Bardet-Biedl syndrome is a genetically heterogeneous autosomal recessive ciliopathy caused by biallelic pathogenic variants in established BBS genes encoding the BBSome, its chaperonin-like assembly machinery, and closely related ciliary trafficking proteins. The core disease logic is failure of primary-cilium cargo trafficking, producing retinal degeneration, early-onset obesity with hyperphagia, postaxial polydactyly, and structurally and functionally abnormal kidneys.
name: Bardet-Biedl syndrome
creation_date: "2025-12-04T16:57:31Z"
updated_date: "2026-04-13T01:21:32Z"
category: Mendelian
description: >-
Bardet-Biedl syndrome is a genetically heterogeneous autosomal recessive
ciliopathy caused by biallelic pathogenic variants in established BBS genes
encoding the BBSome, its chaperonin-like assembly machinery, and closely
related ciliary trafficking proteins. The core disease logic is failure of
primary-cilium cargo trafficking, producing retinal degeneration, early-onset
obesity with hyperphagia, postaxial polydactyly, and structurally and
functionally abnormal kidneys.
disease_term:
preferred_term: Bardet-Biedl syndrome
term:
id: MONDO:0015229
label: Bardet-Biedl syndrome
classifications:
harrisons_chapter:
- classification_value: hereditary disease
mechanistic_category:
- classification_value: ciliopathy
parents:
- Syndromic Obesity
- Ciliopathy
synonyms:
- BBS
notes: >-
This entry is framed at the classic syndrome level rather than split into a
large number of gene-specific diseases. Gene-specific differences such as
relatively milder BBS1 disease and more severe BBS10 renal and ocular disease
are recorded as genotype-phenotype observations, while noncanonical
"BBS-like" phenocopies are not merged automatically into this file.
inheritance:
- name: Autosomal recessive inheritance
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
description: >-
Classic Bardet-Biedl syndrome is an autosomal recessive syndromic
ciliopathy.
evidence:
- reference: PMID:20876674
reference_title: "Bardet-Biedl syndrome: a study of the renal and cardiovascular phenotypes in a French cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy with a
wide spectrum of clinical features including obesity, retinitis pigmentosa,
polydactyly, mental retardation, hypogonadism, and renal abnormalities.
explanation: >-
This cohort abstract explicitly states autosomal recessive inheritance for
classic BBS.
prevalence:
- population: European populations
percentage: 1 in 160,000
notes: >-
Founder populations can be much more common; the same epidemiologic abstract
cites prevalence as high as 1 in 13,000 in Kuwaiti Bedouins and estimated
minimum prevalence of approximately 1 in 156,000 in Tunisia.
evidence:
- reference: PMID:22109794
reference_title: "Prevalence of Bardet-Biedl syndrome in Tunisia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The prevalence of BBS has been estimated in different populations, ranging
from 1 in 160,000 in European populations to 1 in 13,000 in Bedouins from
Kuwait.
explanation: >-
This epidemiologic study provides a commonly cited prevalence range for
BBS, including the European estimate used here.
genetic:
- name: BBS1
association: Pathogenic biallelic variants
gene_term:
preferred_term: BBS1
term:
id: hgnc:966
label: BBS1
frequency: one of the most prevalent BBS genes
notes: >-
BBS1 is a recurrent cause of classic BBS; the common p.M390R allele is
frequent in multiple cohorts and BBS1 disease can be milder than BBS10 in
some series.
evidence:
- reference: PMID:28143435
reference_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."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The most common mutated gene was BBS1 followed by BBS10.
explanation: >-
This Italian cohort identifies BBS1 as the most common gene in that
series.
- reference: PMID:35886001
reference_title: "Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and
by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5
(21 alleles) and BBS1 c.1169T>G;p.M390R (18 alleles).
explanation: >-
This independent cohort confirms BBS1 as one of the two dominant genotype
groups in contemporary clinical series.
- name: BBS10
association: Pathogenic biallelic variants
gene_term:
preferred_term: BBS10
term:
id: hgnc:26291
label: BBS10
frequency: one of the most prevalent BBS genes
notes: >-
BBS10 is a common cause of BBS and is associated with more severe renal and
ocular disease in some human cohorts.
evidence:
- reference: PMID:35886001
reference_title: "Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and
by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5
(21 alleles) and BBS1 c.1169T>G;p.M390R (18 alleles).
explanation: >-
This German cohort identifies BBS10 as the most common genotype in that
series.
