Bardet Biedl Syndrome

Management of Bardet-Biedl Syndrome A Clinical Guideline

Bardet-Biedl Syndrome Guideline Development Group Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl

- Euro-WABB is supported by the European Commission under the Health Programme Framework (Agreement Number: 2010 12 05) 1 Version 14 April 28th 2014

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Contents Introduction 3 … to Bardet-Biedl Syndrome (BBS) 3 … to the Bardet-Biedl Syndrome Guideline Development project 3 … to the Bardet-Biedl Syndrome Clinical Management Guidelines 3 Diagnosis of Bardet-Biedl Syndrome 4 … Diagnosis and clinical features of BBS 4 … Baseline Investigations in BBS 5 Recommendations for the Management of Bardet-Biedl Syndrome 6 … Sensory involvement 6 … Visual assessment : Retinal dystrophy 6 … Hearing assessment : Conductive or sensorineural hearing loss 6 … Renal involvement 7

… Metabolism and Endocrine system 8 … Obesity 8 … Insulin resistance/type 2 diabetes mellitus 9

… Neuro-cognitive involvement 10 … Orthopaedic and dysmorphic features 11 … Genetics 12 Bibliography 13

Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl Acknowledgements 15 - Information to patients 16

2 Bardet

Introduction...

… to Bardet-Biedl Syndrome Bardet-Biedl syndrome (BBS) is a rare disease with prevalence of about 1:100,000 (North America). BBS is characterized by multi-system involvement: rod-cone dystrophy (>90%), truncal obesity (72%), postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, renal abnormalities, and variable complex female genitourinary malformations. The visual prognosis for children with BBS is poor with mean age of legal blindness of 15 years. Significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties, but only a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality. The diagnosis of BBS is established by clinical findings. Multiple genes are known to be associated with BBS: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15) SDCCAG8 (BBS16) LZTFL1 (BBS17), and BBTP1 (BBS18). BBS is typically inherited in an autosomal recessive manner, but up to 15% of patients do not have identifiable mutations in known genes. Both interfamilial and intrafamilial phenotypic variability exists. Carrier testing and prenatal testing are possible if the disease-causing mutations

Management Guidelines Management in a family are known.

… to the Bardet-Biedl syndrome guideline project The guidelines have been developed by referring physicians and geneticists involved in the EURO-WABB project, according to the DYSCERNE guideline development process (www.dyscerne.org.dysc.home/). The experts who participated to the guideline development are listed on page 15.

Clinical … to the Bardet-Biedl syndrome clinical management guidelines What are the aims of the guidelines ? The guidelines aim to provide recommendations for the diagnosis, management and follow-up of patients with BBS. As it is a multisystemic disorder, BBS patients may require various tests, screening and multidisciplinary interventions at different stages of their lives. These recommendations aim to support high quality care for people with BBS in a format that is accessible to anybody who is involved in the care of these patients. Note that transition is a process which includes the event of transfer from childrens’ to adult services and needs to attend to the medical, psychosocial, and educational/vocational needs of the young person and his/her parents/carers. Care needs to be provided that includes attention to transition needs.

How they are organised ? Syndrome Syndrome The guidelines are divided into - clinical features and diagnostic criteria - baseline investigations - any recommended tests, that are listed and organised into specific groups corresponding to the different symptoms and

Biedl affected organs. Any recommendations that are specifically addressed either to children or to adult patients are specified. - A list of references starts on page 16, organised according to the different sections of the guidelines. Additionally, there is a list of useful contacts for patients and families affected by BBS, on page 21.

Note: N=normal; ABNL= abnormal 3 Bardet

Diagnosis and clinical features of Bardet-Biedl Syndrome

Diagnostic criteria of BBS Beales et al [1999 and 2001] have suggested that the presence of four primary features or three primary features plus two secondary features is necessary for diagnosis:

Primary Features Secondary Features

Rod-cone dystrophy (76%, 72%) Speech delay/disorder (2%, 2%) Postaxial polydactyly (80%, 79%) Developmental delay (9%, 5%) Truncal obesity (80%, 77%) Behavioral abnormalities (9%, 7%) Learning disabilities (24%, 30%) Eye abnormalities include strabismus, cataracts, and astigmatism Hypogonadism in males (17%, 26%) or genital abnormalities in females Brachydactyly/syndactyly (4%, 3%) (4%, 4%) Ataxia/poor coordination/imbalance (0%, 0%) Renal disease (9%, 10%) Mild hypertonia (especially lower limbs) (0%, 0%) Diabetes mellitus (4%, 6%) Orodental abnormalities (2%, 2%) Cardiovascular anomalies (6%, 10%) Hepatic involvement (0%, 5%) Craniofacial dysmorphism (0%, 1%) Hirschsprung disease (2%, 1%) Anosmia (0%, 0%)

Note: The diagnosis is established in individuals of all ages in whom two pathological mutations in the same BBS gene are identified. A few cases have been reported of tri-allelic inheritance.

Percentages in parentheses after features are based on prevalence in a cohort of 96 BBS patients (46 with Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl

- molecular genetic diagnosis) participating in the EURO-WABB registry (% in those with genetic diagnosis, % overall).

4 Bardet

Recommended baseline investigations in Bardet-Biedl Syndrome

Clinical Features of BBS Baseline investigations

Rod-cone dystrophy Ophthalmologic evaluation, electroretinogram, visual field testing, fundus examination, ERG, OCT. Orthopedic abnormalities Note postaxial polydactyly, facial dysmorphism, dental abnormalities and pes planus with varus deformity and frequent genu valgum on physical examination

Obesity Measurement of weight and height; calculation of body mass index (BMI) and waist-hip ratio Hypogonadism or genital Examination of the external genitalia in both sexes. abnormalities

Insulin resistance/ Fasting plasma glucose, even in infancy; glucose tolerance test (GTT) > age 6years diabetes mellitus Fasting plasma insulin concentration, as hyperinsulinemia may be present from infancy

Hyperlipidemia A fasting lipid profile, including triglycerides

Renal and Urologic Ask about urinary symptoms especially polyuria/polydipsia. Baseline blood pressure; disease 24-hour blood pressure monitoring Measurement of plasma urea and electrolytes, GFR, urine osmolarity. Renal ultrasound Neurologic symptoms Neurologic examination. Anosmia Consider smell identification test (e.g. PSIT) Respiratory Consider bronchiectasis Bilateral sensorineural Audiometry with auditory brain stem response (ABR) and otoacoustic emissions (OAE); hearing loss assessment for otitis media and conductive hearing loss

Cardiovascular Auscultation, ECG, Echocardiography anomalies Hepatic disease Measurement of plasma ALT, AST, and GGT concentration ; Liver ultrasonography

Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl Confirmation of BBS diagnosis -

Molecular Analysis Testing of genes known associated with BBS: BBS1, BBS2, ARL6 (BBS3), BBS4, 5 BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11),

BBS12, MKS1 (BBS13), and CEP290 (BBS14) +/- Mutations in WDPCP (BBS15) Bardet

Recommendations for the management of Bardet-Biedl Syndrome Sensory involvement

Visual assessment : Cone-rod dystrophy

At diagnosis Ophthalmologic assessment with visual acuity (nystagmus, strabismus, dark adaptation, refraction : in childhood astigmatism/high myopia) Visual field testing (peripheral loss initially) Fundus examination (Atypical pigmentary retinal dystrophy with early macular involvement ) Electroretinography (ERG) testing indicated from 4 years of age OCT scan if suspected macular edema, VEP for differential diagnosis

Follow up Yearly eye examination: - Visual acuity (loss of 3 degrees per year during adolescence, <20/200 by the 2nd to 3rd decade) - Visual field testing (typically abnormal by10y) - Fundus examination (Retinal photography for later comparison) - ERG - Screen for cataract, glaucoma and diabetic retinopathy as appropriate.

