BackgroundWhile obesity is common in the United States, monogenic obesity is rare, accounting for approximately 5% of individuals with obesity. New targeted therapies for genetic forms of obesity are available but there is limited guidance on who requires testing. The aims of this study were to evaluate the prevalence of potentially clinically significant variants among individuals in Pediatric Endocrinology or Medical Weight Center clinics at a single center and to identify clinical characteristics that may make genetic obesity more likely.MethodsChildren and adults who had a genetic test for obesity, Uncovering Rare Obesity Gene panel, ordered during routine clinic visits from December 2019 to March 2021 were identified.ResultsOf the 139 patients with testing ordered, 117 had available results and clinical data. Over 40% (52/117, 44%) had at least one positive result (variant) with a variant that is considered pathogenic, likely pathogenic, or a variant of uncertain significance. No association was detected between age, sex, race, and body mass index (BMI) or BMI z‐score with a variant. Twenty‐six individuals (22%) had one or more variants in genes associated with Bardet Biedl Syndrome, and 8 (6.8%) of them had pathogenic variants, higher than expected.ConclusionOverall, clinical suspicion for genetic obesity is important in determining who requires genetic testing but no clinical factors were found to predict results. While obesity is multifactorial, novel medications for genetic forms of obesity indicate the need for evidence‐based guidelines for who requires genetic testing for obesity.

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Background and ObjectivesBody mass index (BMI) and height are important indices of health. We tested the association between these outcomes and clinical characteristics in Friedreich ataxia (FRDA), a progressive neuromuscular disorder.MethodsParticipants (N = 961) were enrolled in a prospective natural history study (Friedreich Ataxia Clinical Outcome Measure Study). Age- and sex-specific BMI and height Z-scores were calculated using CDC 2000 references for participants younger than 18 years. For adults aged 18 years or older, height Z-scores were also calculated, and absolute BMI was reported. Univariate and multivariate linear regression analyses tested the associations between exposures, covariates, and BMI or height measured at the baseline visit. In children, the superimposition by translation and rotation analysis method was used to compare linear growth trajectories between FRDA and a healthy reference cohort, the Bone Mineral Density in Childhood Study (n = 1,535 used for analysis).ResultsMedian age at the baseline was 20 years (IQR, 13–33 years); 49% (n = 475) were women. A substantial proportion of children (17%) were underweight (BMI-Z < fifth percentile), and female sex was associated with lower BMI-Z (β = −0.34, p < 0.05). In adults, older age was associated with higher BMI (β = 0.09, p < 0.05). Regarding height, in children, older age (β −0.06, p < 0.05) and worse modified Friedreich Ataxia Rating Scale (mFARS) scores (β = −1.05 for fourth quartile vs first quartile, p < 0.01) were associated with shorter stature. In girls, the magnitude of the pubertal growth spurt was less, and in boys, the pubertal growth spurt occurred later (p < 0.001 for both) than in a healthy reference cohort. In adults, in unadjusted analyses, both earlier age of FRDA symptom onset (=0.09, p < 0.05) and longer guanine-adenine-adenine repeat length (shorter of the 2 GAA repeats, β = −0.12, p < 0.01) were associated with shorter stature. Both adults and children with higher mFARS scores and/or who were nonambulatory were less likely to have height and weight measurements recorded at clinical visits.DiscussionFRDA affects both weight gain and linear growth. These insights will inform assessments of affected individuals in both research and clinical settings.