Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
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
WAGR syndrome is a rare genetic disorder characterized by Wilms tumor, aniridia,
 genitourinary anomalies and mental retardation. The syndrome is caused by heterozygous
 contiguous gene deletions of variable size on chromosome 11, involving a region that
 encompasses more than 100 genes, many of which have unknown function in humans. In our
 preliminary studies, we have observed that approximately two-thirds of patients with WAGR
 syndrome have deletion of the gene which encodes brain-derived neurotrophic factor (BDNF),
 and that BDNF haploinsufficiency is associated with obesity and with parent reports of
 hyperphagia and impaired nociception, suggesting that BDNF may play an important role in
 human energy balance as well as pain sensation. We now propose to conduct a comprehensive
 clinical phenotype-genotype study on patients with WAGR syndrome and other 11p deletions. We
 plan to enroll 75 subjects with WAGR syndrome/11p deletions who will undergo evaluations of
 the following systems: metabolic/endocrine, sensation/nociception, ophthalmologic,
 audiologic, neurocognitive, renal/genitourinary, oncologic, dental/craniofacial, cardiac, and
 orthopedic. Genetic testing will be performed on the parents of subjects with WAGR
 syndrome/11p deletion who choose to participate in order to determine if parental origin of
 the deletion influences phenotype. We also plan to enroll 75 healthy subjects as body-size
 matched controls for metabolic studies and 75 patients with isolated aniridia as visually
 impaired controls for neurocognitive studies. We hypothesize that a more complete
 understanding of the correlation between phenotype and genotype could lead to improved
 medical care of these patients through genotype-specific management as well as yield further
 insight into the physiological role of genes in the 11p region.
-  INCLUSION CRITERIA:

 For WAGR/11p deletion subjects:

 1. 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

 2. 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)

 3. 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:

 1. 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)

 2. 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

 3. No chronic medical or psychiatric conditions anticipated to affect results or impede
 study participation

 For aniridia subjects:

 1. Diagnosis of aniridia confirmed by ophthalmologist

 2. 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)

 3. Medically stable, with no chronic medical or psychiatric conditions anticipated to
 affect results or impede study participation

 EXCLUSION CRITERIA:

 For WAGR/11p deletion subjects:

 1. Anorexiant use in preceding 6 months

 2. Greater than 2% body weight loss in preceding 6 months

 3. Pregnancy

 4. 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:

 a) No exclusions other than lack of ability to give consent for participation

 For healthy control subjects:

 1. Anorexiant use in preceding 6 months

 2. Greater than 2% body weight loss in preceding 6 months

 3. Pregnancy

 4. 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:

 1. Anorexiant use in preceding 6 months

 2. Greater than 2% body weight loss in preceding 6 months

 3. Pregnancy

 4. 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