Bardet-Biedl Syndrome - Disorder Mechanisms

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Classifications

Harrison's Chapter

Mechanistic Nosology

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Inheritance

1

Autosomal recessive HP:0000007

Bardet-Biedl syndrome is classically autosomal recessive with clinically variable presentation. Complex inheritance is not typical for BBS1.

Autosomal recessive inheritance Expressivity: VARIABLE

Show evidence (3 references)

PMID:36374067 SUPPORT Human Clinical

"Bardet Biedl syndrome is an autosomal recessive ciliopathie."

States autosomal recessive inheritance.

PMID:19701229 SUPPORT Human Clinical

"Bardet-Biedl syndrome is a clinically variable condition associated with learning disabilities, progressive visual loss, obesity, polydactyly, hypogonadism, and cystic and fibrotic renal changes that can lead to renal failure."

Supports variable expressivity.

PMID:12524598 SUPPORT Human Clinical

"Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance."

Confirms autosomal recessive inheritance for BBS1 and notes complex inheritance is rare.

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Subtypes

3

BBS1

The most common subtype caused by mutations in the BBS1 gene.

Show evidence (2 references)

PMID:37612261 SUPPORT

"This study reports variants in BBS1 and BBS7 in patients with Bardet-Biedl syndrome from the Canadian Maritime provinces. The BBS1 variant NM_024649.5:c.1169T>G was identified as a recurrent variant in Prince Edward Island."

This supports the claim that mutations in the BBS1 gene are a common subtype of Bardet-Biedl syndrome.

PMID:32759308 PARTIAL

"More than half of BBS patients carry mutations in one of eight genes encoding for subunits of a protein complex, the BBSome, which mediates trafficking of ciliary cargoes. ... We show that the pre-BBSome is nucleated by BBS4 and assembled at pericentriolar satellites, followed by the..."

This explains the critical role of BBS1 in the assembly of the BBSome, further implicating it in Bardet-Biedl syndrome.

BBS2

Caused by mutations in the BBS2 gene, associated with similar features but can show some phenotypic variability.

Show evidence (2 references)

PMID:36672825 SUPPORT

"Patient 3 had Bardet-Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa,..."

The study shows that a mutation in the BBS2 gene can indeed cause Bardet-Biedl syndrome and the associated phenotypic variability in clinical findings.

PMID:34364070 NO_EVIDENCE

"Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment"

This study supports that mutations in the BBS2 gene can cause Bardet-Biedl syndrome, along with a spectrum of associated features, reinforcing the idea of phenotypic variability.

Other BBS Subtypes

Caused by mutations in various other BBS genes, including BBS3, BBS4, BBS5, and more.

Show evidence (4 references)

PMID:12876834 SUPPORT

"BBS is defined by the association of retinopathy, obesity, hypogonadism, renal dysfunction, postaxial polydactyly and mental retardation. This clinically complex syndrome is genetically heterogeneous with linkage to more than 6 loci, and 4 genes have been cloned so far."

This reference acknowledges the genetic heterogeneity of Bardet-Biedl Syndrome and mentions multiple BBS genes.

PMID:27170093 NO_EVIDENCE

"Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder and is classified as one of the ciliopathy."

Although this reference focuses on BBS3, it contributes to the recognition of different BBS subtypes caused by mutations in various BBS genes.

PMID:32165602 SUPPORT

"Bardet-Biedl syndrome (BBS) is a rare heterogenous autosomal recessive disease due to defects in primary cilia which until now, up to 21 types have been detected."

The reference highlights the heterogeneity of BBS and mentions the existence of multiple types of the syndrome, caused by different genetic mutations.

+ 1 more reference

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Pathophysiology

4

Ciliary Dysfunction

Defects in the function of primary cilia due to mutations in BBS genes lead to a wide range of symptoms.

Primary Cilium link

Show evidence (3 references)

PMID:26231314 SUPPORT

"From the analysis of the mutational burden in patients to the functional characterization of the BBS proteins, this syndrome has become a model for both understanding oligogenic patterns of inheritance and the biology of a particular cellular organelle: the primary cilium."

This excerpt supports the assertion that BBS mechanisms are related to defects in primary cilia function caused by mutations in BBS genes, leading to a wide range of symptoms.

PMID:29534263 PARTIAL

"The photoreceptor connecting cilium plays a leading role in these ciliopathy-related retinal dystrophies. Dysfunctional photoreceptor cilia cause the most severe type of retinal dystrophy: Leber's congenital amaurosis (LCA). The most common syndromic ciliopathies with an ocular manifestation are..."

This reference emphasizes the role of primary cilia dysfunction in BBS and its association with retinal dystrophies, supporting the statement.

PMID:33560420 SUPPORT

"One ciliopathy, Bardet-Biedl syndrome (BBS; OMIM 209900), presents with diverse clinical features, many of which are attributed to defects in ciliary signaling during both embryonic development and postnatal life"

This supports the statement by explaining that BBS symptoms are attributed to ciliary defects.

BBSome Assembly and Intraflagellar Transport Defects

The BBSome is an octameric protein complex (BBS1/2/4/5/7/8/9/BBIP1) whose assembly requires chaperonin-like proteins (BBS6, BBS10, BBS12). The BBSome cooperates with intraflagellar transport (IFT) machinery to regulate ciliary entry, retention, and retrieval of membrane proteins including GPCRs. Disruption of BBSome-mediated trafficking causes mislocalization of ciliary cargos and impaired ciliary signaling across multiple tissues.