- reference: PMID:28143435
reference_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."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BBS10 was associated with the worse outcome in terms of the renal, ocular
and audiovestibular phenotypes.
explanation: >-
This cohort supports recording BBS10 as a genotype associated with more
severe multisystem disease.
- reference: PMID:21209035
reference_title: "Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BBS1 (27%) and BBS10 (30%) mutations were the most prevalent.
explanation: >-
This metabolic cohort independently confirms BBS10 as one of the most
prevalent genotypes.
- name: Other established BBS genes
association: Pathogenic biallelic variants
notes: >-
Established disease genes extend beyond BBS1 and BBS10 and include core
BBSome subunits and related ciliary trafficking genes such as BBS2,
ARL6/BBS3, MKKS/BBS6, BBS9, and others.
evidence:
- reference: PMID:30614526
reference_title: "Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Molecular diagnosis during pregnancies remains a timely challenge for this
heterogeneous disease (22 known genes).
explanation: >-
This large molecularly confirmed series supports broad genetic
heterogeneity within classic BBS.
- reference: PMID:41219488
reference_title: "Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Biallelic pathogenic variants were identified in all patients, including
three novel variants in the ARL6/BBS3, BBS9, and BBS10 genes, observed in
four patients, including two siblings.
explanation: >-
This recent cohort shows that clinically confirmed BBS continues to arise
from multiple non-BBS1 genotypes.
pathophysiology:
- name: Pathogenic BBS gene defects
description: >-
Biallelic pathogenic variants in established BBS genes initiate classic
Bardet-Biedl syndrome.
genes:
- preferred_term: BBS1
term:
id: hgnc:966
label: BBS1
- preferred_term: BBS10
term:
id: hgnc:26291
label: BBS10
- preferred_term: BBS2
term:
id: hgnc:967
label: BBS2
- preferred_term: ARL6
term:
id: hgnc:13210
label: ARL6
- preferred_term: MKKS
term:
id: hgnc:7108
label: MKKS
evidence:
- reference: PMID:30614526
reference_title: "Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Molecular diagnosis during pregnancies remains a timely challenge for this
heterogeneous disease (22 known genes).
explanation: >-
This large prenatal molecular series supports disease initiation by
biallelic pathogenic variants across many established BBS genes.
- reference: PMID:41219488
reference_title: "Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Biallelic pathogenic variants were identified in all patients, including
three novel variants in the ARL6/BBS3, BBS9, and BBS10 genes, observed in
four patients, including two siblings.
explanation: >-
This recent cohort confirms that clinically diagnosed BBS is anchored by
biallelic pathogenic variants in established BBS genes.
downstream:
- target: Defective BBSome assembly
description: Disease-causing variants destabilize the BBSome or its assembly machinery.
- name: Defective BBSome assembly
description: >-
Pathogenic variants in core BBSome subunits and chaperonin-like BBS proteins
impair ordered assembly of the BBSome, the ciliary trafficking complex
central to BBS biology.
cellular_components:
- preferred_term: BBSome
term:
id: GO:0034464
label: BBSome
- preferred_term: primary cilium
term:
id: GO:0005929
label: cilium
evidence:
- reference: PMID:22500027
reference_title: "Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Three additional BBS genes (BBS6, BBS10, and BBS12) have homology to type
II chaperonins and interact with CCT/TRiC proteins and BBS7 to form a
complex termed the BBS-chaperonin complex. This complex is required for
BBSome assembly.
explanation: >-
This mechanistic study directly supports chaperonin-dependent failure of
BBSome assembly as an early causal step in BBS.
- reference: PMID:20080638
reference_title: "BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Our data demonstrate that BBS6, BBS10, and BBS12 are necessary for BBSome
assembly, and that impaired BBSome assembly contributes to the etiology of
BBS phenotypes associated with the loss of function of these three BBS
genes.
explanation: >-
This complementary paper independently supports BBSome assembly failure as
a proximal disease mechanism.
downstream:
- target: Ciliary membrane protein trafficking defect
description: An incompletely assembled BBSome fails to move selected cargos correctly through the ciliary compartment.
