Diagnose BBS Earlier

Rate of diagnosis is improving, previously 40% of cases were incorrectly diagnosed1

BBS overview

Rare and devastating ciliopathies such as Bardet-Biedl Syndrome (BBS) have no curative treatment2 and is known to cause 16 severe or life-threatening medical conditions.3-5 BBS is the first disorder to be described as ciliopathic6 and has a prevalence of 1 in 100,000 In Europe and North America.7

Learning Difficulties

People with BBS are affected by learning difficulties with poor educational attainment.3

Behavioral problems range from outbursts of frustration and obsessive-compulsive behavior patterns to autism; and anxiety and depression. 3

Developmental Delay

The majority of people with BBS suffer developmental delay.3

Children showed a delay in walking by one year and speaking by two years and boys can be slow in passing through puberty.3,10

Ataxia/Poor Coordination

Many affected individuals suffer from a degree of clumsiness or signs of ataxia and poor coordination.3

Rod Cone Dystrophy

Rod cone dystrophy causes night blindness in children progressing to legal blindness in most people by early adulthood.3

Electroretinography may reveal changes to photoreceptors in children within the first two years, although significant changes are rarely visible before age five.3

Anosmia or Hyposmia

People with BBS experience a reduced sense of smell or the inability to smell.3

Dental Anomalies

Overcrowded teeth and/or a high-arched palate are most common; however, misaligned teeth (malocclusion), missing teeth (hypodontia), small roots or thin enamel also occurs.3

Speech Delay

People with BBS experience speech delay and children often do not develop intelligible speech before the age of four.3

Speech is often high-pitched and nasal sounding. Speech difficulties may be complicated by hearing loss.3

Post-axial polydactyly

People with BBS are born with additional digits outside their little fingers or toes. This may be the only obvious sign of the disorder at birth.3

Brachydactyly/Syndactyly

People with BBS often have short/webbed fingers or toes.3

Congenital Heart Disease

Cardiac abnormalities observed in people with BBS are highly variable.

Congenital heart disease includes atrial septal defect (ASD) or ventricular septal defect (VSD), a hole in the wall between the two upper or lower chambers, respectively, or left ventricular hypertrophy (LVH), the thickening of the heart’s muscular walls.3

Hypertension

Hypertension is a feature of BBS which puts additional strain on the heart and could increase the risk of heart attack, heart failure and sudden cardiac death.4

High Cholesterol

People with BBS report significantly increased levels of triglycerides and cholesterol which can lead to fat deposits and clogging of blood vessels.5

Kidney Disease

Renal abnormalities or malformations affect people with BBS and can be life-threatening due to the development of chronic kidney disease (CKD) which may progress to end-stage disease in some.3,9

Obesity

People with BBS develop obesity, often due to feelings of extreme hunger.3,5 Babies with a normal birth weight often develop obesity by 12 months and development of type 2 diabetes is common.3,8

Genital Anomalies

Low levels of sex hormones delay puberty or prevent genitalia from developing in people with BBS, causing infertility in men and genital malformations in women.3

Why diagnose earlier?

Children with ciliopathic symptoms generally experience a “rare disease odyssey,” where patients reported to have waited five to 30 years for the correct diagnosis, with the initial diagnosis being incorrect in 40% of cases.1,11

Earlier diagnoses reduce stress for children and their parents and enable BBS-induced medical conditions to be managed more effectively from the start.2,12

For example, children can potentially receive interdisciplinary streamlined care where seven specialists can be seen in a single visit and those with speech delays are responsive to speech therapy.3

Diagnostic Criteria

Diagnostic criteria published by Prof. Phil Beales can be used to diagnose BBS before genetic testing has been completed or if genetic testing does not reveal a mutation in a gene known to cause BBS.3

A minimum of four primary or three primary and two secondary features are required for a clinical diagnosis of BBS.3