Intraflagellar Transport link Protein Localization to Cilium link

BBSome link Ciliary Transition Zone link

Photoreceptor Connecting Cilium link

Hypothalamic Leptin Resistance

Impaired ciliary localization and trafficking of leptin receptors and other GPCRs (e.g., serotonin 5-HT2C receptor, MC4R) in hypothalamic POMC neurons due to BBSome dysfunction. This disrupts melanocortin signaling pathways that regulate appetite and energy homeostasis, leading to hyperphagia and obesity.

Neuron link

Regulation of Appetite link Leptin Receptor Signaling link

Hypothalamus link

Renal Ciliary Dysfunction

Renal tubular epithelial cells depend on primary cilia for proper solute handling and signaling. BBSome-mediated ciliary dysfunction disrupts these processes, leading to concentrating and diluting defects, progressive renal cysts, dysplasia, and chronic kidney disease.

Renal Tubular Epithelial Cell link

Kidney link

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Causal Graph

graph LR
    Renal_Anomalies["Renal Anomalies"]
    Renal_Ciliary_Dysfunction["Renal Ciliary Dysfunction"]
    Hyperphagia["Hyperphagia"]
    Night_Blindness["Night Blindness"]
    Hirschsprung_Disease["Hirschsprung Disease"]
    BBSome_Assembly_and_Intraflagellar_Transport_Defects["BBSome Assembly and Intraflagellar Transport Defects"]
    Truncal_Obesity["Truncal Obesity"]
    Ciliary_Dysfunction["Ciliary Dysfunction"]
    Progressive_Vision_Loss["Progressive Vision Loss"]
    Congenital_Heart_Defects["Congenital Heart Defects"]
    Developmental_Delay["Developmental Delay"]
    Hypothalamic_Leptin_Resistance["Hypothalamic Leptin Resistance"]
    Hypogonadism["Hypogonadism"]
    Behavioral_Abnormalities["Behavioral Abnormalities"]
    Retinitis_Pigmentosa["Retinitis Pigmentosa"]
    Polydactyly["Polydactyly"]
    Dysmorphic_Facial_Features["Dysmorphic Facial Features"]
    Intellectual_Disability["Intellectual Disability"]

    Ciliary_Dysfunction --> BBSome_Assembly_and_Intraflagellar_Transport_Defects
    Ciliary_Dysfunction --> Hypothalamic_Leptin_Resistance
    Ciliary_Dysfunction --> Renal_Ciliary_Dysfunction
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Retinitis_Pigmentosa
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Night_Blindness
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Progressive_Vision_Loss
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Polydactyly
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Developmental_Delay
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Intellectual_Disability
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Behavioral_Abnormalities
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Dysmorphic_Facial_Features
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Congenital_Heart_Defects
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Hypogonadism
    BBSome_Assembly_and_Intraflagellar_Transport_Defects --> Hirschsprung_Disease
    Hypothalamic_Leptin_Resistance --> Hyperphagia
    Hypothalamic_Leptin_Resistance --> Truncal_Obesity
    Renal_Ciliary_Dysfunction --> Renal_Anomalies
    Retinitis_Pigmentosa --> Night_Blindness
    Retinitis_Pigmentosa --> Progressive_Vision_Loss

    style Renal_Anomalies fill:#fef3c7
    style Renal_Ciliary_Dysfunction fill:#dbeafe
    style Hyperphagia fill:#fef3c7
    style Night_Blindness fill:#fef3c7
    style Hirschsprung_Disease fill:#fef3c7
    style BBSome_Assembly_and_Intraflagellar_Transport_Defects fill:#dbeafe
    style Truncal_Obesity fill:#fef3c7
    style Ciliary_Dysfunction fill:#dbeafe
    style Progressive_Vision_Loss fill:#fef3c7
    style Congenital_Heart_Defects fill:#fef3c7
    style Developmental_Delay fill:#fef3c7
    style Hypothalamic_Leptin_Resistance fill:#dbeafe
    style Hypogonadism fill:#fef3c7
    style Behavioral_Abnormalities fill:#fef3c7
    style Retinitis_Pigmentosa fill:#fef3c7
    style Polydactyly fill:#fef3c7
    style Dysmorphic_Facial_Features fill:#fef3c7
    style Intellectual_Disability fill:#fef3c7

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Phenotypes

15

Endocrine(1) Eye(3) Limbs(1) Nervous System(3) Growth(1) Other(6)

Endocrine 1

Hypogonadism OCCASIONAL Hypogonadism (HP:0000135)

In both males and females

Show evidence (4 references)

PMID:7726222 PARTIAL

"The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism (described mainly in males)."

The literature mentions hypogenitalism mainly in males but does not provide evidence for its frequency or occurrence in females.

PMID:19327768 PARTIAL

"To report a patient with Bardet-Biedl syndrome (BBS) with known hypogonadotrophic hypogonadism who developed spontaneous reversal of hypogonadism in adulthood."

This study reports hypogonadism in a male patient but does not discuss its frequency or occurrence in females.

PMID:31696011 PARTIAL

"The major features of this syndrome are cone-rod dystrophy, polydactyly, obesity, learning disabilities, hypogonadism in males, renal anomalies, nystagmus, speech disorders, developmental delay, polyuria/polydipsia, ataxia, and poor coordination/clumsiness."

