Genetic variants in the melanocortin-4 receptor (MC4R) pathway can impair the regulation of hunger, food intake, satiety and energy expenditure. This can lead to hyperphagia (pathological, insatiable hunger) and a decreased energy expenditure, resulting in early-onset, severe obesity, regardless of environmental and lifestyle factors.^1,2

The root cause of early-onset, severe obesity is often underdiagnosed. Access to appropriate tools and proactive identification of clinical features can help aid diagnosis and move those living with a rare MC4R pathway disease, onto their appropriate care path.¹

BBS is a rare MC4R pathway disease characterised by a range of clinical features, such as rod-cone dystrophy, that evolve over time. Obesity (present in 72-92% of patients) and hyperphagia are among the most distressing manifestations of BBS, with a substantial burden on patients and caregivers.^2,3

Additional clinical features include:^2,4,6

Primary clinical features: 

• Genital anomalies
• Learning difficulties
• Obesity
• Polydactyly
• Renal anomalies
• Rod-cone dystrophy

Secondary clinical features: 

• Anosmia or hyposmia
• Ataxia or poor coordination
• Brachydactyly or syndactyly
• Dental anomalies
• Developmental delay
• Diabetes mellitus
• Hepatic fibrosis
• Left ventricular hypertrophy or congenital heart disease
• Mild spasticity (especially lower limbs)
• Polyuria or polydipsia
• Speech delay or speech impairments
• Strabismus, cataracts, astigmatism

Despite the urgent need for early diagnosis to reduce the impact of future comorbidities, significant delays exist in BBS diagnosis due to lack of awareness and the slow emergence of certain clinical features.⁵

Variants in at least 26 genes have been identified and are known to cause BBS.⁵ Clinical guidelines recommend genetic testing to inform diagnosis and appropriate interventions in patients with the clinical features of hyperphagia and early-onset, severe obesity. A genetic diagnosis of BBS can make a considerable difference to an individual's life by:^6,7,8

• Improving access to appropriate care for hyperphagia and early-onset, severe obesity
• Reducing the social stigma of obesity and providing coping strategies for managing stigmatisation
• Empowering the individual and carers to understand the root cause of their condition and make informed decisions about their care
• Allowing for preventive or prophylactic screening of associated conditions