The TEMPO (Tracing the Effect of the MC4 Pathway in Obesity) Registry
The TEMPO (Tracing the Effect of the MC4 Pathway in Obesity) Registry
A voluntary prospective study that will allow registration and follow-up of individuals with
 MC4R pathway genetic obesity.
Potential patients will be referred to coordinating centers by their healthcare provider
 (treating physician, diagnosing physician or primary care physician) and if eligible will be
 invited to enroll in the registry. The Registry Coordinating Center will be responsible for
 obtaining consent from adult patients and caregivers of minor patients (as well as assent
 from minors when appropriate), screening patients and enrolling them in the registry.

 The registry will capture data entered by the patient, the patient's healthcare provider, and
 the patient's caregiver using online (electronic) survey tools administered at baseline, and
 annually thereafter. The patient's healthcare provider will complete the baseline Healthcare
 Provider survey tool, reporting the patient's baseline demographics, medical history,
 clinical information, and disease characteristics. The patient and caregiver will complete
 their dedicated baseline survey tools answering questions on the impact of disease on their
 everyday life. Survey tools include questions on patient and caregiver demographics, patient
 physical activity, patient food and hunger episodes, patient quality of life, and caregiver's
 perspective of disease burden on the family. Registry patients, caregivers, and healthcare
 providers will be contacted annually (approximately every 12 months) by the Registry
 Coordinating Center to complete an online follow-up survey tool including a smaller subset of
 questions from the baseline survey tools.
Inclusion Criteria:

 1. Extreme obesity patients aged 2 years and older.

 2. Extreme obesity defined as:

 1. BMI > 40 kg/m2 in patients 18 years of age or older.

 2. BMI value that is >1.4 times the corresponding age/gender 95th percentile value
 in patients who are 2 through 17 years of age.

 3. At least one of the following genotypes:

 1. Bi-allelic (homozygous or compound heterozygous) POMC, PCSK1, LEPR variants
 leading to the physician-confirmed diagnosis of either POMC or LEPR deficiency
 obesity.

 2. The presence of high-confidence, high-impact genetic variations (homozygote,
 compound heterozygote, heterozygote or composite heterozygote [i.e., heterozygous
 variants in more than a single gene]) in these same 3 genes (POMC, PCSK1 and
 LEPR) associated with the clinical presentation of extreme obesity

 3. The presence of other high-confidence, high-impact genetic variations
 (homozygote, compound heterozygote, heterozygote or composite heterozygote in the
 MC4R gene or other upstream MC4R-pathway genes and selected variants downstream
 in the MC4R-pathway (Table 1) that are carried by extreme obesity patients who do
 not demonstrate specific syndromic obesity clinical presentations. Selected
 Bardet-Biedl syndrome (BBS1 through BBS21) genetic variants or Alström syndrome
 (ALMS) genetic variants possibly contributing to non-syndromic forms of clinical
 extreme obesity will be eligible for enrollment.

 4. Study participant and/or parent or caregiver can understand and comply with the
 requirements of the study, and able to understand and sign the written informed
 consent (IC)/assent, after being informed about the study.

 Exclusion Criteria:

 1. Patients with syndromic forms of obesity such as Bardet-Biedl syndrome or Alström
 syndrome. These patients will be referred to existing registries for these specific
 syndromic obesity (e.g., Clinical Registry in Bardet-Biedl syndrome [CRIBBS] for BBS
 patients).

 2. Individual is, in the opinion of the study investigator, not suitable to participate
 in the study.