Correction of refractive error (myopia, astigmatism), tinted glasses (if photophobia). Cataract surgery if needed. Use of low vision aids and mobility training (magnifying glasses, digital systems, voice systems). Educational planning. Consider disrupted sleep patterns, nocturnal apnoea and sleep studies if indicated. Hearing assessment: Conductive and/or sensorineural hearing loss

At diagnosis Audiogram / audiometry, tympanogram

Auditory evoked potentials

Follow up Yearly examination : audiometry Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl

- Detect glue ear (acute and chronic otitis media): can lead to an additional conductive hearing loss

Prompt treatment for acute and chronic otitis media

Management in standard way by a specialist (myringotomy tubes and/or hearing aids) 6 Bardet BardetWolfram-Biedl Syndrome Syndrome Clinical Clinical Management Management Guidelines Guidelines Recommendations themanagement for of Renal malformations and abnormal renal function leading to end stage stage renal end todisease leading (ESRD) abnormal Renal renal functionmalformations and diagnosis At Follow ------Complications Structural renal abnormalities

Nephrogenic renal Recurrent colic and urinarytract Vesico Renal calculi Hypertension acidosis,Renal tubular Decreased urine

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diabetes

reflux reflux

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transplantation - - - to Referral a - haematuria - - tract glomerular disease, detrusor >lowermalformations, malformations urinary diffuse unilateralcortical scarring, agenesis, dysplasia,renal disease, tubularcystic upper tract - - - -

Progressive Yearlyanalysisearlyfor morning urine albumin Regular monitoring Follow Yearly Bladder and renal ultrasound examination ( Measurement of plasma Baselineblood pressure Ask aboutof symptoms Yearlym capacity

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assessment creatinine creatinine creatinine blood pressure +/ , polyuria,and polydipsia , urea, electrolytes,GFR. ; 24 , , urea and - urea, electrolytesand GFR hour blood pressure monitoring calyceal

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Recommendations for the management of Bardet-Biedl Syndrome Metabolism and Endocrine System

Truncal obesity From the first year of life (usually normal birth weight) : - Clinical examination (Note relative hyperphagia, excessive weight gain, levels of physical activity) - Calculation of body mass index (BMI) : Obesity if > 95thcentile for age and sex (BMI>30 in adults)

Follow up - Annually measurement of weight and height; calculation of BMI (plot on growth charts). - Dietary evaluation especially if obesity is present -Education and dietary measures (healthy, reduced calorie diet), regular exercise (allowing for visual impairment) and lifestyle measures from an early age.

Obstructive sleep -Annual screening for sleep apnoea using a questionnaire; overnight oximetry if abnormal apnoea -Nocturnal CPAP therapy. Consider bronchiectasis Hypogonadotropic - Examination of the genitalia in both sexes (hypogonadism common in males) hypogonadism - Hormone levels : testosterone (or oestradiol+prolactin), gonadotropins FSH and LH, inhibin B -Pelvic ultrasound examination (females). Complex genitourinary malformations can occur

-Surgical correction, hormone replacement therapy

Hypercholesterolemia - Yearly fasting lipid profile, including triglycerides -Annual liver function tests

Hypothyroidism - Thyroid function testing: at diagnosis, then annually. Treatment with thyroxine

Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl -

Wolfram Syndrome Clinical Management Guidelines Management Clinical Syndrome Wolfram Bardet BardetWolfram-Biedl Syndrome Syndrome Clinical Clinical Management Management Guidelines Guidelines in adolescence up Follow diagnosis At Recommendations themanagement for of

Insulin Insulin resistance ------

Note Annual fasting Promotion of healthy Oral Fasting plasma glucose ( A Fasting plasma glycated glucose tolerance test (OGTT) glucose tolerance after test age(OGTT) acanthosis

hemoglobin equal to orgreater than 6.5% a is sufficient for the criterion diagnosis of diabetes plasma plasma Casual

nigricans insulinconcentration, as Endocrine Endocrine System Fasting (at least Plasma Glucose 8 hours) ≥ (FPG) 7.0 2 hour 11.1PG ≥ eating, postprandial blood glucose glucose FPG)

(indication of insulin resistance/diabetes mellitus) Glycated

( polyuria physical activity and lifestyle within limits of physicalandactivityimpairment of visuallimits lifestylewithin /

