Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy with a highly variable phenotype that evolves significantly during childhood and/or adolescence.28,29 It’s estimated that as many as 2500 people in the United States are living with BBS.25 Obesity and hyperphagia are two common features of BBS that can seriously impact the overall health and quality of life of these patients.28,29

“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

BBS is inherited in an autosomal recessive manner


BBS is an autosomal recessive disease.29 Nearly 30 genes have been found to be associated with BBS.28

Typical mode of inheritance for BBS28,45

Typical mode of inheritance for BBS Typical mode of inheritance for BBS

Affected individuals have a variant in both copies of a BBS gene28,45

Common features

The presence and severity of clinical features can vary greatly across individuals. Signs and symptoms can include:4,28-30,46,52

Obesity (72%-92%)46

  • Typically early onset by age 5

Hyperphagia (insatiable hunger)4

  • Preoccupation with food
  • Excessive food-seeking behavior

Visual impairment (93%)29

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

Postaxial polydactyly (63%-81%)

  • Often the only dysmorphic feature present at birth29
  • Extra digit(s) are generally surgically removed in the first year46

Renal anomalies (53%)

  • Renal phenotype is variable. Generally involves cystic tubular disease and anatomical malformations29

Cognitive impairment (>50%)28

  • Learning difficulties
  • Speech delay
  • Developmental delay

Other features29,51

  • 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 hunger57

Functional pathway signaling the hypothalamus in response to leptin release to signify satiety

Functional MC4R pathway signaling1,57,58

Functional pathway signaling the hypothalamus in response to leptin release to signify satiety Functional pathway signaling the hypothalamus in response to leptin release to signify satiety
Impaired MC4R pathway may result in hyperphagia and weight gain

Impaired signaling in BBS1,4,58

Impaired MC4R pathway may result in hyperphagia and weight gain

The MC4R pathway1,57

  • Plays a key role in regulating hunger, satiety, and energy expenditure
  • Is activated by leptin, a neurosignaling hormone generated in adipose tissue

BBS genes play a critical role in MC4R pathway signaling1,57,58

  • 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

Loss of BBS gene function impairs signaling

  • Individuals with BBS inherit 2 nonfunctional copies of a BBS gene, which are the result of a disease-causing variant in each copy29,45
  • Loss of BBS gene function can impair MC4R pathway signaling1,4,58

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 5.4

General dimensions of hyperphagia23

General dimensions of hyperphagia, behaviors.


Excessive food-seeking behavior

General dimensions of hyperphagia, drive.


Preoccupation with food

General dimensions of hyperphagia, severity


Significant distress when denied food

Patients with BBS suffer from hyperphagia, exhibiting extreme food-seeking behavior.4

Total hyperphagia score and subscale scores in 13 patients with BBS*

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.

Download tool

Obesity in BBS

Obesity is common in BBS and can worsen comorbidities28,29,46,47

As many as 9 out of 10 patients with BBS are affected by obesity.29

BMI z-scores by gender and age group in children with BBS (n=628)46

BMI z-scores by gender and age group in children with BBS

Severe obesity has an early onset, typically beginning in childhood by age 5, and persists into adulthood46

Obesity further complicates management of comorbidities.



Renal impairment




Not all interventions address the likely underlying pathology driving obesity in BBS1,28,48-51

Chronic obesity and hyperphagia management are challenging in patients with BBS.

Diet and behavioral modifications

Diet and behavioral modifications

Diet and exercise are not always enough when living with a rare genetic disease of obesity like BBS



Not all treatments target the MC4R pathway, a root cause of obesity and hunger in people living with BBS57

Bariatric surgery

Bariatric surgery

May be complicated due to associated comorbidities

Listen to Dr. Robert Haws discuss hyperphagia and obesity in BBS

BBS can be diagnosed based on clinical features


BBS can be diagnosed based on clinical features.4,29,30,52 Genetic testing can help provide additional evidence to support diagnosis and may help identify siblings with BBS.29,52,53

Learn more


Find out about a treatment option for obesity due to BBS.

Learn More



Pathway deficiencies in BBS

Searching for answers

The Role of the MC4R Pathway

MC4R=melanocortin-4 receptor; POMC=proopiomelanocortin.

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