Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions

NCT00758108 | Completed

• 2 other identifiers: 08021308-CH-0213
• Study Type: observational
• Target: 197
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore conditions caused by the absence of certain genes on chromosome 11. These conditions include WAGR syndrome, which is characterized by a kidney tumor called Wilm s tumor, aniridia (absence of the iris of the eye), genital and urinary abnormalities, mental retardation, and possibly other symptoms. This study will examine how the genes on chromosome 11 affect people and whether the absence of specific genes is associated with specific symptoms. Healthy normal volunteers, people with isolated aniridia, and people with WAGR or another chromosome 11 gene deletion may be eligible for this study. Participants must be at least 6 years old. Parents of patients may also participate for genetic studies. Participants undergo some or all of the following procedures, depending on whether they are a child, adult, healthy volunteer or parent of a patient:

• Medical history and physical examination, eye examination, blood, urine and saliva tests, electrocardiogram (EKG) and electroencephalogram (EEG)
• X-rays, scans and other tests to measure body composition (fat, muscle and bone development and thickness) and MRI to examine the eyes and the brain and to measure abdominal fat
• Ultrasound studies of the kidneys, ovaries and uterus (in females) and testes (in males)
• Meal tests, food diaries and food preference tests
• Questionnaires about eating and sleep habits, personality and character traits and responses to pain and injury
• Neuropsychological tests
• Tests of resting metabolic rate, energy expenditure and glucose (sugar) tolerance
• Hot and cold sensitivity tests, vibration sensitivity test, cold tolerance test and smell identification test
• Eye and hearing tests
• Nerve conduction studies and study of sensory information conduction from peripheral nerves to the spinal cord and brain
• Computer photography
• Evaluation by sub-specialists (e.g., endocrinologist, ophthalmologist, physiatrist, neurologist or others) as indicated by the patient s medical history and test results

Conditions

WAGR Syndrome; Wilm's Tumor; Aniridia; Urogenital Abnormalities; Mental Retardation

Keywords

Genotype/Phenotype Correlation; Energy Homeostasis; Nociception; Obesity; Behavior and Neurocognition; WAGR Syndrome; Wilm's Tumor; Aniridia; Mental Retardation; Urogenital Abnormalities; Healthy Volunteer

Eligibility Criteria

• Age: 2 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For WAGR/11p deletion subjects:
• Diagnosis of WAGR/11p deletion confirmed by prior genetic testing or clinical history consistent with WAGR syndrome (Wilms Tumor and/or genitourinary anomalies plus aniridia). Genetic diagnosis will be confirmed at the NIH, if not done previously
• Age greater than or equal to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight \<12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
• Medically stable (so that the patient can safely undergo planned testing); if history of Wilms tumor, must be \>6 months since completion of chemotherapy and must be considered in remission by primary oncologist caring for the patient
• For parents of WAGR/11p deletion subjects:
• a)Biological parent of child with WAGR/11p deletion able to give consent for self participation
• For healthy control subjects:
• Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight \<12 kg) blood draw, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
• No chronic medications. Use of as-needed and over-the-counter medications will be reviewed on a case-by-case basis by the Principal Investigator
• No chronic medical or psychiatric conditions anticipated to affect results or impede study participation
• For aniridia subjects:
• Diagnosis of aniridia confirmed by ophthalmologist
• Age greater than or eqaul to 2 years old (Subjects age 2-6y will only have an outpatient evaluation, one 60 mL (or 5 mL/kg if weight \<12 kg) blood draw, eye examination, and cognitive, behavioral, and psychiatric assessment performed; subjects age 6y and older will participate in full protocol)
• Medically stable, with no chronic medical or psychiatric conditions anticipated to affect results or impede study participation

You may not qualify if:

• For WAGR/11p deletion subjects:
• Anorexiant use in preceding 6 months
• Greater than 2% body weight loss in preceding 6 months
• Pregnancy
• Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
• For parents of WAGR/11p deletion subjects:
• For healthy control subjects:
• Anorexiant use in preceding 6 months
• Greater than 2% body weight loss in preceding 6 months
• Pregnancy
• Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study
• For aniridia subjects:
• Anorexiant use in preceding 6 months
• Greater than 2% body weight loss in preceding 6 months
• Pregnancy

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2003 Dec 15;21(24):4579-85. doi: 10.1200/JCO.2003.06.096.

  PMID: 14673045 BACKGROUND

• Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005 Oct;116(4):984-8. doi: 10.1542/peds.2004-0467.

  PMID: 16199712 BACKGROUND

• Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T. Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics. 2007 Sep;90(3):397-406. doi: 10.1016/j.ygeno.2007.05.004. Epub 2007 Jul 12.

  PMID: 17629449 BACKGROUND

• Sapio MR, Iadarola MJ, LaPaglia DM, Lehky T, Thurm AE, Danley KM, Fuhr SR, Lee MD, Huey AE, Sharp SJ, Tsao JW, Yanovski JA, Mannes AJ, Han JC. Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity. Pain. 2019 May;160(5):1070-1081. doi: 10.1097/j.pain.0000000000001485.

  PMID: 30855519 DERIVED

• Han JC, Reyes-Capo DP, Liu CY, Reynolds JC, Turkbey E, Turkbey IB, Bryant J, Marshall JD, Naggert JK, Gahl WA, Yanovski JA, Gunay-Aygun M. Comprehensive Endocrine-Metabolic Evaluation of Patients With Alstrom Syndrome Compared With BMI-Matched Controls. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2707-2719. doi: 10.1210/jc.2018-00496.

  PMID: 29718281 DERIVED

MeSH Terms

Conditions

WAGR Syndrome; Wilms Tumor; Aniridia; Urogenital Abnormalities; Intellectual Disability; Obesity; Behavior

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Eye Abnormalities; Eye Diseases; Eye Diseases, Hereditary; Iris Diseases; Uveal Diseases; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight

Study Officials

• Jack A Yanovski, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2008
• First Posted: September 23, 2008
• Study Start: September 11, 2008
• Study Completion: April 29, 2015
• Last Updated: December 12, 2019

Record last verified: 2015-04-29

Locations

US (1)