The literature mentions hypogonadism in males but does not provide information about its occurrence in females or its frequency.

+ 1 more reference

Eye 3

Retinitis Pigmentosa VERY_FREQUENT Rod-cone dystrophy (HP:0000510)

Sequelae: Night Blindness Progressive Vision Loss

Show evidence (4 references)

PMID:15690372 SUPPORT

"Bardet-Biedl syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder."

The literature confirms that RP is a high-frequency ophthalmologic phenotype in Bardet-Biedl syndrome.

PMID:36481880 PARTIAL

"Retinitis pigmentosa (RP) is a set of symptoms including tunnel vision, night blindness, and progressive vision loss...as part of a larger syndrome (syndromic)..."

The study acknowledges that RP includes night blindness and progressive vision loss, supporting the sequelae mentioned in the statement.

PMID:35791150 SUPPORT

"Patients with RP in LMBB syndrome present mainly in the first to second decade of life with severe visual acuity impairment to blindness early in life."

RP is reported as a predominant feature in patients with Bardet-Biedl syndrome, confirming the high frequency of this phenotype.

+ 1 more reference

Night Blindness FREQUENT Nyctalopia (HP:0000662)

Progressive Vision Loss FREQUENT Progressive visual loss (HP:0000529)

Limbs 1

Polydactyly FREQUENT Polydactyly (HP:0010442)

Show evidence (2 references)

PMID:20876674 PARTIAL

"Renal abnormalities, including impairment of renal function and signs of chronic interstitial nephropathy of dysplastic nature, were documented in 82% of the patients."

The statement is partially supported because renal abnormalities are common in Bardet-Biedl Syndrome, but the frequency and diagnosis related to polydactyly is not addressed.

PMID:6487184 PARTIAL

"The Bardet-Biedl syndrome is characterized by five main features: obesity, polydactyly, pigmentary retinopathy, mental deficiency and hypogonadism; recently a sixth feature, renal disease, has been described."

The reference confirms that both polydactyly and renal disease are features of Bardet-Biedl Syndrome, but it does not specify the diagnostic frequency relationship of polydactyly within renal phenotypes.

Nervous System 3

Hyperphagia VERY_FREQUENT Polyphagia (HP:0002591)

Intellectual Disability FREQUENT Intellectual disability (HP:0001249)

Show evidence (2 references)

PMID:36374067 PARTIAL

"Bardet Biedl syndrome... is a pleiotropic disorder characterised by retinal dystrophy, renal dysfunction, polydactyly, obesity, cognitive deficit and hypogenitalism."

The reference mentions cognitive deficits as a characteristic of Bardet-Biedl Syndrome, which can include intellectual disability. However, it does not explicitly state the frequency of intellectual disability, thus it partially supports the statement.

PMID:19778711 PARTIAL

"Joubert syndrome (JS) is a primarily autosomal recessive condition characterized by... intellectual disability... Variable features include... polydactyly... disorders called ciliopathies."

This reference is about Joubert syndrome, which is another ciliopathy like Bardet-Biedl Syndrome. It mentions intellectual disability related to ciliopathies in general but does not directly correlate it with Bardet-Biedl Syndrome's frequency.

Developmental Delay OCCASIONAL Global developmental delay (HP:0001263)

Show evidence (2 references)

PMID:33040131 PARTIAL

"Clinical presentation of this rare condition may affect locomotive, neurological, cardio-vascular, endocrine and metabolic systems."

The abstract mentions that Bardet-Biedl syndrome can affect the neurological system, which can include developmental delay.

PMID:24194441 SUPPORT

"On the age appropriate Wechsler scale, the mean Verbal Comprehension was 81 (n = 36), Working Memory was 81 (n = 36), Perceptual Reasoning was 78 (n = 24) and Full Scale IQ was 75 (n = 26)."

The abstract provides evidence of reduced cognitive functions in patients with Bardet-Biedl syndrome, indicating developmental delays.

Growth 1

Truncal Obesity VERY_FREQUENT Truncal obesity (HP:0001956)

Show evidence (4 references)

PMID:32700463 PARTIAL

"Despite normal birth weight, most individuals with BBS experience rapid weight gain in early childhood, with high rates of overweight/obesity sustained through adolescence."

The literature mentions high rates of obesity in individuals with Bardet-Biedl Syndrome but does not specifically categorize it as truncal obesity.

PMID:6487184 PARTIAL

"All had subnormal intelligence, twelve were obese, ten had polydactyly, eight hypogonadism, and two had renal disease."

While obesity is mentioned as a prevalent phenotype, there is no specific mention of truncal obesity.

PMID:29127258 PARTIAL

"CONCLUSION: CEP19 encodes a centrosomal and ciliary protein, as all BBS genes do. Another truncating mutation p.Arg82* has been reported as responsible for morbid obesity in a family; however, in the family we present, not all homozygotes are obese, although some are severely obese."

The reference mentions severe obesity related to BBS genes but not truncal obesity specifically.

+ 1 more reference

Other 6

Renal Anomalies FREQUENT

Show evidence (3 references)

PMID:11096143 SUPPORT

"The spectrum of disease includes diverse malformations of the kidney and lower urinary tract."

Renal anomalies are mentioned as part of the disease spectrum in Bardet-Biedl syndrome.

PMID:28662344 SUPPORT

"Since the comorbid spectrum of BBS phenotypes spans... renal disease, obesity, sleep apnea, cardiovascular disease, and cognitive disorders..."

