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Bardet-Biedl Syndrome - Nonsyndromic Inherited Retinal Diseases & Widefield Fundus Autofluorescence

Bardet-Biedl Syndrome - Nonsyndromic Inherited Retinal Diseases & Widefield Fundus Autofluorescence

November 02, 2021

Bardet Biedl Syndrome is a rare genetic disorder with highly variable symptoms which may include retinal degeneration, obesity, reduced kidney function, polydactyly (extra digits of the hands or feet) among many other features.

While there are more than 20 genes associated with BBS, the underlying cause regardless of gene is malfunction of primary cilia, a key component of cellular communication. BBS is thus categorized as a ciliopathy, or a disease of the cilia.

The retina is a multi-layered sensory tissue that lines the back of the eye. Its main function is the transduction of light energy into an electrical potential change, via a process known as phototransduction.

The light-sensitive elements of the retina are the photoreceptor cells. The retina contains two types of photoreceptors, rods and cones. Rods (approximately 120 million in the human eye) are in charge of night vision, while cones (6 to 7 million in the human eye) are in charge of visual acuity and color vision.

The highest cone concentration is found in the central region of the retina, known as the macula. Photoreceptors are highly compartmentalized cells, with the nucleus and other cellular organs located in the inner segment (IS), while the entire phototransduction machinery is included in the outer segment (OS).

Inherited retinal diseases (IRDs), which are among the most common genetic diseases in humans, define a clinically heterogeneous group of disorders, which cause visual loss due to improper development, dysfunction or premature death of the retinal photoreceptors.

IRDs are distinguished by several factors, including the type and location of affected cells and the timing of disease onset.

Widefield fundus autofluorescence (FAF) can be very useful for confirming the diagnoses of rare disorders.

Bardet-Biedl syndrome (BBS) is a disorder in which the affected patients can be obese and have hypogonadotropic hypogonadism, polydactylism, developmental delay, genitourinary abnormalities, renal disease, and retinal degeneration.

Kimberly Stepien, MD, associate professor of ophthalmology in the Department of Ophthalmology and Visual Sciences at the University of Wisconsin-Madison, explained that patients with BBS can often receive a misdiagnosis of a nonsyndromic disease, such as retinitis pigmentosa, despite having potentially life-threatening syndromic findings.

These misdiagnoses can result in delayed screening for systemic problems. The retinas in patients with BBS can have findings that appear similar to those in patients with retinitis pigmentosa, such as classic bone spicules.

However, more subtle retinal degenerative changes can be missed during a clinical examination. “Widefield FAF can highlight peripheral degeneration and macular atrophy,” she said.

BBS study Stepien and colleagues reviewed the charts of 9 patients aged 18 to 65 years with genetically confirmed BBS for the medical and ocular histories, findings from the clinical examinations, and ocular imaging, including widefield Optos color fundus photos, FAF, and spectral domain optical coherence tomography.

The investigation found that before BBS was diagnosed, two-thirds of patients (6 of 9) received a diagnosis of a nonsyndromic inherited retinal disease despite the presence of systemic abnormalities and/or family histories that suggested a syndromic disease.

The examination of the 6 patients with a misdiagnoses showed only subtle peripheral pigment changes. Widefield FAF showed varying patterns of speckled hypo-FAF in the periphery of all patients with BBS.

In addition, macular abnormalities (ie, macular atrophy and bull’s-eye maculopathy) were seen in all patients and were highlighted by variable FAF changes, Stepien reported. The investigators concluded, “Patients with BBS are often misdiagnosed with nonsyndromic disease despite having potentially life-threatening syndromic findings.

Along with detailed medical and family histories, specific imaging findings on widefield FAF can aid in the diagnosis of BBS in adult patients with suspected inherited retinal diseases by better delineating macular degeneration patterns and unearthing extensive peripheral hypo-FAF changes when clinical examinations findings are subtle.”