Primary Features
Rod-cone Dystrophy
Rod-cone Dystrophy Icon
Polydactyly
Polydactyly Icon
Obesity
Obesity Icon
Genital Anomalies
Genital Anomalies Icon
Learning Difficulties
Learning Difficulties Icon
Secondary Features
Speech Delay
Speech Delay Icon
Developmental Delay
Developmental Delay Icon
Diabetes Mellitus
Diabetes Mellitus Icon
Dental Anomalies
Dental Anomalies Icon
Congenital Heart Disease
Congenital Heart Disease Icon
Brachydactyly/Syndactyly
Brachydactyly/Syndactyly Icon
Ataxia/Poor Coordination
Ataxia/Poor Coordination Icon
Anosmia/Hyposmia
Anosmia/Hyposmia Icon

Diagnosis

Use this decision tree to assess people with suspected BBS who do not fulfill the diagnostic criteria for BBS outlined above.3

If the full BBS phenotype is not expressed, are there at least two primary BBS features present based on the diagnostic criteria above?

Is your patient an adult or a child?

Phenotype may still be evolving

See full assessment criteria under management

Discuss with a clinical geneticist if a BBS diagnosis is likely

Differential diagnosis:
Assess whether your patient has one of these conditions:

  • Alstrom syndrome
  • Joubert syndrome
  • Senior-Loken syndrome
  • Leber Congenital Amaurosis

Management

Use this decision tree to help confirm a suspected BBS diagnosis and to manage people with clinically diagnosed BBS.3

Does your patient have at least four primary or three primary and two secondary features from the diagnostic criteria above?

Disease management

Confirm a possible diagnosis

Assessment

Annual assessment

  • Weight
  • Blood pressure
  • Renal, thyroid, liver function tests, glucose, lipid and sex hormone profile
  • Ophthalmology review
  • Endocrinology review
  • Electroretinography (ERG) test if >5 years of age

At least once and more often if required

  • Review by a clinical geneticist
  • DNA for molecular diagnostics
  • Nephrology review
  • Renal ultrasound (USS)
  • Dietetics review
  • Developmental and educational assessment
  • Hearing evaluation
  • Clinical psychology review

If required

  • Oral glucose tolerance test
  • Referral to speech therapy
  • Echocardiography / referral to cardiology
  • Referral to mental health services
  • Referral to orthodontist

PATIENT CASE STUDIES

5 year old male

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8 year old female

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32 year old female

Had worked as a supermarket checkout assistant. Recently made redundant following increasing difficulty seeing money being handed to her.

Genetic testing

While diagnostic criteria for BBS may seem straightforward, children with learning disabilities and weight management challenges who aren’t born with a congenital abnormality may be difficult to diagnose until vision loss symptoms present.13 Genetic testing can help confirm a BBS diagnosis in people with specific BBS mutations such as BBS1 and BBS10.13

Increased genetic testing, prenatal testing and newborn screening can facilitate earlier diagnoses, reducing stress for children and their parents and enabling BBS-induced medical conditions to be managed more effectively from the start.2,12

Since BBS is not currently included on newborn screening panels and genetic tests are not widely available,13 a referral to a clinical geneticist is recommended to confirm a BBS diagnosis.

References

1EURORDIS 2007. 2Forsythe E, et al. Front Pediatr. 2018;6:23. 3Forsythe E, et al. Eur J Hum Genet. 2013;21:8–13. 4Thadchanamoorthy V, et al. Cureus 2021;13:e12617. 5Mujahid S, et al. J Clin Endocrinol Metab. 2018;103:1834–41. 6Waters AM, et al. Pediatr Nephrol. 2011;26:1039–56. 7Suspitsin EN, Imyanitov EN. Mol Syndromol 2016;7:62–71. 8Tobin JL, et al. Pediatr Nephrol. 2007;22:926–36. 9Forsythe E, et al. J Am Soc Nephrol. 2017;28:963–70. 10Beales PL, et al. J Med Genet 1999;36:437–446. 11Policy Innovation Research Unit. 2015. 12Ashkinadze E, et al. Clin Genet. 2013;83:553–9. 13NORD. BBS. 2017.

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