- name: Ciliary membrane protein trafficking defect
description: >-
Failure of an intact BBSome disrupts trafficking of signaling proteins and
other cargos into and within the ciliary compartment.
cellular_components:
- preferred_term: primary cilium
term:
id: GO:0005929
label: cilium
biological_processes:
- preferred_term: protein localization to cilium
term:
id: GO:0061512
label: protein localization to cilium
- preferred_term: intraciliary transport
term:
id: GO:0042073
label: intraciliary transport
evidence:
- reference: PMID:36699005
reference_title: "Ciliary signaling proteins are mislocalized in the brains of Bardet-Biedl syndrome 1-null mice."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
GPCR ciliary localization is disrupted in neurons from mouse models of the
ciliopathy Bardet-Biedl syndrome, with GPCRs failing to localize to cilia,
indicating the Bardet-Biedl syndrome proteins are required for trafficking
of G protein-coupled receptors into neuronal cilia.
explanation: >-
This mouse study directly supports defective ciliary cargo trafficking as a
general mechanistic consequence of BBS protein loss.
downstream:
- target: Hypothalamic leptin receptor signaling defect
description: Impaired neuronal ciliary trafficking perturbs hypothalamic satiety signaling.
- target: Photoreceptor outer-segment transport defect
description: High-throughput photoreceptor cargo delivery fails when ciliary trafficking is disrupted.
- target: Renal tubulointerstitial injury
description: Kidney epithelial cilia-dependent homeostasis is disrupted downstream of trafficking failure.
- target: Altered Sonic hedgehog-dependent limb patterning
description: Developmental ciliary signaling defects perturb limb-bud patterning.
- name: Hypothalamic leptin receptor signaling defect
description: >-
BBS proteins are required for leptin-receptor trafficking and
leptin-induced hypothalamic signaling, creating ciliary leptin resistance
and impaired satiety signaling.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
locations:
- preferred_term: hypothalamus
term:
id: UBERON:0001898
label: hypothalamus
biological_processes:
- preferred_term: JAK-STAT signaling
term:
id: GO:0007259
label: cell surface receptor signaling pathway via JAK-STAT
evidence:
- reference: PMID:19150989
reference_title: "Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Our data indicate that BBS proteins mediate LepR trafficking and that
impaired LepR signaling underlies energy imbalance in BBS.
explanation: >-
This mouse study directly connects BBS-protein loss to defective
hypothalamic leptin receptor trafficking and signaling.
- reference: PMID:21209035
reference_title: "Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients with BBS had higher leptin than expected for their degree of
adiposity, consistent with the notion that ciliopathy-induced leptin
signaling dysfunction is associated with leptin resistance.
explanation: >-
Human metabolic data support leptin resistance as a clinically observable
consequence of BBS-related satiety-pathway dysfunction.
downstream:
- target: Hyperphagia
description: Impaired satiety signaling increases hunger and food-seeking behavior.
- target: Obesity
description: Chronic positive energy balance drives early-onset obesity.
- name: Photoreceptor outer-segment transport defect
description: >-
In photoreceptors, defective ciliary transport mislocalizes rhodopsin and
other outer-segment cargo, leading to photoreceptor degeneration.
cell_types:
- preferred_term: photoreceptor cell
term:
id: CL:0000210
label: photoreceptor cell
locations:
- preferred_term: retina
term:
id: UBERON:0000966
label: retina
cellular_components:
- preferred_term: photoreceptor outer segment
term:
id: GO:0001750
label: photoreceptor outer segment
evidence:
- reference: PMID:15539463
reference_title: "Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Photoreceptor cell death is preceded by mislocalization of rhodopsin,
indicating a defect in transport.
explanation: >-
This model-organism study directly ties BBS-related transport failure to
the retinal degeneration branch of the disease.
downstream:
- target: Rod-cone dystrophy
description: Photoreceptor degeneration produces the invariant retinal dystrophy phenotype.
- target: Progressive visual loss
description: Ongoing photoreceptor loss causes worsening visual acuity over time.
- name: Renal tubulointerstitial injury
description: >-
Kidney involvement in BBS includes renal dysmorphism, impaired kidney
function, and chronic tubulointerstitial disease consistent with a renal
ciliopathy.
cell_types:
- preferred_term: nephron tubule epithelial cell
term:
id: CL:1000494
label: nephron tubule epithelial cell
locations:
- preferred_term: kidney
term:
id: UBERON:0002113
label: kidney
evidence:
- reference: PMID:20876674
reference_title: "Bardet-Biedl syndrome: a study of the renal and cardiovascular phenotypes in a French cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Renal abnormalities, including impairment of renal function and signs of
chronic interstitial nephropathy of dysplastic nature, were documented in
82% of the patients.
explanation: >-
This human cohort provides direct tissue-level support for renal
tubulointerstitial disease within BBS.
downstream:
- target: Renal abnormalities
description: Structural and functional kidney disease is a major clinical consequence.
