{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:08:56Z","timestamp":1791216536367,"version":"4.1.0"},"reference-count":9,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"\n Summary<\/jats:title>\n Bardet\u2013Biedl syndrome (BBS) is a rare, autosomal recessive, multisystem non-motile ciliopathy of progressive onset. It is primarily characterised by rod\u2013cone dystrophy, early-onset obesity and related complications, postaxial polydactyly, renal and genitourinary abnormalities, learning disabilities, and hypogonadism. The diagnosis is based on Beales\u2019 modified diagnostic criteria. We present a case of two monozygotic female twins, 17 years of age at presentation, referred for obesity since childhood. The initial hormonal work-up was negative and no dysmorphic features were noted. They were diagnosed with exogenous obesity. However, after ophthalmologic problems became apparent, rod\u2013cone dystrophy was observed and genetic testing was performed. A mutation in the BBS2 gene led to the diagnosis of BBS, although the full diagnostic criteria were not met. This case not only highlights the need to raise awareness for BBS but also exposes two limitations of the current diagnostic standard. The first limitation is the low sensitivity of the clinical diagnostic model, due to the progressive onset and the high variability of the syndrome. The second limitation is the unclear role of genetic testing. As genetic testing becomes more widely available, genetic diagnosis preceding clinical diagnosis will become more common, leading to a diagnostic conundrum. We propose an update of the diagnostic model. A less strict application in the presence of confirmed genetic mutations should be applied, as this could facilitate earlier diagnosis and intervention. This is important because therapeutic agents are being developed that could have a significant impact on quality of life and prognosis.<\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n \n \n Due to the low prevalence, the significant inter-and intrafamilial variation, and the slowly evolving phenotype, monogenic forms of obesity such as Bardet\u2013Biedl syndrome are difficult to diagnose. Despite advances in the understanding of the presentation, pathophysiology and access to accurate genetic characterisation, a substantial number of diagnoses are still made by ophthalmology, as recognition of BBS in other departments of medicine, remains limited.<\/jats:p>\n <\/jats:list-item>\n \n Clinical diagnosis of BBS is based on Beales\u2019 modified diagnostic criteria which require the presence of four primary features or three primary features plus two secondary features. This model has its limitations. Due to the progressive onset of clinical symptoms, patients generally do not meet the diagnostic criteria early in life, leading to a delay in diagnosis. In addition, the role of genetic testing remains controversial. However, as it becomes more widely available, genetic diagnosis may precede a full clinical diagnosis.<\/jats:p>\n <\/jats:list-item>\n \n BBS has an impact on the quality of life and prognosis of both the patient and the family. Obesity management strategies are an important part of the multidisciplinary approach, as there is no cure available. Setmelanotide has shown promising results in a phase 3 trial, but its effect in clinical practice remains unproven.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-23-0055","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T06:07:45Z","timestamp":1700806065000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":7,"title":["A diagnostic conundrum in Bardet\u2013Biedl syndrome: when genetic diagnosis precedes clinical diagnosis"],"prefix":"10.1530","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3339-237X","authenticated-orcid":true,"given":"Nele","family":"Van Roy","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvester","family":"Heerwegh","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dashty","family":"Husein","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke","family":"Ruys","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Vitaz, Sint-Niklaas, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Coremans","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Advances in Genomics and Genetics","first-page":"1","article-title":"Obesity\u2013Are we continuing to play the genetic \u201cblame game\u201d","volume":"6","author":"Radha","year":"2016","unstructured":"Radha