Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Characterization of Angelman Syndrome

Summary: Angelman Syndrome (AS) is a developmental disorder that is caused by a deficiency of a maternally transmitted gene. It is inherited at birth, and affects movement, speech, and social demeanor. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over an extended period of time.

Detailed description: AS is a developmental disorder that affects movement, speech, and social demeanor. The disorder is caused by a deficiency of a maternally transmitted gene and is inherited at birth. Children with AS, however, are often not diagnosed until they are between 3 and 7 years old. Symptoms of AS may include, but are not limited to, functionally severe developmental delay; speech impairments; movement or balance problems; and behavioral uniqueness, including any combination of frequent laughter or smiling, apparent happy demeanor, easily excitable personality, hand flapping movements, and short attention span. There are four molecular variations of AS, but past clinical studies have been inconsistent in highlighting the phenotypic differences between them. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over a period of 5 to 10 years. The study will also attempt to establish genotype-phenotype correlations, which might aid in future clinical care of AS patients.
  Participation in this observational study will be limited to current or future patients at one of the five study sites. A clinical evaluation will be performed at baseline, including a general patient history, physical and neurological examinations, a nutritional assessment, neuro-imaging, electroencephalography, laboratory testing, and neurodevelopmental testing. A blood sample or mucosal sample will also be taken at baseline to acquire DNA for potential genetic testing. All assessments except the neuro-imaging, electroencephalography, and blood sampling will be repeated at yearly study visits for as long as funding can be secured. In addition, participants will be photographed and perhaps videotaped on a yearly basis in order to document clinical phenotypes and any neurologic abnormalities. Participants may be followed-up for a total of 10 years.

Eligibility: Inclusion Criteria:
  1. Molecular diagnosis of Angelman syndrome OR
  2. Meets all major diagnostic criteria for Angelman Syndrome and 3 of the 6 minor criteria:
  Major Criteria:
  -  Functionally severe developmental delay
  -  Speech impairment; none or minimal words used
  -  Movement or balance disorder
  -  Behavioral uniqueness, frequent laughs/smiling, excitable personality, hand flapping, short attention span
  Minor Criteria:
  -  Deceleration in head circumference growth (post-natal)
  -  Seizures (myoclonic, absence, drop, tonic-clonic)
  -  Abnormal EEG (with patterns suggestive of AS, or hypsarrhythmia)
  -  Sleep disturbance
  -  Attraction to or fascination with water
  -  Drooling
  Exclusion Criteria:
  -  Does not meet diagnostic criteria for Angelman Syndrome
  -  Other medical or genetic disorders (except autism)
  -  Born extremely premature

Relevance to patient case: not relevant