Renal disease is listed as one of the common phenotypes associated with Bardet-Biedl Syndrome.

PMID:32165602 PARTIAL

"This type can cause severe and delayed onset renal failure."

Bardet-Biedl type 9 is noted to cause severe and delayed onset renal failure, supporting the common occurrence of renal anomalies.

Renal Anomalies FREQUENT

Includes: - Renal cysts - Renal hypoplasia/dysplasia - Hydronephrosis

Show evidence (4 references)

PMID:26076793 SUPPORT

"Renal abnormalities have been recognized as a cardinal feature of the disease with serious prognostic implication."

The study highlights renal abnormalities as a significant aspect of Bardet-Biedl syndrome, supporting the statement about the frequent occurrence of renal anomalies.

PMID:31419725 PARTIAL

"Renal ciliopathies are a group of disorders characterised by nephronophthisis, cystic kidneys or renal cystic dysplasia."

The article mentions renal cystic dysplasia as part of renal ciliopathies, which includes Bardet-Biedl syndrome, supporting the statement.

PMID:7726222 SUPPORT

"The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism."

The article explicitly mentions renal abnormalities as a major manifestation of Bardet-Biedl syndrome, supporting the statement.

+ 1 more reference

Behavioral Abnormalities FREQUENT

Includes impulsivity, emotional lability, disinhibition

Show evidence (6 references)

PMID:24194441 PARTIAL

"A wide range of behavioral issues were endorsed on questionnaires given to parents. Most had social skill deficits but no pattern of either externalizing or internalizing problems."

The study mentions a wide range of behavioral issues and social skill deficits but does not specifically mention impulsivity, emotional lability, or disinhibition.

PMID:23776152 NO_EVIDENCE

"CONCLUSION: Appetite dysregulation may contribute to obesity in BBS."

This study focuses on hyperphagia and appetite dysregulation, not on behavioral abnormalities such as impulsivity, emotional lability, or disinhibition.

PMID:7726222 NO_EVIDENCE

"The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism."

This study does not address behavioral abnormalities in Bardet-Biedl Syndrome.

+ 3 more references

Dysmorphic Facial Features FREQUENT

Includes deep-set eyes, flat nasal bridge, large ears

Show evidence (2 references)

PMID:27170093 PARTIAL

"The patients manifest a characteristic craniofacial dysmorphology but the effects of Bbs3 deficiency in the developmental process during the craniofacial pathogenesis are still incompletely understood."

The literature confirms craniofacial dysmorphology in Bardet-Biedl Syndrome, but does not provide specific details on the frequency or exact features such as deep-set eyes, flat nasal bridge, and large ears.

PMID:28662344 PARTIAL

"Dental anomalies are present in a majority of individuals affected by BBS due to abnormal embryonic orofacial and tooth development."

The literature mentions dental anomalies and orofacial development issues in Bardet-Biedl Syndrome, but does not specifically discuss the frequency or detailed craniofacial features listed in the statement.

Congenital Heart Defects OCCASIONAL

Show evidence (2 references)

PMID:7802002 PARTIAL

"Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome."

The study reports cardiac involvement in 50% of cases, but it does not specify that congenital heart defects are only 'occasional'.

PMID:33433911 NO_EVIDENCE

"Atrioventricular canal defect is the classic congenital heart disease in Bardet-Biedl syndrome."

This reference indicates that atrioventricular canal defect is a classic congenital heart disease in Bardet-Biedl syndrome, but it does not provide information on the frequency being 'occasional'.

Hirschsprung Disease OCCASIONAL

Show evidence (1 reference)

PMID:23001136 PARTIAL

"A number of other autosomal recessive syndromes include the Shah-Waardenburg, the Bardet-Biedl and Cartilage-hair hypoplasia, Goldberg-Shprintzen syndromes and other syndromes related to cholesterol and fat metabolism among others."

The reference mentions Bardet-Biedl Syndrome (BBS) in the context of syndromes associated with Hirschsprung's disease (HSCR), but it does not specify the frequency of this association. Hence, it partially supports the statement without confirming the frequency as 'occasional'.

🧬

Genetic Associations

3

BBS1 (Pathogenic Variants)

Show evidence (5 references)

PMID:27625843 PARTIAL

"There are 17 BBS genes (BBS1-BBS17) described to date, which explain 70-80% of the patients clinically diagnosed, therefore more BBS genes remain to be identified."

The literature confirms that BBS1 is one of the genes associated with Bardet-Biedl syndrome, but it does not specify that BBS1 is the most common subtype.

PMID:22940089 SUPPORT

"PURPOSE: To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation... Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation."

The literature supports the pathogenicity of the BBS1 mutation, suggesting it as a common and consistent cause of the disease.

PMID:36833331 PARTIAL

"Whole-exome sequencing revealed 9 pathogenic variants in six genes associated with BBS in 12 families... Three known variants were detected in the BBS1, BBS2, and BBS7 genes."

The study mentions BBS1 among others but does not establish it as the most common subtype.

+ 2 more references

BBS2 (Pathogenic Variants)

Show evidence (2 references)

PMID:38407766 PARTIAL

"Our results identified the founder variant c.471G > A in the BBS2 gene in the Baloch ethnicity of the Iranian population. This finding can guide the diagnostic approach of this syndrome in future studies."

This indicates a common pathogenic variant in the BBS2 gene within a specific population, supporting the statement that BBS2 is associated with pathogenic variants.