V & Mohan V. Obesity\u2013Are we continuing to play the genetic \u201cblame game\u201d. Advances in Genomics and Genetics201661\u201323. (https:\/\/doi.org\/10.2147\/AGG.S52018)"},{"key":"bib2","series-title":"Therapeutics and Clinical Risk Management","first-page":"115","article-title":"Bardet-Biedl syndrome: current perspectives and clinical outlook","volume":"19","author":"Melluso","year":"2023","unstructured":"Melluso ASecondulfo FCapolongo GCapasso G & Zacchia M. Bardet-Biedl syndrome: current perspectives and clinical outlook. Therapeutics and Clinical Risk Management202319115\u2013132. (https:\/\/doi.org\/10.2147\/TCRM.S338653)"},{"key":"bib3","series-title":"Journal of Medical Genetics","first-page":"437","article-title":"New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey","volume":"36","author":"Beales","year":"1999","unstructured":"Beales PLElcioglu NWoolf ASParker D & Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. Journal of Medical Genetics199936437\u2013446. (https:\/\/doi.org\/10.1136\/jmg.36.6.437)"},{"key":"bib4","series-title":"American Journal of Medical Genetics. Part A","first-page":"352","article-title":"Clinical and genetic epidemiology of Bardet\u2013Biedl syndrome in newfoundland: a 22\u2010year prospective, population\u2010based, cohort study","volume":"132","author":"Moore","year":"2005","unstructured":"Moore SJGreen JSFan YBhogal AKDicks EFernandez BAStefanelli MMurphy CCramer BC & Dean JC. Clinical and genetic epidemiology of Bardet\u2013Biedl syndrome in newfoundland: a 22\u2010year prospective, population\u2010based, cohort study. American Journal of Medical Genetics. Part A2005132352\u2013360. (https:\/\/doi.org\/10.1002\/ajmg.a.30406)"},{"key":"bib5","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1834","article-title":"The endocrine and metabolic characteristics of a large Bardet-Biedl syndrome clinic population","volume":"103","author":"Mujahid","year":"2018","unstructured":"Mujahid SHunt KFCheah YSForsythe EHazlehurst JMSparks KMohammed STomlinson JWAmiel SACarroll PV, The endocrine and metabolic characteristics of a large Bardet-Biedl syndrome clinic population. Journal of Clinical Endocrinology and Metabolism20181031834\u20131841. (https:\/\/doi.org\/10.1210\/jc.2017-01459)"},{"key":"bib6","series-title":"Lancet. Diabetes and Endocrinology","first-page":"859","article-title":"Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and alstr\u00f6m syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period","volume":"10","author":"Haqq","year":"2022","unstructured":"Haqq AMChung WKDollfus HHaws RMMartos-Moreno G\u00c1Poitou CYanovski JAMittleman RSYuan GForsythe E, Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and alstr\u00f6m syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet. Diabetes and Endocrinology202210859\u2013868. (https:\/\/doi.org\/10.1016\/S2213-8587(2200277-7)"},{"key":"bib7","series-title":"Clinical Obesity","first-page":"e12546","article-title":"Weight loss with glucagon-like peptide-1 receptor agonists in Bardet-Biedl syndrome","volume":"12","author":"Ganawa","year":"2022","unstructured":"Ganawa SSanthosh SHParry L & Syed AA. Weight loss with glucagon-like peptide-1 receptor agonists in Bardet-Biedl syndrome. Clinical Obesity202212e12546. (https:\/\/doi.org\/10.1111\/cob.12546)"},{"key":"bib8","series-title":"Nature Genetics","first-page":"392","article-title":"Linkage of Bardet-Biedl syndrome to chromosome 16q and evidence for non-allelic genetic heterogeneity","volume":"5","author":"Kwitek-Black","year":"1993","unstructured":"Kwitek-Black AECarmi RDuyk GMBuetow KHElbedour KParvari RYandava CNStone EM & Sheffield VC. Linkage of Bardet-Biedl syndrome to chromosome 16q and evidence for non-allelic genetic heterogeneity. Nature Genetics19935392\u2013396. (https:\/\/doi.org\/10.1038\/ng1293-392)"},{"key":"bib9","series-title":"BMC Medical Genetics","first-page":"10","article-title":"Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants","volume":"18","author":"Esposito","year":"2017","unstructured":"Esposito GTesta FZacchia MCrispo AADi Iorio VCapolongo GRinaldi LD'Antonio MFioretti TIadicicco P, Genetic characterization of Italian patients with Bardet-Biedl syndrome and correlation to ocular, renal and audio-vestibular phenotype: identification of eleven novel pathogenic sequence variants. BMC Medical Genetics20171810. 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