Sleep Abnormalities in Rare Genetic Disorders: AS, RTT, and PW

Subjects with AS, RTT or PWS and normal siblings (controls) will be recruited for study
participation.

Subjects will be recruited from the Rare Disease Clinical Research Network (RDCRN)
consortium registries for AS, RTT and PWS. The RDCRN registries provide listings of
individuals currently enrolled in the RDCRN along with clinical and genetic diagnosis,
medical history and contact information.

The RDCRN consortium sites for AS, RTT and PWS will participate in the study. These sites
will recruit study participants, obtain informed consent and administer the sleep
questionnaires. Institutional Review Board (IRB) approval will be obtained at each RDCRN
consortium site.

"Subjects" is defined as those children with a diagnosis of AS, PWS, and RTT. Subjects will
be divided into separate study arms based upon their medical diagnosis. Study arms will
consist of: 1) AS group, 2) PWS group, 3) RTT group, and 4) control group. "Control group"
is defined as normal healthy siblings of subjects.

Study participants and parents/guardians will be asked to complete the study questionnaires
during the clinic visit. The questionnaires are brief and should not be difficult to
complete. It is anticipated that the questionnaires can be completed in 15-30 minutes. If
parents are unable to complete the questionnaires at the time of their scheduled clinic
visit they will be asked to take the questionnaires home to complete and to mail them back
to the research team. When the research team receives the returned questionnaires they will
be reviewed for completion. If questions are skipped or left blank, a member of the research
team will call the family to complete the missed questions over the phone.

Parents/guardians are allowed to answer the questions on behalf of the study participants
and will be asked to answer all the questions for each age-appropriate questionnaire in
order for the responses to be scored correctly. Subjects with AS, RTT and PWS and normal
siblings will complete the same questionnaire forms.

Study participants will be administered the questionnaires again in 12-24 months at a
follow-up RDCRN clinic visit or by mail to assess the natural history of their sleep
behavior and any sleep disorders.

Study participants identified as having a potential severe sleep disorder based on
questionnaire responses will be contacted or sent a letter by the study investigators and
advised to see a sleep specialist for further evaluation.

Potential "Subjects" must be members of the RDCRN consortium registries with available
contact and clinical diagnostic information on file. These individuals will be invited to
participate in the study at their next regularly scheduled RDCRN visit.

Study recruitment will continue for one year. Subjects with a clinical diagnosis of AS, RTT
or PWS, or normal siblings of these individuals will be recruited for study participation.

The sample size of study participants, including controls, will be based upon the number of
individuals currently enrolled in the RDCRN consortium registries. Currently the combined
number of individuals in the AS, RTT and PWS RDCRN consortium registries is 1082. The
breakdown by disorder is: 678 RTT, 172 AS, 141 PWS. Final sample size will be the total
number of subjects consented during the one year recruitment period. A projected enrollment
total would be approximately 1,000 total individuals ( 500 subjects including 300 RTT, 100
AS, 100 PWS & 500 controls).

Inclusion Criteria:

Eligible Inclusion Criteria - Subjects

1. Enrollment in a RDCRN consortium registry for either AS, RTT or PWS.

2. Have a clinical diagnosis of AS, RTT or PWS, or be a normal sibling of an individual
with AS, RTT or PWS who is enrolled in the study.

3. Be between 0 to18 years of age inclusive.

4. Be English-speaking (study questionnaires will only be available in English).

Inclusion Criteria - Controls

1. Must have a sibling with either AS, RTT or PWS enrolled in the study.

2. Must not have a diagnosis of any neurological disorder.

3. Be between 0 to18 years of age inclusive

4. Be English-speaking (study questionnaires will only be available in English).

Exclusion Criteria:

Exclusion Criteria - Subjects

1. No clinical diagnosis of AS, RTT, or PWS.

2. Diagnosis of a severe genetic disorder in addition to AS, RTT, or PWS.

3. Be over 18 years of age inclusive.

Exclusion Criteria - Controls

1. Diagnosis of a neurological disorder.

2. Diagnosis of a severe genetic disorder.

3. Be over 19 years of age inclusive.