Monitoring and Management of Bardet-Biedl Syndrome: What the Multi-Disciplinary Team Can Do

Figures & data

Table 1 Criteria for Diagnosis of Bardet-Biedl Syndrome

Major Features	Minor Features	Criteria for Diagnosis
Rod-cone dystrophy Polydactyly Central obesity Hypogonadotropic hypogonadism and/or genitourinary anomalies Renal anomalies Cognitive impairment	Speech delay Developmental delay Diabetes mellitus Dental anomalies Congenital heart disease Brachydactyly/syndactyly Ataxia/poor coordination Anosmia/hyposmia	Four major features Three major features and two minor features

Table 2 Genes and Proteins Involved in Bardet-Biedl Syndrome

No	Gene (Previous/Alias Symbol)	Approved Name (Previous/Alternative Name)	Chromosomal Location	Protein – Recommended Name (Previous/Alternative Name)
1	BBS1 (FLJ23590)	Bardet-Biedl syndrome 1	11q13.2	Bardet-Biedl syndrome 1 protein (BBS2-like protein 2)
2	BBS2 (BBS)	Bardet-Biedl syndrome 2	16q13	Bardet-Biedl syndrome 2 protein
3	ARL6 (BBS3; RP55)	ADP ribosylation factor like GTPase 6 (ADP-ribosylation factor-like 6)	3q11.2	ADP-ribosylation factor-like protein 6
4	BBS4	Bardet-Biedl syndrome 4	15q24.1	Bardet-Biedl syndrome 4 protein
5	BBS5 (DKFZp762I194)	Bardet-Biedl syndrome 5	2q31.1	Bardet-Biedl syndrome 5 protein
6	MKKS (BBS6)	MKKS centrosomal shuttling protein (McKusick-Kaufman syndrome)	20p12.2	McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin
7	BBS7 (FLJ10715; BBS2L1)	Bardet-Biedl syndrome 7	4q27	Bardet-Biedl syndrome 7 protein
8	TTC8 (BBS8; RP51)	Tetratricopeptide repeat domain 8	14q31.3	Tetratricopeptide repeat protein 8
9	BBS9 (B1; PTHB1)	Bardet-Biedl syndrome 9 (parathyroid hormone responsive B1 gene)	7p14.3	Protein PTHB1 (Bardet-Biedl syndrome 9 protein; Parathyroid hormone-responsive B1 gene protein)
10	BBS10 (C12orf58; FLJ23560)	Bardet-Biedl syndrome 10 (chromosome 12 open reading frame 58)	12q21.2	Bardet-Biedl syndrome 10 protein
11	TRIM32 (LGMD2H)	Tripartite motif containing 32 (limb girdle muscular dystrophy 2H (autosomal recessive); tripartite motif-containing 32; E3 ubiquitin-protein ligase TRIM32)	9q33.1	E3 ubiquitin-protein ligase TRIM32 (72 kDa Tat-interacting protein; RING-type E3 ubiquitin transferase TRIM32 Curated; Tripartite motif-containing protein 32; Zinc finger protein HT2A)
12	BBS12 (C4orf24; FLJ35630; FLJ41559)	Bardet-Biedl syndrome 12 (chromosome 4 open reading frame 24)	4q27	Bardet-Biedl syndrome 12 protein
13	MKS1 (MKS; FLJ20345; POC12; BBS13)	MKS transition zone complex subunit 1	17q22	Meckel syndrome type 1 protein (Meckel syndrome, type 1; POC12 centriolar protein homolog (Chlamydomonas))
14	CEP290 (KIAA0373; FLJ13615; 3H11Ag; rd16; NPHP6; JBTS5; SLSN6; LCA10; MKS4; BBS14; CT87; POC3)	centrosomal protein 290 (centrosomal protein 290kDa; Joubert syndrome 5; nephrocystin-6; cancer/testis antigen 87; POC3 centriolar protein homolog (Chlamydomonas); Meckel syndrome, type 4; Bardet-Biedl syndrome 14)	12q21.32	Centrosomal protein of 290 kDa (Cep290; Bardet-Biedl syndrome 14 protein; Cancer/testis antigen 87 (CT87); Nephrocystin-6; Tumor antigen se2-2)
15	WDPCP (C2orf86; hFrtz; fritz; BBS15; CPLANE5)	WD repeat containing planar cell polarity effector (chromosome 2 open reading frame 86; ciliogenesis and planar polarity effector complex subunit 5)	2p15	WD repeat-containing and planar cell polarity effector protein fritz homolog (hFRTZ) (Bardet-Biedl syndrome 15 protein; WD repeat-containing and planar cell polarity effector protein)
16	SDCCAG8 (NY-CO-8; CCCAP; SLSN7; NPHP10; BBS16)	SHH signalling and ciliogenesis regulator SDCCAG8 (serologically defined colon cancer antigen 8; centrosomal colon cancer autoantigen protein; Bardet-Biedl syndrome 16; nephrocystin 10; Senior-Loken syndrome 7)	1q43-q44	Serologically defined colon cancer antigen 8 (Antigen NY-CO-8; Centrosomal colon cancer autoantigen protein (hCCCAP))
17	LZTFL1 (BBS17)	leucine zipper transcription factor like 1 (leucine zipper transcription factor-like 1)	3p21.31	Leucine zipper transcription factor-like protein 1
18	BBIP1 (NCRNA00081; bA348N5; BBIP10; BBS18)	BBSome interacting protein 1 (non-protein coding RNA 81)	10q25.2	BBSome-interacting protein 1 (BBSome-interacting protein of 10 kDa)
19	IFT27 (RABL4; RAYL; BBS19; FAP156)	Intraflagellar transport 27 (RAB, member of RAS oncogene family-like 4; intraflagellar transport 27 homolog (Chlamydomonas))	22q12.3	Intraflagellar transport protein 27 homolog (Putative GTP-binding protein RAY-like; Rab-like protein 4)
20	IFT74 (CCDC2; CMG1; CMG-1; FLJ22621)	Intraflagellar transport 74 (coiled-coil domain containing 2; intraflagellar transport 74 homolog (Chlamydomonas); capillary morphogenesis protein 1)	9p21.2	Intraflagellar transport protein 74 homolog (Capillary morphogenesis gene 1 protein (CMG-1); Coiled-coil domain-containing protein 2)
21	CFAP418 (C8orf37; FLJ30600; CORD16; RP64; BBS21; FAP418; MOT25)	Chromosome 8 open reading frame 37 (chromosome 8 open reading frame 37; cone-rod dystrophy 16; Bardet-Biedl syndrome 21)	8q22.1	Cilia- and flagella-associated protein 418
22	CCDC28B (MGC1203; RP4-622L5.5)	Coiled-coil domain containing 28B	1p35.2	Coiled-coil domain-containing protein 28B
23	SCLT1 (hCAP-1A, FLJ30655)	Sodium channel and clathrin linker 1	4q28.2	Sodium channel and clathrin linker 1 (Sodium channel-associated protein 1)
24	NPHP1 (NPH1; JBTS4; SLSN1)	Nephrocystin 1 (nephronophthisis 1 (juvenile))	2q13	Nephrocystin-1 (Juvenile nephronophthisis 1 protein)
25	SCAPER (ZNF291; Zfp291)	S-phase cyclin A associated protein in the ER (zinc finger protein 291)	15q24.3	S phase cyclin A-associated protein in the endoplasmic reticulum (S phase cyclin A-associated protein in the ER) (Zinc finger protein 291)
26	IFT172 (SLB; wim; osm-1; NPHP17; BBS20)	Intraflagellar transport 172 (intraflagellar transport 172 homolog (Chlamydomonas); wimple homolog)	2p23.3	Intraflagellar transport protein 172 homolog