PMID:12677556 PARTIAL

"Bardet-Biedl syndrome is a genetically and clinically heterogeneous disorder caused by mutations in at least seven loci (BBS1-7), five of which are cloned (BBS1, BBS2, BBS4, BBS6, and BBS7)."

This provides evidence that BBS2 is one of the BBS genes associated with pathogenic variants, supporting the claim in the statement.

Other BBS Genes (Pathogenic Variants)

Show evidence (5 references)

PMID:37239474 SUPPORT

"Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes."

The literature supports the genetic association of BBS with pathogenic variants in multiple genes beyond BBS1. The abstract mentions 22 known genes related to BBS.

PMID:27984625 SUPPORT

"So far 21 candidate genes have been discovered, and mutations of such genes can all cause the BBS phenotype."

This reference also indicates that multiple BBS genes, beyond just one, are associated with the disease.

PMID:37612261 SUPPORT

"This study reports variants in BBS1 and BBS7 in patients with Bardet-Biedl syndrome from the Canadian Maritime provinces."

The reference mentions that variants in BBS1 and BBS7 are observed, supporting the genetic heterogeneity of BBS.

+ 2 more references

💊

Treatments

6

Supportive Therapy MAXO:0000011

Addressing specific symptoms like vision support, weight management, and physical therapy.

Show evidence (5 references)

PMID:15852167 NO_EVIDENCE

"Based on the history, presentation, ophthalmic clinical examination, obesity, mental retardation and dental alterations, the patient was diagnosed with Bardet-Biedl syndrome."

The case report discusses the management of symptoms like vision loss and obesity, which aligns with supportive therapy addressing specific symptoms.

PMID:29754569 PARTIAL

"Advances in the understanding of ciliary biology and diagnostic techniques have opened up the prospect of treating BBS in a patient-specific manner."

The article mentions ongoing research in personalized medicine for BBS, focusing on treatments addressing specific symptoms, which supports the idea of supportive therapy.

PMID:36647077 PARTIAL

"This study highlights the need to address the impaired health-related quality of life in Bardet-Biedl syndrome, and supports utility of setmelanotide for reducing this burden."

The study discusses treatments impacting quality of life related to obesity, which is part of supportive therapy.

+ 2 more references

Genetic Counseling MAXO:0000079

For affected individuals and families to understand inheritance patterns, risks, and implications.

Show evidence (1 reference)

PMID:20301537 SUPPORT

"Provide an evaluation strategy to identify the genetic cause of Bardet-Biedl syndrome in a proband (when possible); 4."

The overview highlights the importance of genetic counseling for identifying the genetic cause of the syndrome, supporting its role as a treatment component.

Surgical Interventions MAXO:0000004

For polydactyly or other structural anomalies as needed.

Dietary and Lifestyle Modifications MAXO:0000088

To manage obesity and associated metabolic conditions.

Show evidence (4 references)

PMID:38302651 PARTIAL

"We review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery."

Bardet-Biedl Syndrome (BBS) metabolic management mentions both dietary and lifestyle approaches, which include weight loss strategies.

PMID:27356116 PARTIAL

"Comprehensive lifestyle interventions, including nutrition, physical activity, and behavioral therapy, are the foundation for clinical obesity management."

Although not specific to BBS, this reference supports the use of lifestyle modifications for managing obesity.

PMID:36647077 PARTIAL

"Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity...patients reported clinically meaningful improvements across multiple health-related quality of life measures."

This study involving BBS patients includes dietary and lifestyle modifications as part of the treatment to manage obesity.

+ 1 more reference

Gene Therapy MAXO:0001001

Experimental gene augmentation therapy to preserve retinal function in BBS-related retinal degeneration.

Show evidence (1 reference)

PMID:36700052 SUPPORT

"We show that subretinal gene therapy slowed photoreceptor cell death and preserved retinal function in treated eyes. Notably, cone photoreceptors regained their electrical function after gene augmentation."

The article reports on gene therapy to manage vision loss in BBS, showing promising results in preserving retinal function.

Setmelanotide MAXO:0000058

Drug: setmelanotide ↗

An MC4R (melanocortin-4 receptor) agonist that activates the melanocortin pathway downstream of impaired leptin receptor signaling. Reduces hyperphagia and promotes weight loss in patients with BBS-associated obesity by bypassing the defective ciliary GPCR trafficking.

🌍

Environmental Factors

1

Not Applicable

There are no significant environmental factors specifically associated with the onset of Bardet-Biedl syndrome.

Show evidence (3 references)

PMID:29161709 NO_EVIDENCE

"Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders."

The article emphasizes that BBS is inherited and does not highlight any specific environmental factors associated with the onset of the syndrome.

PMID:36374067 NO_EVIDENCE

"Bardet Biedl syndrome is an autosomal recessive ciliopathie... Diagnosis is based on clinical features. Molecular genetic testing is available."

This reference explains that BBS is an autosomal recessive ciliopathy, focusing on genetic causes rather than environmental factors.

PMID:29409041 NO_EVIDENCE

"We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects."

While the article describes metabolic characteristics, it does not associate the onset of BBS with environmental factors.

🔬

Biochemical Markers

1

Elevated Serum Leptin

Show evidence (2 references)

PMID:21514177 PARTIAL

"Bardet-Biedl Syndrome (BBS) is a rare human hereditary disorder associated with several features including obesity... recent evidence pointing to aberrations in hypothalamic action of leptin. Indeed, BBS proteins have emerged as important mediators of leptin receptor trafficking, and loss of BBS..."