Diagnostic criteria criteria Diagnostic diabetes of Type 2Diabetes Mellitus

hemoglobin equal to or , polydipsia mmol hyperinsulinemia /L in a 75 12 years

and unexplained weightloss) ≥ ≥ 11.1 Or Or Or

g oral glucose tolerance Bardet

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BardetWolfram-Biedl Syndrome Syndrome Clinical Clinical Management Management Guidelines Guidelines Recommendations themanagement for of Management Management assessment Mental impairment Cognitive impairment Speech ++ delay Developmental

health

by neurolodevelopmental - behavior ------incoordination) - - and(gross andyears),motor fine) skills (interactiveto psychosocialplay/ability skills recognizesocial cues). - Neuropsychologicaltesting adapted to Early Ask Ask about anxiety psychologyEarlyintervention,clinical assessment of special educational needs Consider Speech therapyassessment Assessment languageof skills: speech (intelligibleand sentence formation Consider

speech speech therapyshould be offered at the first , autistic Neuro videofluoroscopy referral to referral healthpsychology/cognitivepsychiatric services/clinical

spectrum , emotional emotional immaturity, , Annual assessments Annualfor children - cognitive cognitive involvement

paediatricians

disorder

and palatalarticulationstudies (pharyngeal and/or laryngealmuscles

, psychotic age and low anger outbursts

episodes clinical psychologistsclinical signs signs vision

of of speech delayand/or impairment. Bardet , and/or disinhibition

educational

- , Biedl depression maybe delayed

evaluation behaviour

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therapy

until age four compulsive compulsive

BardetWolfram-Biedl Syndrome Syndrome Clinical Clinical Management Management Guidelines Guidelines Recommendations themanagement for of Follow up abnormalities Dental dysmorphism Craniofacial abnormalities Orthopedic polydactyly Postaxial

Orthopedic Orthopedic and Dysmorphic features hypoplasia balding, ears, large short and narrow Craniofacial defects include If abnormal, consider physiotherapy,correction surgical Follow referral Orthotic Surgicalremoval - - minimus - Examination of allfour limbs Antibiotic prophylaxisfor surgical and dental procedures for individuals Dental extractions are appropriate as required for dental crowding Dental evaluation to assess for hygiene,dental crowding,and up Followa bydentist : Note dental abnormalities ( nose and upper lip,

Partial Brachydactyly Additionaldigitson the ulnar side of the hand and on the fibular side of the up examination for: syndactyly , insertional , nasal shortening/reduced ,

of of , fifth , midfacial accessorydigits polydactyly

- finger dentalcrowding, scoliosis, scoliosis, brachycephaly

for for detection of: hypoplasia clinodactyly

on hands and feet.

genu palpebral bulbosity , and mild , valga , prominent prominent "sandal gap" , betweenthe 1st and 2nd toes. , hypodontia macrocephaly

fissures, longfissures, shallow at the nasal tip, upwardrelativedisplacement of the , vara retrognathia Bardet

, pes , small dentalsmall and roots, , high

planus bitemporal hypodontia

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deformity. foot; foot; presence of post , nasal bridge cardiopathy

- arched arched palate) 11 .

Recommendations for the management of Bardet-Biedl Syndrome Genetics

Locus heterogeneity with 17 genes known to be responsible for BBS: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14),SDCCAG8 (BBS16) and LZTFL1 (BBS17) +/- Mutations in WDPCP (BBS15) (no evidence of pathogenicity)

Molecular Genetic To confirm the diagnosis in a proband : diagnosis of BBS relies on clinical findings and family history testing Molecular analysis: - Screening for the M390R mutation in BBS1 (10-45% cases) - Sequence analysis for genes BBS1, BBS2, BBS 6, BBS10 and BBS12 (responsible for 84% of published alleles) - Sequence analysis of the rest of known BBS-related genes and for WDPCP. - Deletion/duplication analysis for BBS4, BBS5, BBS7, and BBS9, and also for genes in which no deletions or duplications have been reported (TRIM32, BBS1, BBS2, ARL6, MKKS, TTC8, Genetic BBS10, BBS12, and MKS1). counselling 1 or 2 mutated alleles : perform mutation screening in parents of index case and in affected relatives Approximately 15% of persons with BBS do not have identified mutations - Information about recurrence risk to parents (25%), to young adult patients who are affected, are carriers, or are at risk of being carriers and extended family members (++ before pregnancy). BBS is usually inherited in an autosomal recessive manner (multiallelic inheritance: fewer than 10%) - Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family. Note: Carriers (heterozygotes) are asymptomatic (autosomal recessive disorder). Prenatal Diagnosis - Available only for families in which the disease-causing mutation has been identified For pregnancies at increased risk for BBS (example : 25% recurrence risk for parents) By analysis of DNA extracted from fetal cells obtained by amniocentesis or chorionic villus sampling. - Ultrasound examination in pregnancies at increased risk : to detect anomalies such as postaxial polydactyly and renal cysts (enlarged hyperechoic kidneys without corticomedullary differentiation should be considered recurrence of BBS). - Ultrasound examination in pregnancies not known to be at increased risk. When antenatal ultrasonography reveals large hyperechoic kidneys with loss of corticomedullary differentiation in the

presence of polydactyly a diagnosis of BBS or Meckel syndrome should be considered Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl

- Preimplantation To discuss with referral centres (may be available for families in which the disease-causing mutation Genetic Diagnosis has been identified). 12

Wolfram Syndrome Clinical Management Guidelines Management Clinical Syndrome Wolfram Bardet

Management of Bardet-Biedl Syndrome Bibliography

1- Visual impairment Azari AA, Aleman TS, Cideciyan AV, Schwartz SB, Windsor EA, Sumaroka A, Cheung AY, Steinberg JD, Roman AJ, Stone EM, Sheffield VC, Jacobson SG. Retinal disease expression in Bardet-Biedl syndrome-1 (BBS1) is a spectrum from maculopathy to retina-wide degeneration. Invest Ophthalmol Vis Sci. 2006;47:5004–10.

Héon E, Westall C, Carmi R, Elbedour K, Panton C, Mackeen L, Stone EM, Sheffield VC. Ocular phenotypes of three genetic variants of Bardet-Biedl syndrome. Am J Med Genet A. 2005;132A:283–7.

2- Hearing loss

Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 1999;36:437–46.

Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger DJ, Leitch CC, Chapple JP, Munro PM, Fisher S, Tan PL, Phillips HM, Leroux MR, Henderson DJ, Murdoch JN, Copp AJ, Eliot MM, Lupski JR, Kemp DT, Dollfus H, Tada M, Katsanis N, Forge A, Beales PL. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet. 2005;37:1135–40.

3- Orthopedic and dysmorphic

Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 1999;36:437–46.

Ramirez N, Marrero L, Carlo S, Cornier AS. Orthopaedic manifestations of Bardet-Biedl syndrome. J Pediatr Orthop. 2004;24:92–6.

Lorda-Sanchez I, Ayuso C, Sanz R, Ibañez A. Does Bardet-Biedl syndrome have a characteristic face? J Med Genet. 2001;38:E14.

Moore SJ, Green JS, Fan Y, Bhogal AK, Dicks E, Fernandez BA, Stefanelli M, Murphy C, Cramer BC, Dean JC, Beales PL,

Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl Katsanis N, Bassett AS, Davidson WS, Parfrey PS. Clinical and genetic epidemiology of Bardet-Biedl syndrome in - Newfoundland: a 22-year prospective, population-based, cohort study. Am J Med Genet A. 2005;132:352–60.

13 Bardet BardetWolfram-Biedl Syndrome Syndrome Clinical Clinical Management Management Guidelines Guidelines 2002;61:1925 PS,Parfrey Davidson Green and Clinical WS, JS. genetic epidemiologyof inheritedrenal disease in Newfoundland. KidneyInt. of a populationsurvey. Med Genet.J 1999;36:437 Beales PL,for improved FA. New diagnosisElcioglucriteria AS,D, Flinter of N, Woolf Parker Bardet syndrome. NephrolChild Urol.1990;10:109 Barakat ArianasAD,AJ, Focal glomerulonephritis ButlerMG. sclerosing in P, aLaurence Glick childwith Nephrologie.1987;8:189 B, nephropathy François CahenP, Dumontel Calemard E, J, C. Glomerular Trolliet GillyR, in the Bardet of Bardet Parfrey O’Dea D, PS,BC, J. Harnett Hefferton Green JD, D, Cramer The importance of renalthe impairment in natural history 5 Pediatr. 2003;45:273 A.M, S,S,Cetin BardetUguralp Demircan Sigirci Genet. 1997;69:220. Mehrotra N, Taub Hydrometrocolposas S,RF. Covert aneonatal manifestation of the Bardet of a populationsurvey. Med Genet.J 1999;36:437 Beales PL,for improved FA. New diagnosisElcioglucriteria AS,D, Flinter of N, Woolf Parker Bardet Int J Obes MetabRelat Disord.2003;27:1319 Grace C, BealesC, Jebb P, Summerbell A,D, Kopelman SA, Parker Wright P. Energyinmetabolism Newfoundland: a 22 Katsanis N,Bassett AS, DavidsonPS.Parfrey WS, Moore Green SJ, Fan JS, BhogalY, AK,E, Fernandez Dicks BC,BA, Dean Beales JC, Stefanelli Cramer PL,M, MurphyC, 4

