Bardet-Biedl syndrome: symptoms, genetics, diagnosis and NHS care

Bardet-Biedl syndrome is a rare genetic condition that affects several body systems. BBS UK, the UK charity for the condition, says it is a multi-system disorder with a significant impact on quality of life that may be life-limiting. Because the presentation varies so much and the condition is rare, BBS UK notes that diagnosis can be delayed and local healthcare may be inadequate.

BBS is classed as a ciliopathy. BBS UK explains that mutations in BBS genes change proteins needed for the correct functioning of the primary cilium, a hair-like projection on the surface of cells. Many cell types rely on a working primary cilium, including the light-sensing cells of the retina and cells in the kidney. Other ciliopathies it lists include Alström syndrome, primary ciliary dyskinesia, polycystic kidney disease, some forms of retinitis pigmentosa, nephronophthisis, Joubert syndrome and Meckel syndrome.

BBS UK lists the features as rod-cone dystrophy, a progressive eye disorder that leads to blindness, characterised by tunnel vision and night blindness; obesity; renal abnormalities; developmental delay; speech and language difficulties; extra fingers and/or toes; and learning difficulties. Not all features are always present, and each can vary in severity and appearance.

People with the same gene mutation can look quite different. BBS UK gives the example that one person may have extra digits at birth while another with an identical mutation has none.

BBS UK explains that in most cases both parents carry one normal and one faulty recessive gene. They are carriers and are unaffected. A child has to inherit two faulty copies, one from each parent, so each pregnancy has a 1 in 4 chance of an affected child. If a newborn is not affected, there is a 2 in 3 chance that the child is a carrier.

To date (2020, per BBS UK), mutations in 22 BBS genes have been identified in 85% of patients, and more genes remain to be found. A quarter of patients have mutations in BBS1 and another quarter in BBS10. BBS UK estimates the carrier frequency for BBS1 and BBS10 at around 1 in 250, and says the risk of two carriers meeting increases if people marry close relatives.

BBS UK says that Beales and colleagues suggested that four primary features, or three primary features plus two secondary features, are needed for a clinical diagnosis of BBS. Genetic testing identifies the mutation in most patients, and knowledge of the mutations can provide the basis for carrier testing and prenatal screening.

BBS UK recommends that all patients with a suspected diagnosis of BBS should be referred to one of the NHS specialised clinics. A GP or hospital specialist who suspects BBS can arrange this referral.

Rod-cone dystrophy is one of the primary features. BBS UK describes it as a progressive eye disorder that leads to blindness, characterised by tunnel vision and night blindness. The sources used here do not give a timeline for sight loss, which varies between people.

Eye care is part of the specialist clinic: BBS UK lists an ophthalmologist among the team at each clinic.

NICE describes BBS as a debilitating rare genetic condition that causes hyperphagia, characterised by a feeling similar to starvation, which can lead to early onset severe obesity. Symptoms are managed with best supportive care, which includes dietary restrictions and lifestyle changes including exercise.

NICE guidance HST31 (published 22 May 2024) recommends setmelanotide (Imcivree) as an option for treating obesity and hyperphagia in genetically confirmed BBS in people aged 6 years and over, only if treatment starts between the ages of 6 and 17. People who start in that age range can carry on as adults until they need to stop. NICE says trials suggest setmelanotide may reduce weight and BMI and may improve hunger scores and quality of life in the short term, but that long-term effects are uncertain. The medicine is only recommended if the company provides it under the commercial arrangement.

Renal anomalies are a primary feature, and polyuria and polydipsia, diabetes mellitus, left ventricular hypertrophy and hepatic fibrosis are listed as secondary features. BBS UK says the NHS clinics are staffed by an ophthalmologist, nephrologist, dietician, clinical psychologist, geneticist, speech and language therapist and endocrinologist, which reflects the range of body systems involved.

Annual clinic visits are intended to ensure patients receive specialised attention, with a focus on diagnosis, early intervention and good health management. The sources used here do not give specific monitoring schedules.

BBS UK says Great Ormond Street Hospital, Guy's and St Thomas' Hospital in London, Birmingham Children's Hospital and the Queen Elizabeth Hospital Birmingham are commissioned by NHS England to provide multidisciplinary clinics for people with BBS. Each clinic aims to be a one-stop annual visit with the specialists listed above.

The children's clinics are at Great Ormond Street and Birmingham Children's Hospital, and the adult clinics at St Thomas' Hospital London and the Queen Elizabeth Hospital Birmingham. Referrals are allocated by the service leads according to location and other factors, and telemedicine appointments are also offered. BBS UK suggests bringing recent reports, preparing a list of questions, and, for children, completing a food diary before the appointment. Help with travel costs is available to people on means-tested benefits.

BBS UK says that where BBS is confirmed genetically, a carrier test is possible for at-risk adult relatives such as siblings. Where both parents are carriers of a change in the same gene, every pregnancy has a 1 in 4 risk. Options include prenatal testing (chorionic villus sampling or amniocentesis, with a small risk to the pregnancy), pre-implantation genetic diagnosis (PGD) via a clinician if criteria are met, which vary between NHS centres, or detailed scans through pregnancy, although features may be difficult to see before 20 weeks.

For people who have BBS and want children, the first step is for their partner to be tested for carrier status. BBS UK says that children of an affected parent will all be carriers but will not have the syndrome unless the other parent has a change in the same gene, in which case each child has a 50% chance of having it.

BBS is a long-term condition rather than an emergency, and the sources used here do not list emergency signs specific to it. Contact your GP or the specialist team for new or worsening symptoms, and use NHS 111 or 999 as for anyone else: for example, 999 for chest pain, severe breathing difficulty or collapse.

For a child or adult you are worried about between clinic appointments, use your GP, NHS 111 or 999 in the same way as for anyone else.

BBS UK is the only registered charity supporting people with BBS, their families and carers in the UK. It runs an advice service on health, education and social care, a clinics support service, a conference, service user groups and information booklets, and holds the Patient Information Forum tick for its health information.

The charity also encourages people to prepare for education needs; for example, for children it suggests letting the team know if you are preparing to apply for an Education, Health and Care Plan so they can help.