The purpose of this screening study is to identify people who have a rare genetic cause of obesity - specifically three genetic variants (a change in the DNA structure) of the POMC, PCSK1 and LepR genes that are currently known to result in obesity.

This screening study will not include any investigational drugs. You will be asked to provide a DNA sample and answer some questions about your medical history and hunger.

Individuals who meet any of the following inclusion criteria may be eligible:

1. Participant aged 2 or older.

2. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent/assent.

3. ≥40kg/m2 (age 18 and older) or 1.4x 95th percentile of BMI for age (ages 2-17) - with evidence of hunger or hyperphagia by screening surveys, indicated by a patient or observer score at or greater than midpoint of scale.

   o Individuals with clinical evidence of RGDO (per appendix 4) but do not meet the BMI criteria may be included if the investigators estimation and proband demonstrates a BMI Z-score difference of >1 between proband and any other sibling; and/or the proband demonstrates a BMI difference >10 kg/m2 between proband and parents.

4. ≥50 kg/m2 (age 18 and older) or 1.5x 95th percentile of BMI for age (ages 2-17). Cohorts included under this criteria include ≥50-60 kg/m2 (age 18 and older) or 1.5x 95th percentile of BMI for age (ages 2-17) and ≥60 kg/m2 (age 18 and older) or 1.6x 95th percentile of BMI for age (ages 2-17).

5. ≥ 40 kg/m2 (pre-operative) or 1.4x 95th percentile of BMI for age (ages 12-17) with history of bariatric surgery or planned surgery within 3 months (prior to or following screening).

Individuals who meet any of the following exclusion criteria will not be eligible:

1. Prior craniopharyngioma or other hypothalamic brain region surgery or surgeries/procedures for brain tumor, i.e., ventriculoperitoneal shunt and radiation therapy
2. Diagnosis of Prader-Willi syndrome

The objective is to identify individuals with severe, early onset morbid obesity (EOMO), who are aged 2 years of age or older, and are suspected to be either homozygous, compound heterozygous or heterozygous for loss of function mutations in the POMC, PCSK1 or LepR gene, leading to a clinical presentation of Melanocortin 4 (MC4) pathway deficiency obesity. Individuals may be contacted for further assessment of clinical features (including questionnaires on past weight and medical history and current hunger and feeding behavior symptoms) and/or participation in future Rhythm clinical trials.