The article discusses how loss of BBS genes results in leptin resistance due to abnormal leptin receptor handling, pointing towards elevated serum leptin.

PMID:37919024 NO_EVIDENCE

"Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin..."

The reference mentions that Bardet-Biedl Syndrome is a ciliopathy with mechanisms converging on the leptin pathway, suggesting a role for leptin in the syndrome.

{ }

Source YAML

click to show

name: Bardet-Biedl Syndrome
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-02-27T21:52:54Z'
description: Bardet-Biedl syndrome is a rare autosomal recessive ciliopathy characterized by rod-cone dystrophy leading to blindness, obesity, polydactyly, renal anomalies, learning difficulties, and hypogonadism. It results from mutations in genes encoding components of the BBSome, a protein complex essential for ciliary trafficking.
category: Genetic
parents:
- Syndromic Obesity
- Ciliopathy
has_subtypes:
- name: BBS1
  description: The most common subtype caused by mutations in the BBS1 gene.
  evidence:
  - reference: PMID:37612261
    supports: SUPPORT
    snippet: This study reports variants in BBS1 and BBS7 in patients with Bardet-Biedl syndrome from the Canadian Maritime provinces. The BBS1 variant NM_024649.5:c.1169T>G was identified as a recurrent variant in Prince Edward Island.
    explanation: This supports the claim that mutations in the BBS1 gene are a common subtype of Bardet-Biedl syndrome.
  - reference: PMID:32759308
    supports: PARTIAL
    snippet: More than half of BBS patients carry mutations in one of eight genes encoding for subunits of a protein complex, the BBSome, which mediates trafficking of ciliary cargoes. ... We show that the pre-BBSome is nucleated by BBS4 and assembled at pericentriolar satellites, followed by the translocation of the BBSome into the ciliary base mediated by BBS1.
    explanation: This explains the critical role of BBS1 in the assembly of the BBSome, further implicating it in Bardet-Biedl syndrome.
- name: BBS2
  description: Caused by mutations in the BBS2 gene, associated with similar features but can show some phenotypic variability.
  evidence:
  - reference: PMID:36672825
    supports: SUPPORT
    snippet: Patient 3 had Bardet-Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation.
    explanation: The study shows that a mutation in the BBS2 gene can indeed cause Bardet-Biedl syndrome and the associated phenotypic variability in clinical findings.
  - reference: PMID:34364070
    supports: NO_EVIDENCE
    snippet: Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment
    explanation: This study supports that mutations in the BBS2 gene can cause Bardet-Biedl syndrome, along with a spectrum of associated features, reinforcing the idea of phenotypic variability.
- name: Other BBS Subtypes
  description: Caused by mutations in various other BBS genes, including BBS3, BBS4, BBS5, and more.
  evidence:
  - reference: PMID:12876834
    supports: SUPPORT
    snippet: BBS is defined by the association of retinopathy, obesity, hypogonadism, renal dysfunction, postaxial polydactyly and mental retardation. This clinically complex syndrome is genetically heterogeneous with linkage to more than 6 loci, and 4 genes have been cloned so far.
    explanation: This reference acknowledges the genetic heterogeneity of Bardet-Biedl Syndrome and mentions multiple BBS genes.
  - reference: PMID:27170093
    supports: NO_EVIDENCE
    snippet: Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder and is classified as one of the ciliopathy.
    explanation: Although this reference focuses on BBS3, it contributes to the recognition of different BBS subtypes caused by mutations in various BBS genes.
  - reference: PMID:32165602
    supports: SUPPORT
    snippet: Bardet-Biedl syndrome (BBS) is a rare heterogenous autosomal recessive disease due to defects in primary cilia which until now, up to 21 types have been detected.
    explanation: The reference highlights the heterogeneity of BBS and mentions the existence of multiple types of the syndrome, caused by different genetic mutations.
  - reference: PMID:36325687
    supports: SUPPORT
    snippet: 'Mutation screening demonstrated four novel mutations: c.613C>T; p.Q205* in the BBS5 gene, c.1391C>G; p.S464* in the BBS10 gene, and c.155delC; p.S52* and c.1584T>G; p.Y528* in the BBS12 gene.'
    explanation: This study identifies mutations in multiple BBS genes, supporting the statement that BBS comprises various subtypes caused by different genetic mutations.
prevalence:
- population: Global
  percentage: 0.00001-0.00003
  evidence:
  - reference: PMID:22109794
    supports: PARTIAL
    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: The prevalence range provided in the literature is specific to certain populations, but does suggest that globally, the prevalence could fall within the stated range percentage (0.00001-0.00003).
  - reference: PMID:37137806
    supports: NO_EVIDENCE
    snippet: 'AIMS: We described the updated global IBD epidemiology results based on the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD).'
    explanation: This paper deals with inflammatory bowel disease (IBD) and provides no direct evidence about the global prevalence of Bardet-Biedl Syndrome.
inheritance:
- name: Autosomal recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  expressivity: VARIABLE
  description: >
    Bardet-Biedl syndrome is classically autosomal recessive with clinically variable
    presentation. Complex inheritance is not typical for BBS1.
  evidence:
  - reference: PMID:36374067
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bardet Biedl syndrome is an autosomal recessive ciliopathie.
    explanation: States autosomal recessive inheritance.
  - reference: PMID:19701229
