Introduction

Bardet-Biedl syndrome (BBS) is a rare genetic condition that can impair multiple organs, including the brain, eyesight, reproductive organs and kidneys.¹ This disorder can impair the quality of life of the patient in late adolescence or early adulthood by making them experience physical impairments, complications with organ function, obesity, hormonal imbalances, vision problems and other health issues.²

Etiology

BBS is an autosomal recessive hereditary condition. This condition is mostly seen in consanguineous genes, where patients have an increased risk of inheriting the two copies of a recessive gene. Individuals with BBS may or may not have a family history. The most common feature seen in these patients is retinal dystrophy.^1,3

Primary Features of BBS

• Retinal dystrophy
• Truncal obesity
• Cognitive impairment 
• Postaxial polydactyly
• Hypogonadism
• Genitourinary anomalies
• Renal abnormalities

Secondary features in BBS

• Speech disorder/delay
• Strabismus/cataracts/astigmatism
• Brachydactyly/syndactyly
• Developmental delay
• Polyuria/polydipsia (nephrogenic diabetes insipidus)
• Ataxia/poor coordination/imbalance
• Mild spasticity (lower limbs)
• Diabetes mellitus
• Dental crowding/hypodontia/high-arched palate
• Left ventricular hypertrophy/congenital heart disease
• Hepatic fibrosis

What is retinal dystrophy in BBS?

Retinal dystrophy is a condition which is characterised by the degeneration of the retina’s photoreceptor cells. Retinal dystrophies can be grouped into different categories depending on the degeneration of specific photoreceptors.

They are: 

• Rod-dominated disease (rod cells are affected)
• Cones-dominated disease (cone cells are affected)
• Generalised form ( both cells are affected)

Retinal dystrophy is crucial in the diagnosis of BBS. Most of the BBS cases show the early onset of vision problems which gets worse over time due to both rods and cone dysfunction.⁴

Signs and Symptoms

• Blurred vision
• Night blindness since early childhood
• Tunnel vision or loss of peripheral vision
• Impaired color vision
• Reduced vision (first decades of life)
• Legally blind (best-corrected vision <6/60 ) in the third decade of life
• Difficulty with tasks that require detailed vision, such as reading and recognising face

Patients with BBS typically have vision problems in their early childhood that is around 8 to 9 years of age and almost all of them may lose their complete vision by their thirties.³

Understanding the cause of Impaired night vision  and colour vision

The rods and cones cells which have special cells called cilia, help facilitate the transport of essential molecules which is necessary in the process called phototransduction (light is converted into electrical signals).

The proteins, which are encoded by BBS genes, are involved in the structure and function of cilia. The mutation in these genes can lead to defective function, which leads to the disruption of the transport process within photoreceptor cells (rods and cones).⁵

Rods are sensitive to light and are important for vision in low-light conditions. Patients with retinal dystrophy in BBS have night blindness due to the affected rods, which help them see in low light or at night.^3,6

Cones are responsible for colour vision and it is important for the determination of colour of different wavelengths. The cones are concentrated in the macula (central part of the retina). In patients with BBS, as retinal dystrophy progresses the cone cells begin to degenerate leading to impaired color vision.^3,7

These specialised cells with outer segments work like sensory antennas, which help in capturing light and turning it into visual signals. Disruption of the phototransduction pathway due to defective cilia can impair rod and cone cells leading to impaired colour vision and night blindness.

Other eye problems in BBS

• Myopia
• Astigmatism
• Strabismus
• Cataract

Diagnosis

The various signs and symptoms of BBS at different ages make the diagnosis difficult. The people won’t be able to recognise polydactyly (extra fingers or toes) as a symptom of BBS. The developing vision problems by 8-9 years old and obesity by 2-3 years old often raise concerns about BBS. 

In many individuals, the BBS diagnosis occurs by the eye examination when a person visits with vision problems.

Patient history 

Individuals may complain of decreased vision, night blindness, gradual peripheral vision loss, and impaired colour vision.

Ophthalmologic examination

Ophthalmologists may conduct certain tests to look for characteristic signs of retinal dystrophy.

Fundus examination  

The ophthalmologist will use ophthalmoscopy to look at the back surface of the eye (retina) to check for pigmentary retinal changes.

Electroretinography (ERG)

ERG is one the most important tests in diagnosing retinal dystrophy. This is used to measure the electrical response of the rods and cones in the retina. In individuals with BBS, ERG often has a decreased or absent response, indicating retinal dystrophy.

Visual field testing

This test helps in assessing your field of vision,the individuals with BBS will show a constricted visual field.

Colour vision testing

This test assesses the ability to discriminate colours of different wavelengths. These include Ishihara color plates and the Fransworth-munsell 100 hue test.

Optical coherence tomography

This test provides the high-resolution image of your retina (back surface of your eye), which helps in the detailed examination of retinal layers and the detection of structural abnormalities.

Genetic testing 

This test helps in confirming the diagnosis by identifying the mutations in BBS genes.  

Treatment

The treatment of retinal dystrophy in Bardet-biedl syndrome (BBS) is primarily focused on managing the symptoms and slowing the progression of the disease, as there is currently no cure. 

Symptomatic Treatments

Vision Aids 

Some individuals might have low vision, where low vision aids can help in Improving your remaining vision. Low vision aids such as magnifying glasses, telescopic lenses and screen readers.

Adaptive Technologies 

The quality of life can be improved in patients with BBS by using adaptive technologies, including voice-activated devices and software to assist in daily life activities.

Managing other BBS-related symptoms 

Addressing other BBS-related symptoms, such as obesity, renal abnormalities and cognitive impairment through multidisciplinary approach, can improve overall health and quality of life.Emerging Therapies

There are different therapies and treatments are emerging to improve the quality of life and overall health of the individuals affected with BBS which includes gene therapy, and stem cell therapy.

Supportive Care

Patient Education and Counseling

• Educating individuals and their families about the disease, its progression and management strategies is crucial for effective care and support 
• There are many support groups and organisations which offer emotional support and practical advice, along with resources for the management and improvement of the disease to improve the overall health and quality of life 
• Individuals must be counselled about genetics, which can help them understand the inheritance pattern, risks for the coming generations and implications for family members

Summary 

Bardet-Biedl syndrome (BBS) is a rare genetic disorder that can impair multiple organs, including the brain, eyesight, reproductive organs and kidneys.The BBS syndrome can have various primary and secondary features, including retinal dystrophy, obesity, polydactyly, hypogonadism. Retinal dystrophy is crucial and can help in the diagnosis of BBS. The retinal dystrophy in individuals with BBS is due to the rods and cone dysfunction. The individuals exhibit various signs and symptoms, which can hinder the quality of life and overall health. The diagnosis and treatment is crucial to improve the quality of life of the individuals affected with retinal dystrophy in Bardet-Biedl syndrome (BBS).