Note: Data from these studies.^7–10.

Figure 1 Pleiotropy and multidisciplinary management in Bardet-Biedl syndrome. Created with BioRender.com.

Table 3 Prevalence of Overweight and Obesity

Age	Normal Weight (No/ %)	Overweight (No/ %)	Obesity (No/ %)
<2 years old	53 (44.5%)	39 (32.8%)	27 (22.7%)
2–5 years old	42 (21.4%)	36 (18.4%)	118 (60.2%)
6–11 years old	13 (5.9%)	24 (10.9%)	184 (83.3%)
12–19 years old	17 (8.2%)	31 (14.9%)	160 (76.9%)

Note: Data from Pomeroy et al.²⁵

Table 4 The International Diabetes Federation Consensus Definition of Metabolic Syndrome in Children, Adolescents and Adults

Age Group	Obesity	Triglycerides	HDL-C	Blood Pressure	Glucose (mmol/L) or Known T2DM
10–16 years	≥90th percentile or adult cut-off if lower	≥1.7 mmol/L (≥150 mg/dL)	<1.03 mmol/L (<40 mg/dL)	Sistolic ≥130/ Diastolic ≥85 mmHg	≥5.6 mmol/L (100 mg/dL) (If≥5.6 mmol/L [or known T2DM] recommend an OGTT)
≥16 years	Central obesity*	≥1.7 mmol/L	<1.03mmol/L (<40 mg/dL) in males and <1.29mmol/L (<50mg/dL) in females, or specific treatment for these lipid abnormalities	Systolic >130 or diastolic >85mmHg, or treatment of previously diagnosed hypertension	Impaired fasting glycemia (IFG): fasting plasma glucose (FPG)=5.6 mmol/L (≥100 mg/dL), or previously diagnosed type 2 diabetes

Note: *Central obesity is defined as waist circumference ≥ 94 cm for European men and ≥ 80 cm for European woman; ethnicity specific values for other groups.

Abbreviations: HDL-C, high-density lipoprotein cholesterol; OGTT, oral glucose tolerance test; T2DM, Type 2 diabetes mellitus.

Pomeroy J, Krentz AD, Richardson JG, Berg RL, VanWormer JJ, Haws RM. Bardet‐Biedl syndrome: weight patterns and genetics in a rare obesity syndrome. Pediatr Obes. 2021;16(2):e12703. doi:10.1111/ijpo.12703

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