Bardet–Biedl syndrome

Overview

Bardet–Biedl syndrome (BBS) is a rare, multisystem genetic disorder that affects many parts of the body. It is classified as a ciliopathy—disorders caused by defects in the structure or function of cellular cilia. BBS is characterized by a combination of features including retinal degeneration, obesity, polydactyly, kidney abnormalities, and intellectual impairment. The condition is named after Georges Bardet and Arthur Biedl, who independently described the syndrome in the early 20th century. It is inherited in an autosomal recessive pattern and varies in severity from person to person.

Causes

Bardet–Biedl syndrome is caused by mutations in one of at least 20 different genes, all of which are involved in ciliary function. These genes includeBBS1,BBS2,BBS10, and others. Key causes include:

• Mutations in BBS genes responsible for proper function of primary cilia

• Autosomal recessive inheritance – both copies of the defective gene must be inherited for the syndrome to develop

• Consanguinity increases the risk due to shared gene mutations

Symptoms

The clinical features of Bardet–Biedl syndrome vary but typically include a combination of the following:

• Retinal degeneration (often retinitis pigmentosa) – leading to night blindness and progressive vision loss

• Obesity – often begins in early childhood and may be severe

• Polydactyly – extra fingers or toes, typically present at birth

• Kidney abnormalities – structural defects, cystic changes, or chronic kidney disease

• Learning difficulties or intellectual disability

• Hypogonadism – underdeveloped genitalia or delayed puberty in males

• Speech and motor delays

• Behavioral issues in some individuals

Not all individuals with BBS will have all features, and symptom severity can vary greatly.

Diagnosis

Diagnosis is based on clinical criteria and confirmed through genetic testing:

• Clinical assessment identifying characteristic features like polydactyly, obesity, and visual impairment

• Ophthalmologic examination for retinal dystrophy

• Renal ultrasound to assess for kidney malformations or dysfunction

• Genetic testing to identify mutations in known BBS genes

• Developmental and cognitive assessments in children

Early diagnosis is crucial for monitoring and managing complications.

Treatment

There is no cure for Bardet–Biedl syndrome. Treatment is supportive and focuses on managing symptoms and preventing complications:

• Low-vision support and mobility training for progressive visual loss

• Weight management with nutritional support and physical activity

• Renal care including monitoring kidney function and managing hypertension

• Speech and occupational therapy for developmental delays

• Hormonal therapy for delayed puberty or hypogonadism

• Special education and behavioral therapy for cognitive or social challenges

Multidisciplinary care is essential for optimal management.

Prognosis

The prognosis for individuals with Bardet–Biedl syndrome depends on the severity of organ involvement, especially kidney and vision complications:

• Progressive vision loss often leads to legal blindness in adolescence or early adulthood

• Chronic kidney disease can lead to renal failure and significantly impact life expectancy

• Obesity and related complications may contribute to cardiovascular issues

• Early intervention and multidisciplinary care can improve quality of life and functional outcomes

Lifelong monitoring and supportive care are essential for managing this complex condition.