- name: Altered Sonic hedgehog-dependent limb patterning
description: >-
BBS loss perturbs cilia-dependent Sonic hedgehog signaling during limb-bud
development, predisposing to postaxial digit duplication.
biological_processes:
- preferred_term: smoothened signaling pathway
term:
id: GO:0007224
label: smoothened signaling pathway
locations:
- preferred_term: limb bud
term:
id: UBERON:0004347
label: limb bud
evidence:
- reference: PMID:18381349
reference_title: "Genetic interaction between Bardet-Biedl syndrome genes and implications for limb patterning."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
We evaluated zebrafish fin bud patterning and observed altered Sonic
hedgehog (shh) expression and subsequent changes to fin skeletal elements.
explanation: >-
This in vivo developmental study supports altered hedgehog-dependent limb
patterning as the mechanistic basis for BBS polydactyly.
downstream:
- target: Postaxial polydactyly
description: Disrupted limb-bud patterning manifests clinically as postaxial extra digits.
phenotypes:
- name: Rod-cone dystrophy
category: Ocular
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Invariant retinal dystrophy with early rod dysfunction, progressive retinal
degeneration, and severe visual morbidity over time.
phenotype_term:
preferred_term: rod-cone dystrophy
term:
id: HP:0000510
label: Rod-cone dystrophy
evidence:
- reference: PMID:35886001
reference_title: "Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All patients had retinal dystrophy with morphologic changes of the retina.
explanation: >-
This specialist ophthalmic cohort supports retinal dystrophy as an
essentially invariant feature of molecularly confirmed BBS.
- reference: PMID:41219488
reference_title: "Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal dystrophy was the most common feature (94.1%), followed by
polydactyly (88.0%), obesity (68.0%), and renal anomalies (52.0%).
explanation: >-
This recent cohort provides direct frequency support for a very frequent
retinal dystrophy phenotype.
- name: Progressive visual loss
category: Ocular
description: >-
Visual acuity progressively declines from childhood, often reaching severe
impairment or blindness in later decades.
phenotype_term:
preferred_term: progressive visual loss
term:
id: HP:0000529
label: Progressive visual loss
evidence:
- reference: PMID:35886001
reference_title: "Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Visual acuity decreased from ~0.2 (decimal) at age 5 to blindness 0 at 50
years.
explanation: >-
This cohort provides direct longitudinal-style evidence for progressive
loss of vision across the lifespan in BBS.
- reference: PMID:22358239
reference_title: "Visual acuity and retinal function in patients with Bardet-Biedl syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In a relatively young cohort of patients with Bardet-Biedl syndrome, only
21% had 20/40 or better vision.
explanation: >-
This retinal-function study supports clinically important visual loss even
in a relatively young cohort.
- name: Obesity
category: Metabolic
frequency: FREQUENT
description: >-
Rapid early-childhood weight gain leads to persistent overweight or obesity
through childhood and adulthood.
phenotype_term:
preferred_term: obesity
term:
id: HP:0001513
label: Obesity
evidence:
- reference: PMID:32700463
reference_title: "Bardet-Biedl syndrome: Weight patterns and genetics in a rare obesity syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Despite normal birth weight, most individuals with BBS experience rapid
weight gain in early childhood, with high rates of overweight/obesity
sustained through adolescence.
explanation: >-
This large registry-based pediatric study supports obesity as a core and
early feature of BBS.
- reference: PMID:41219488
reference_title: "Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal dystrophy was the most common feature (94.1%), followed by
polydactyly (88.0%), obesity (68.0%), and renal anomalies (52.0%).
explanation: >-
This recent cohort provides direct frequency support for obesity as a
frequent BBS phenotype.
- name: Hyperphagia
category: Behavioral
description: >-
Pathologic hunger and food-seeking behavior contribute to the obesity burden
in BBS.
phenotype_term:
preferred_term: hyperphagia
term:
id: HP:0002591
label: Polyphagia
evidence:
- reference: PMID:23776152
reference_title: "Hyperphagia among patients with Bardet-Biedl syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Total hyperphagia questionnaire score was higher in BBS than controls
(27.6 ± 9.0 vs. 19.1 ± 7.9, P = 0.005).
explanation: >-
This controlled study shows that hyperphagic symptoms are increased in BBS
relative to BMI-matched controls.
