Introduction

Bardet-Biedl Syndrome (BBS) is a rare genetic disorder that affects multiple systems in the body. It’s named after the doctors who first described the condition. BBS is part of a group of diseases known as ciliopathies, caused by defects in the structure or function of cilia, tiny hair-like structures on the surface of cells that play crucial roles in various bodily functions. The most common features of BBS include vision loss due to retinitis pigmentosa, obesity, kidney problems, and intellectual disability. Another key feature is the presence of limb abnormalities, particularly polydactyly having extra fingers or toes.¹

Understanding these limb abnormalities is essential for early diagnosis, treatment, and management, improving the quality of life for those affected. This article provides an in-depth overview of polydactyly and other limb abnormalities associated with BBS, explaining their genetic basis, clinical presentation, and management options.

Genetic basis of bardet-biedl syndrome

Genes associated with BBS

BBS is caused by gene mutations, with at least 22 different BBS genes identified so far. The most common genes include BBS1, BBS2, BBS10, and BBS12.¹ These genes are involved in the formation and function of cilia, which are crucial for the development and maintenance of multiple organs and systems in the body, including the limbs. When these genes are mutated, the resulting dysfunction of cilia can lead to the various symptoms seen in BBS, including limb abnormalities like polydactyly.¹

Mechanism of limb development in BBS

The development of limbs in the embryo is a complex process that relies on the proper functioning of cilia. These structures help in signalling pathways that guide the formation of the limb bud, which eventually develops into arms, legs, hands, and feet. In BBS, defective cilia disrupt these signalling pathways, leading to abnormal limb development, such as extra fingers or toes (polydactyly), short fingers or toes (brachydactyly), or fused fingers or toes (syndactyly).¹

Polydactyly in bardet-biedl syndrome

Prevalence and types of polydactyly

Polydactyly is a common feature of BBS, occurring in about 60-70% of individuals with the syndrome¹. It involves the presence of extra digits on the hands or feet. There are two main types:

• Preaxial Polydactyly: Extra digit on the thumb or big toe side.
• Postaxial Polydactyly: Extra digit on the little finger or toe side, which is more common in BBS¹.

Clinical presentation

In BBS, polydactyly often presents at birth and can affect one or both hands or feet. The extra digit may be fully functional or just a small, non-functional piece of tissue. The severity and functionality of the extra digit vary, with some individuals having fully formed extra fingers or toes, while others may have small, underdeveloped ones. Polydactyly in BBS is often accompanied by other limb abnormalities, which can complicate movement and dexterity.

Figure 1. Types of Polydactyl (Preaxial, Central, Postaxial - left to right)

Diagnostic imaging and identification

Diagnosing polydactyly in BBS usually occurs through physical examination at birth. However, prenatal diagnosis is possible using ultrasound imaging to detect limb abnormalities early in pregnancy. Postnatally, X-rays may be used to assess the bones of the extra digit, particularly if surgical intervention is being considered. Early diagnosis is critical for planning the best course of treatment and management, especially when the extra digit interferes with normal function.

Other limb abnormalities in bardet-biedl syndrome

Brachydactyly

Brachydactyly, or shortened fingers or toes, is another limb abnormality associated with BBS. It is caused by the abnormal development of the bones in the fingers or toes, leading to digits that are shorter than average.¹ This condition can affect fine motor skills and may require adaptive techniques or interventions to improve hand or foot function.

Syndactyly

Syndactyly refers to the fusion of two or more fingers or toes. This can range from partial fusion, where only the skin is joined, to complete fusion, where the bones are also joined. In BBS, syndactyly is less common than polydactyly but still a significant limb abnormality that can impact function¹. Treatment typically involves surgical separation of the digits to improve hand or foot function.

Other skeletal anomalies

In addition to polydactyly, brachydactyly, and syndactyly, individuals with BBS may experience other skeletal abnormalities, such as clinodactyly (curved fingers or toes) and limb length discrepancies¹. These anomalies can further complicate movement and require specialised care, such as physical therapy or orthopaedic interventions.

Pathophysiology of limb abnormalities in BBS

Ciliopathy and its role

BBS is classified as a ciliopathy because defects in cilia primarily cause it. Cilia are vital for various cellular processes, including the proper development of limbs. They are involved in signalling pathways such as the Hedgehog and Wnt pathways, which are crucial for the patterning and growth of the limb bud during embryonic development. In BBS, defective cilia lead to disrupted signalling in these pathways, resulting in limb abnormalities characteristic of the syndrome.⁴

Molecular pathways 

• Hedgehog signalling pathway: This pathway plays a critical role in the growth and patterning of limbs. Mutations in BBS genes can disrupt Hedgehog signalling, leading to abnormal digit formation and limb structure⁴
• Wnt signalling pathway: Involved in the regulation of cell fate and movement during limb development. Defects in this pathway can contribute to the various limb abnormalities seen in BBS, such as polydactyly and syndactyly⁴

Management of polydactyly and limb abnormalities in BBS

Surgical interventions

Surgery is often recommended for individuals with polydactyly or other significant limb abnormalities, especially when the extra digit interferes with function or causes discomfort³. The type of surgery depends on the severity and nature of the abnormality:

• Simple Excision: For non-functional extra digits
• Complex Reconstruction: For fully formed digits requiring bone and tendon adjustments

The goal of surgery is to improve function and appearance while minimizing complications. Post-surgery, physical therapy may be needed to enhance movement and strength.

Non-surgical management

Not all limb abnormalities in BBS require surgery. Non-surgical options include:

• Orthopedic Devices: Splints or braces to support affected limbs
• Physical Therapy: Exercises to improve strength, coordination, and dexterity
• Occupational Therapy: Techniques to assist with daily activities, particularly for those with significant hand or foot involvement

Prognosis and long-term care

Proper management allows individuals with BBS to lead fulfilling lives despite their limb abnormalities. Early intervention, including surgery and physical therapy, can significantly improve outcomes. However, regular follow-up is essential to monitor any changes or complications that may arise over time.

Research and advances in understanding limb abnormalities in BBS

Recent genetic discoveries

Ongoing research continues to uncover new genetic mutations associated with BBS, providing deeper insights into the condition. These discoveries have the potential to lead to new treatments, such as gene therapy, which could one day correct the underlying genetic defects that cause limb abnormalities³.

Animal models and experimental studies

Animal models, such as mice, are extensively used in BBS research to study the effects of specific gene mutations on limb development. These studies have provided valuable information about the disease mechanism and are helping researchers develop targeted therapies³.

Summary

Bardet-Biedl Syndrome is a complex genetic disorder with various manifestations, including significant limb abnormalities like polydactyly, brachydactyly, and syndactyly. Understanding these abnormalities' genetic basis and pathophysiology is crucial for early diagnosis and effective management. Advances in research continue to provide hope for improved treatments and outcomes. Multidisciplinary care, including surgical and non-surgical approaches, is essential for managing these abnormalities and enhancing the quality of life for individuals with BBS.

FAQs

What causes polydactyly in bardet-biedl syndrome?

Polydactyly in BBS is caused by genetic mutations that affect the function of cilia, tiny hair-like structures essential for limb development. These mutations disrupt normal signalling pathways, leading to the formation of extra digits.

Can polydactyly in BBS be treated?

Yes, polydactyly can be treated, usually through surgery to remove the extra digit if it interferes with function or causes discomfort. Sometimes, non-surgical interventions like splints or physical therapy may also be used.

Is bardet-biedl syndrome curable?  

Currently, there is no cure for BBS. However, many of its symptoms, including limb abnormalities, can be managed with appropriate treatment, improving the quality of life for those affected.