Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy with a highly variable phenotype that evolves significantly during childhood and/or adolescence.26,27 It’s estimated that as many as 2500 people in the United States are living with BBS.24 Obesity and hyperphagia are two common features of BBS that can seriously impact the overall health and quality of life of these patients.26,27
“It’s a constant need to eat. And that’s when she started sneaking foods... We ended up getting some locks and putting them on our pantry and on the fridge.”
Olivia, whose daughter Adalissa is living with BBS
- Typically early onset by age 5
Hyperphagia (insatiable hunger)29
- Preoccupation with food
- Excessive food-seeking behavior
Visual impairment (93%)27
Rod-cone dystrophy that presents as atypical retinitis pigmentosa with early macular involvement
- Symptoms generally appear in the first decade of life and ultimately lead to legal blindness by teens/early adulthood
- Progressive visual loss manifests initially as night blindness, followed by photophobia, and finally a loss of central/color vision
- Changes in the retina can be detected by electroretinography (ERG) by age 2
- Significant changes are typically not evident until after age 5
Renal anomalies (53%)
- Renal phenotype is variable. Generally involves cystic tubular disease and anatomical malformations27
Cognitive impairment (>50%)26
- Learning difficulties
- Speech delay
- Developmental delay
- Genital anomalies
- Diabetes mellitus
- Dental anomalies
- Left ventricular hypertrophy or congenital heart disease
- Brachydactyly or syndactyly
- Mild spasticity (especially lower limbs)
- Strabismus, cataracts, or astigmatism
- Ataxia or poor coordination
- Anosmia or hyposmia
- Polyuria or polydipsia
- Hepatic fibrosis
BBS has a highly variable phenotype that evolves significantly during childhood and/or adolescence.
Phenotype can vary between siblings.
Obesity and hyperphagia in BBS:
Likely driven by impairment of a key signaling pathway that regulates hunger56
- Plays a key role in regulating hunger, satiety, and energy expenditure
- Is activated by leptin, a neurosignaling hormone generated in adipose tissue
- BBS genes help traffic the leptin receptor to the cell surface of POMC neurons, enabling leptin activation
- Once activated, POMC neurons activate MC4R neurons, leading to satiety
Take a deeper look inside the MC4R pathway
Hyperphagia in BBS
Hyperphagia is a key symptom associated with obesity in BBS and often has an early onset, typically by age 5.29
General dimensions of hyperphagia22
Excessive food-seeking behavior
Preoccupation with food
Significant distress when denied food
Patients with BBS suffer from hyperphagia, exhibiting extreme food-seeking behavior.29
Total hyperphagia score and subscale scores in 13 patients with BBS*
Adapted from Sherafat-Kazemzadeh R et al. Pediatr Obes. 2013;8(5):e64-e67.
Hyperphagia and food-seeking behavior are different in BBS
Individuals living with BBS have signiﬁcantly greater hyperphagia scores overall (total) and in the behavioral dimension compared to matched controls.
*A hyperphagia questionnaire assessing 13 patients with BBS and 23 nonsyndromic controls with similar age, sex, and BMI z-score. After adjustment for age, sex, race, and BMI z-score, total score (P=0.032) and behavior subscale (P=0.003) remained significantly different.
Consider the Understanding the Impact of Hyperphagia tool for discussions with individuals living with BBS and their families.
Obesity in BBS
As many as 9 out of 10 patients with BBS are affected by obesity.27
BMI z-scores by gender and age group in children with BBS (n=628)45
Severe obesity has an early onset, typically beginning in childhood by age 5, and persists into adulthood45
Obesity further complicates management of comorbidities.
Chronic obesity and hyperphagia management are challenging in patients with BBS.
Diet and behavioral modiﬁcations
Target neuropathways outside of the MC4R pathway
May be complicated due to associated comorbidities
Listen to Dr. Robert Haws discuss hyperphagia and obesity in BBS
Pathway deficiencies in BBS
Searching for answers
The Role of the MC4R Pathway
MC4R=melanocortin-4 receptor; POMC=proopiomelanocortin.
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