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Bardet-Biedl syndrome is a clinically variable condition associated with learning disabilities, progressive visual loss, obesity, polydactyly, hypogonadism, and cystic and fibrotic renal changes that can lead to renal failure.
    explanation: Supports variable expressivity.
  - reference: PMID:12524598
    supports: SUPPORT
    snippet: Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance.
    evidence_source: HUMAN_CLINICAL
    explanation: Confirms autosomal recessive inheritance for BBS1 and notes complex inheritance is rare.
pathophysiology:
- name: Ciliary Dysfunction
  description: Defects in the function of primary cilia due to mutations in BBS genes lead to a wide range of symptoms.
  cellular_components:
  - preferred_term: Primary Cilium
    term:
      id: GO:0005929
      label: cilium
  evidence:
  - reference: PMID:26231314
    supports: SUPPORT
    snippet: 'From the analysis of the mutational burden in patients to the functional characterization of the BBS proteins, this syndrome has become a model for both understanding oligogenic patterns of inheritance and the biology of a particular cellular organelle: the primary cilium.'
    explanation: This excerpt supports the assertion that BBS mechanisms are related to defects in primary cilia function caused by mutations in BBS genes, leading to a wide range of symptoms.
  - reference: PMID:29534263
    supports: PARTIAL
    snippet: 'The photoreceptor connecting cilium plays a leading role in these ciliopathy-related retinal dystrophies. Dysfunctional photoreceptor cilia cause the most severe type of retinal dystrophy: Leber''s congenital amaurosis (LCA). The most common syndromic ciliopathies with an ocular manifestation are Bardet-Biedl syndrome (BBS) and Usher syndrome.'
    explanation: This reference emphasizes the role of primary cilia dysfunction in BBS and its association with retinal dystrophies, supporting the statement.
  - reference: PMID:33560420
    supports: SUPPORT
    snippet: One ciliopathy, Bardet-Biedl syndrome (BBS; OMIM 209900), presents with diverse clinical features, many of which are attributed to defects in ciliary signaling during both embryonic development and postnatal life
    explanation: This supports the statement by explaining that BBS symptoms are attributed to ciliary defects.
  downstream:
  - target: BBSome Assembly and Intraflagellar Transport Defects
    description: Pathogenic BBS variants disrupt cargo trafficking across the primary cilium.
  - target: Hypothalamic Leptin Resistance
    description: Defective neuronal ciliary GPCR trafficking impairs satiety signaling.
  - target: Renal Ciliary Dysfunction
    description: Tubular mechano- and chemo-sensing fails when ciliary signaling is impaired.
- name: BBSome Assembly and Intraflagellar Transport Defects
  description: The BBSome is an octameric protein complex (BBS1/2/4/5/7/8/9/BBIP1) whose assembly requires chaperonin-like proteins (BBS6, BBS10, BBS12). The BBSome cooperates with intraflagellar transport (IFT) machinery to regulate ciliary entry, retention, and retrieval of membrane proteins including GPCRs. Disruption of BBSome-mediated trafficking causes mislocalization of ciliary cargos and impaired ciliary signaling across multiple tissues.
  cellular_components:
  - preferred_term: BBSome
    term:
      id: GO:0034464
      label: BBSome
  - preferred_term: Ciliary Transition Zone
    term:
      id: GO:0035869
      label: ciliary transition zone
  biological_processes:
  - preferred_term: Intraflagellar Transport
    term:
      id: GO:0042073
      label: intraflagellar transport
  - preferred_term: Protein Localization to Cilium
    term:
      id: GO:0061512
      label: protein localization to cilium
  locations:
  - preferred_term: Photoreceptor Connecting Cilium
    term:
      id: GO:0042622
      label: photoreceptor inner segment
  notes: In photoreceptors, the connecting cilium serves as a stringent gate where high-throughput trafficking of outer segment proteins occurs. Failure of BBSome/IFT trafficking causes protein mislocalization and photoreceptor degeneration.
  evidence: []
  downstream:
  - target: Retinitis Pigmentosa
    description: Mislocalized phototransduction proteins drive progressive retinal degeneration.
  - target: Night Blindness
    description: Early rod photoreceptor dysfunction manifests as nyctalopia.
  - target: Progressive Vision Loss
    description: Continued photoreceptor loss causes worsening visual acuity and field deficits.
  - target: Polydactyly
    description: Developmental Hedgehog/ciliary signaling disruption alters limb patterning.
  - target: Developmental Delay
    description: Multisystem ciliary signaling deficits impair neurodevelopmental progress.
  - target: Intellectual Disability
    description: Abnormal neuronal ciliary signaling contributes to cognitive impairment.
  - target: Behavioral Abnormalities
    description: Neurocircuit developmental effects contribute to behavioral dysregulation.
  - target: Dysmorphic Facial Features
    description: Craniofacial morphogenesis is perturbed by ciliary developmental signaling defects.
  - target: Congenital Heart Defects
    description: Altered left-right and outflow tract signaling increases congenital heart anomaly risk.
  - target: Hypogonadism
    description: Neuroendocrine and gonadal ciliary defects can impair pubertal and gonadal function.
  - target: Hirschsprung Disease
    description: Developmental signaling abnormalities can disrupt enteric nervous system maturation.
- name: Hypothalamic Leptin Resistance
  description: Impaired ciliary localization and trafficking of leptin receptors and other GPCRs (e.g., serotonin 5-HT2C receptor, MC4R) in hypothalamic POMC neurons due to BBSome dysfunction. This disrupts melanocortin signaling pathways that regulate appetite and energy homeostasis, leading to hyperphagia and obesity.
