Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions

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