Bardet-Biedl syndrome: Weight patterns and genetics in a rare obesity syndrome.
BACKGROUND
Bardet-Biedl syndrome (BBS) is a rare genetic disorder that severely inhibits primary cilia function. BBS is typified by obesity in adulthood, but pediatric weight patterns, and thus optimal periods of intervention, are poorly understood.


OBJECTIVES
To examine body mass differences by age, gender, and genotype in children and adolescents with BBS.


METHODS
We utilized the largest international registry of BBS phenotypes. Anthropometric and genetic data were obtained from medical records or participant/family interviews. Participants were stratified by age and sex categories. Genotype and obesity phenotype were investigated in a subset of participants with available data.


RESULTS
Height and weight measurements were available for 552 unique individuals with BBS. The majority of birth weights were in the normal range, but rates of overweight or obesity rapidly increased in early childhood, exceeding 90% after age 5. Weight z-scores in groups >2 years were above 2.0, while height z-scores approached 1.0, but were close to 0.0 in adolescents. Relative to those with the BBS10 genotype, the BBS1 cohort had a lower BMI z-score in the 2-5 and 6-11 age groups, with similar BMI z-scores thereafter. Children with biallelic loss of function (LOF) genetic variants had significantly higher BMI z-scores compared to missense variants.


CONCLUSION
Despite normal birth weight, most individuals with BBS experience rapid weight gain in early childhood, with high rates of overweight/obesity sustained through adolescence. Children with LOF variants are disproportionally affected. Our findings support the need for earlier recognition and initiation of weight management therapies in BBS.
['Pomeroy|Jeremy|J|', 'Krentz|Anthony D|AD|', 'Richardson|Jesse G|JG|', 'Berg|Richard L|RL|', 'VanWormer|Jeffrey J|JJ|', 'Haws|Robert M|RM|0000-0001-8007-3362']
D000293:Adolescent D000367:Age Factors D020788:Bardet-Biedl Syndrome D001827:Body Height D015992:Body Mass Index D001835:Body Weight D018833:Chaperonins D002648:Child D002675:Child, Preschool D005260:Female D005819:Genetic Markers D005838:Genotype D006801:Humans D007223:Infant D007231:Infant, Newborn D008137:Longitudinal Studies D008297:Male D008869:Microtubule-Associated Proteins D063766:Pediatric Obesity D010641:Phenotype D015995:Prevalence D012042:Registries D012307:Risk Factors D012737:Sex Factors
Bardet-Biedl syndrome genetics obesity overweight missense variants loss of function variants