- name: Postaxial polydactyly
category: Skeletal
frequency: FREQUENT
diagnostic: true
description: >-
Postaxial extra digits affecting hands or feet are a cardinal developmental
manifestation of BBS.
phenotype_term:
preferred_term: postaxial polydactyly
term:
id: HP:0100259
label: Postaxial polydactyly
evidence:
- reference: PMID:41219488
reference_title: "Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal dystrophy was the most common feature (94.1%), followed by
polydactyly (88.0%), obesity (68.0%), and renal anomalies (52.0%).
explanation: >-
This recent cohort provides direct frequency support for polydactyly as a
frequent primary BBS feature.
- reference: PMID:30614526
reference_title: "Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
postaxial polydactyly (82%) and renal cysts (78%) were the most prevalent
symptoms.
explanation: >-
This large molecularly confirmed prenatal cohort provides independent
support for frequent postaxial polydactyly.
- name: Renal abnormalities
category: Genitourinary
frequency: FREQUENT
description: >-
Structural and functional kidney disease includes renal dysmorphism, cystic
or dysplastic change, and impaired kidney function.
phenotype_term:
preferred_term: renal abnormalities
term:
id: HP:0000077
label: Abnormality of the kidney
evidence:
- reference: PMID:20876674
reference_title: "Bardet-Biedl syndrome: a study of the renal and cardiovascular phenotypes in a French cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Renal abnormalities, including impairment of renal function and signs of
chronic interstitial nephropathy of dysplastic nature, were documented in
82% of the patients.
explanation: >-
This national cohort supports renal involvement as a frequent and
clinically important component of BBS.
- reference: PMID:41219488
reference_title: "Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal dystrophy was the most common feature (94.1%), followed by
polydactyly (88.0%), obesity (68.0%), and renal anomalies (52.0%).
explanation: >-
This recent cohort confirms that renal involvement remains common but more
variable than retinal disease or polydactyly.
biochemical:
- name: Leptin
presence: Increased
biomarker_term:
preferred_term: leptin measurement
term:
id: NCIT:C74866
label: Leptin Measurement
notes: >-
Serum leptin is elevated beyond what would be expected for adiposity alone,
supporting clinical leptin resistance.
evidence:
- reference: PMID:21209035
reference_title: "Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients with BBS had higher leptin than expected for their degree of
adiposity, consistent with the notion that ciliopathy-induced leptin
signaling dysfunction is associated with leptin resistance.
explanation: >-
This metabolic study supports hyperleptinemia as a human biochemical
correlate of leptin resistance in BBS.
treatments:
- name: Setmelanotide
description: >-
MC4R agonist pharmacotherapy that bypasses upstream ciliopathy-related
satiety-pathway dysfunction and reduces bodyweight in Bardet-Biedl syndrome.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: setmelanotide
term:
id: NCIT:C152349
label: Setmelanotide
target_phenotypes:
- preferred_term: obesity
term:
id: HP:0001513
label: Obesity
evidence:
- reference: PMID:36356613
reference_title: "Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
32·3% (95% CI 16·7 to 51·4; p=0·0006) of patients aged 12 years or older
with Bardet-Biedl syndrome reached at least a 10% reduction in bodyweight
after 52 weeks of setmelanotide.
explanation: >-
This phase 3 trial provides direct evidence that MC4R agonism can reduce
bodyweight in BBS.
- reference: PMID:36356613
reference_title: "Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
These results support the use of setmelanotide and provided the necessary
evidence for approval of this drug as the first treatment for obesity in
patients with Bardet-Biedl syndrome.
explanation: >-
The trial interpretation explicitly supports setmelanotide as the approved
obesity-directed treatment for BBS.
- name: Kidney transplantation
description: >-
Organ transplantation is a viable treatment option for the subset of BBS
patients who progress to end-stage renal disease.
treatment_term:
preferred_term: organ transplantation
term:
id: MAXO:0010039
label: organ transplantation
evidence:
- reference: PMID:27245600
reference_title: "Renal transplantation in Bardet-Biedl Syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Although the frequency of obesity and other manifestations of the
metabolic syndrome warrant meticulous management in this high-risk
population, favorable long-term outcomes suggest that renal
transplantation is a viable option for patients with BBS and ESRD.
explanation: >-
This registry-based transplant study supports kidney transplantation for
the ESRD subset of BBS.