Fox PT, Hale DE. Consequences of chromsome18q deletions. Am J Med Genet C Semin Med Genet. 2015 Sep;169(3):265-80. doi: 10.1002/ajmg.c.31446. Epub 2015 Aug 3. Review.

Cody JD, Hale DE. Making chromosome abnormalities treatable conditions. Am J Med Genet C Semin Med Genet. 2015 Sep;169(3):209-15. doi: 10.1002/ajmg.c.31447.

Hasi-Zogaj M, Sebold C, Heard P, Carter E, Soileau B, Hill A, Rupert D, Perry B, Atkinson S, O'Donnell L, Gelfond J, Lancaster J, Fox PT, Hale DE, Cody JD. A review of 18p deletions. Am J Med Genet C Semin Med Genet. 2015 Sep;169(3):251-64. doi: 10.1002/ajmg.c.31445. Epub 2015 Aug 6.

Sebold C, Soileau B, Heard P, Carter E, O'Donnell L, Hale DE, Cody JD. Whole arm deletions of 18p: medical and developmental effects. Am J Med Genet A. 2015 Feb;167A(2):313-23. doi: 10.1002/ajmg.a.36880. Epub 2015 Jan 14.

Cody JD, Hasi M, Soileau B, Heard P, Carter E, Sebold C, O'Donnell L, Perry B, Stratton RF, Hale DE. Establishing a reference group for distal 18q-: clinical description and molecular basis. Hum Genet. 2014 Feb;133(2):199-209. doi: 10.1007/s00439-013-1364-6. Epub 2013 Oct 5.

Responsible Party:	The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:	NCT00227253 History of Changes
Other Study ID Numbers:	Chromosome 18; IRB: 990-9000-318 ( Other Identifier: UTHSCSA IRB )
First Posted:	September 27, 2005
Last Update Posted:	September 29, 2017
Last Verified:	September 2017

Keywords provided by The University of Texas Health Science Center at San Antonio:

Phenotype; Growth; Genotype; Chromosome 18

Additional relevant MeSH terms:

Dwarfism, Pituitary; Dwarfism; Chromosome Aberrations; Chromosome Disorders; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases	Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Pathologic Processes; Congenital Abnormalities; Genetic Diseases, Inborn; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs