Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
Condition: WAGR Syndrome; Wilm's Tumor; Aniridia; Urogenital Abnormalities; Mental Retardation
MeSH terms: Wilms Tumor; WAGR Syndrome; Intellectual Disability; Aniridia; Urogenital Abnormalities; Congenital Abnormalities; Syndrome
Study type: Observational

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
    

Detailed description: 
      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.
    

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