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Bibliography - - based, cohort study.J Genet Am Med A. 2005;132:352 – –

Biedl associated syndrome with vaginalatresia: a case report. Turk J 46. 46. Clinical and Clinicalgenetic epidemiology of Bardet

– 83.

- Biedl SyndromeBiedl

- Biedl syndrome. Am syndrome. Biedl J Am Med - Biedlsyndrome in

- - Biedl results syndrome: Biedl results syndrome: Bardet - - Biedlsyndrome. – Moon 60. - Biedlsyndrome.

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BardetWolfram-Biedl Syndrome Syndrome Clinical Clinical Management Management Guidelines Guidelines Acknowledgements Bergmann Bergmann C Beales Barrett T Ayme S guideline: this to contributed kindlypeople following The package (work V lead Prof package ofwork outcome the EURO an 4 these is ofguidelines ofdevelopmentThe Valverde Vialettes Tsaloumas Tomlinson J Tillmann Sinnott Rohayem Richens Paquis Nunes Mohammed S Mlynarski Milford D McGee M McCafferty S Maffei P Lopez Kershaw M Hulton Hamel C Foggensteiner Denniston Chaussenot

de de Heredia M -

V S P R Flucklinger

V B

Paquis

- Flucklinger University Universit Queen Universityof Birmingham, UK Universityof Tartu, Universityof Glasgow, Universityof NIHR Universityof Nice, France IDIBELL, Spain Guy’s Hospital, London, UK Medical University Lodz, Poland of Birmingham Children’s Hospital, UK Birmingham Children’s Hospital, UK Universityof Glasgow, UK Universityof CIBERER, Spain Birmingham Children’s Hospital, Birmingham, UK Birmingham Children’s Hospital, UK University of Montpellier, France Queen Elizabeth Hospital, Birmingham, UK Queen Elizabeth Hospital, Birmingham, UK Universityof Nice, France Bioscientia Child Institute of Health, University College London, UK Universityof Birmingham, UK CNRS, France Wellcome

Elizabeth Elizabeth )

y of of yMarseille, France

of of Vigo, Spain , Germany Münster, Germany Padova

Clinical Research Facility, Birmingham, UK Hospital

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, Birmingham, UK

- WABBproject

Information for patients

Sources of information and support

The groups listed below are useful sources of support and information

•Association BBS – Association Bardet Biedl Contact : M. Bertrand LASBLEIS - Tél. 33 (0)2 43 23 56 67 - Email. [email protected]

•Laurence-Moon-Bardet-Biedl society: www.lmbbs.org.uk The Society supports over 400 families and communicates with over 150 health professionals involved in their care.

• Bardet-Biedl Syndrome Family Association (USA): http://www.bardetbiedl.org/ • Supports US based families and their carers

• Pro Retina Deutschland e.V. - BBS-patient group: www.pro-retina.de/bbs Contact partner: Franziska Kellermann, email: [email protected]

•Orphanet (www.orpha.net) Orphanet is an online database of rare diseases and related services provided through Europe. It contains information on over 5 000 conditions and lists specialised clinics, diagnostic tests, patient and organizations, research projects and clinical trials

•OMIM (http://www.omim.org/) OMIM is a comprehensive, authoritative compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and the entries contain copious links to other genetics resources.

• RareConnect (https://www.rareconnect.org/en) RareConnect was created by EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders) to provide a safe space where individuals and families affected by rare diseases can connect with each other, share vital experiences, and find helpful information and resources

Biedl Syndrome Clinical Management Guidelines Management Clinical Syndrome Biedl

- • Gene Reviews – Bardet Biedl syndrome http://www.ncbi.nlm.nih.gov/books/NBK163

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