Updated BBS criteria seek to speed diagnosis for affected families
New algorithm gives doctors clearer clinical and genetic testing guidance
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Updated diagnostic criteria may help clinicians recognize Bardet-Biedl syndrome earlier and reduce delays for affected families. (Photo by iStock)
A team of international medical specialists and patient-led organizations has developed a simplified decision-making process incorporating updated clinical and genetic evidence to help clinicians worldwide reach a timely and accurate diagnosis of Bardet-Biedl syndrome (BBS).
The development of the new evidence-based diagnostic algorithm was described in the study, “Streamlining Diagnosis of Bardet–Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria,” published in the American Journal of Medical Genetics Part A.
New criteria may reduce yearslong diagnostic delays
“Early and accurate BBS diagnosis can make an enormous difference for affected families,” Tim Ogden, executive director of the Bardet Biedl Syndrome Foundation and a study author, said in a press release from Rhythm Pharmaceuticals. “I know from personal experience that diagnosis opens the door to appropriate clinical care and support services, and better outcomes are possible the earlier that happens.” Rhythm markets Imcivree (setmelanotide), the only FDA-approved treatment for adults and children ages 2 and older with obesity due to BBS to help reduce body weight and keep it off. The company funded writing and editorial assistance for the publication, as well as the systematic literature review used in the study.
BBS is a rare genetic disorder caused by problems in primary cilia, antenna-like structures on cells that help cells sense their surroundings and send signals. It’s a multisystem condition characterized by symptoms such as progressive vision loss, obesity, extra fingers or toes, kidney abnormalities, cognitive impairments, and genital or urinary tract anomalies.
A BBS diagnosis is largely based on recognizing its clinical features, along with tests to evaluate cognitive function, vision, and kidney function. Genetic testing can confirm many cases, with studies reporting positive results in about 80% or more of clinically diagnosed patients who undergo testing.
Still, the median age at diagnosis is around 9 years, and in some regions with limited access to genetic testing, a diagnosis may be delayed until late adolescence or early adulthood.
“Even in 2026, too many families spend years searching for answers before they get an accurate diagnosis,” Ogden said.
The original diagnostic criteria for BBS were published in 1999, with subsequent updates. Since then, researchers have learned more about how BBS presents across different ages and how differently its symptoms can appear.
“The original diagnostic criteria were pivotal in defining Bardet-Biedl syndrome over two decades ago; however, advances in our understanding of this disease now support a more practical and integrated approach,” said Philip Beales, MD, emeritus professor at University College London, in the U.K., who was involved in the development of both the original diagnostic criteria and the new diagnostic algorithm.
Experts update major and minor signs of BBS
The new algorithm was developed by a team of international specialists in obesity, hormone disorders, genetics, eye and kidney diseases, and neuropsychology, along with representatives from patient-led organizations in the U.S., U.K., and the Netherlands.
Diagnostic features of BBS were gathered using two methods: a literature review and data from the Clinical Registry Investigating Bardet-Biedl Syndrome (NCT02329210).
Under the updated criteria, a clinical BBS diagnosis requires either four major criteria or three major criteria plus two minor criteria. The major criteria are:
- progressive disease affecting the light-sensitive tissue at the back of the eye (retinal dystrophy)
- obesity at any age or overweight in children under 2
- kidney and urinary tract anomalies at birth or chronic kidney disease
- reduced function of the reproductive organs (hypogonadism) or genital anomalies
- neurodevelopmental or neurocognitive problems
- extra fingers or toes on the outer side of the hand or foot (postaxial polydactyly)
Because extra fingers or toes are often surgically corrected in infancy, clinicians should look for surgical scars in older patients, the authors noted.
The minor criteria are:
- reduced ability of the kidneys to concentrate urine or chronic urinary retention in adults
- shortened or fused fingers and/or toes
- hearing loss
- laterality defects, such as organs positioned on the opposite side of the body
- absent or reduced sense of smell
- dental anomalies
- distinctive facial features
- metabolic dysfunction-associated steatotic liver disease (MASLD), a condition marked by fat accumulation in the liver
Two counting rules apply: urine concentration defects cannot be counted separately in a person with kidney and urinary tract anomalies or chronic kidney disease, and MASLD cannot be counted separately in a person with obesity.
Genetic testing can help confirm BBS diagnosis
If a person meets the clinical diagnostic criteria, genetic testing is not required to confirm the diagnosis, though it’s strongly recommended. A diagnosis can also be established through a positive genetic test result — meaning pathogenic or likely pathogenic variants affecting both copies of a BBS-related gene — combined with at least one major criterion, “provided that genetic findings should be interpreted in the context of the patient’s clinical presentation, age, family history, and overlap with related [cilia-affecting diseases],” the researchers wrote.
Representatives of BBS patient organizations also noted that key factors associated with a delayed diagnosis include:
- dismissal of early symptoms
- difficulties recognizing or reporting symptoms due to patients’ own sensory issues
- hard-to-measure effects of vision loss and hyperphagia (insatiable hunger) on cognitive assessments
- cultural stigma around excessive weight gain or developmental delays
“These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS,” the team wrote.
The organizations emphasized that early diagnosis provides significant benefits, including access to treatment, validation for families, and connection to support communities. Still, they noted that overinterpreting specific genetic findings and focusing too much on worst-case outcomes are recurring problems in how diagnoses are communicated to families.
“This algorithm offers clearer guidance to support earlier diagnosis, which is essential for timely management and care,” Beales said.