  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: Regulation of Appetite
    term:
      id: GO:0032098
      label: regulation of appetite
  - preferred_term: Leptin Receptor Signaling
    term:
      id: GO:0038110
      label: interleukin-35-mediated signaling pathway
  notes: BBSome proteins are essential for trafficking GPCRs within hypothalamic cilia, and their loss results in leptin resistance despite elevated serum leptin levels.
  evidence: []
  downstream:
  - target: Hyperphagia
    description: Reduced leptin and melanocortin signaling weakens satiety responses.
  - target: Truncal Obesity
    description: Chronic positive energy balance from impaired appetite control drives obesity.
- name: Renal Ciliary Dysfunction
  description: Renal tubular epithelial cells depend on primary cilia for proper solute handling and signaling. BBSome-mediated ciliary dysfunction disrupts these processes, leading to concentrating and diluting defects, progressive renal cysts, dysplasia, and chronic kidney disease.
  cell_types:
  - preferred_term: Renal Tubular Epithelial Cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  locations:
  - preferred_term: Kidney
    term:
      id: UBERON:0002113
      label: kidney
  notes: Renal abnormalities are a cardinal feature with serious prognostic implications, often progressing to end-stage renal disease.
  evidence: []
  downstream:
  - target: Renal Anomalies
    description: Defective tubular ciliary signaling drives cystic change, dysplasia, and chronic kidney disease.
phenotypes:
- category: Ophthalmologic
  name: Retinitis Pigmentosa
  description: Progressive rod-cone dystrophy leading to night blindness in childhood and progressive vision loss, often resulting in legal blindness by early adulthood.
  frequency: VERY_FREQUENT
  diagnostic: true
  sequelae:
  - target: Night Blindness
  - target: Progressive Vision Loss
  evidence:
  - reference: PMID:15690372
    supports: SUPPORT
    snippet: Bardet-Biedl syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder.
    explanation: The literature confirms that RP is a high-frequency ophthalmologic phenotype in Bardet-Biedl syndrome.
  - reference: PMID:36481880
    supports: PARTIAL
    snippet: Retinitis pigmentosa (RP) is a set of symptoms including tunnel vision, night blindness, and progressive vision loss...as part of a larger syndrome (syndromic)...
    explanation: The study acknowledges that RP includes night blindness and progressive vision loss, supporting the sequelae mentioned in the statement.
  - reference: PMID:35791150
    supports: SUPPORT
    snippet: Patients with RP in LMBB syndrome present mainly in the first to second decade of life with severe visual acuity impairment to blindness early in life.
    explanation: RP is reported as a predominant feature in patients with Bardet-Biedl syndrome, confirming the high frequency of this phenotype.
  - reference: PMID:31864384
    supports: PARTIAL
    snippet: Inherited retinal dystrophies are major cause of severe progressive vision loss in children.
    explanation: Retinal dystrophies, including RP, are significant causes of progressive vision loss, congruent with the statement's listed sequelae.
  phenotype_term:
    preferred_term: Retinitis Pigmentosa
    term:
      id: HP:0000510
      label: Rod-cone dystrophy
- category: Skeletal
  name: Polydactyly
  description: Postaxial polydactyly, typically presenting as extra digits on the ulnar side of the hands and/or fibular side of the feet.
  frequency: FREQUENT
  diagnostic: true
  evidence:
  - reference: PMID:20876674
    supports: PARTIAL
    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: The statement is partially supported because renal abnormalities are common in Bardet-Biedl Syndrome, but the frequency and diagnosis related to polydactyly is not addressed.
  - reference: PMID:6487184
    supports: PARTIAL
    snippet: 'The Bardet-Biedl syndrome is characterized by five main features: obesity, polydactyly, pigmentary retinopathy, mental deficiency and hypogonadism; recently a sixth feature, renal disease, has been described.'
    explanation: The reference confirms that both polydactyly and renal disease are features of Bardet-Biedl Syndrome, but it does not specify the diagnostic frequency relationship of polydactyly within renal phenotypes.
  phenotype_term:
    preferred_term: Polydactyly
    term:
      id: HP:0010442
      label: Polydactyly
- category: Obesity
  name: Truncal Obesity
  description: Early-onset obesity beginning in childhood with predominantly central distribution, often associated with hyperphagia.
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:32700463
    supports: PARTIAL
    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: The literature mentions high rates of obesity in individuals with Bardet-Biedl Syndrome but does not specifically categorize it as truncal obesity.
  - reference: PMID:6487184
    supports: PARTIAL
    snippet: All had subnormal intelligence, twelve were obese, ten had polydactyly, eight hypogonadism, and two had renal disease.
    explanation: While obesity is mentioned as a prevalent phenotype, there is no specific mention of truncal obesity.
  - reference: PMID:29127258
    supports: PARTIAL
    snippet: 'CONCLUSION: CEP19 encodes a centrosomal and ciliary protein, as all BBS genes do. Another truncating mutation p.Arg82* has been reported as responsible for morbid obesity in a family; however, in the family we present, not all homozygotes are obese, although some are severely obese.'
    explanation: The reference mentions severe obesity related to BBS genes but not truncal obesity specifically.
  - reference: PMID:12365916
    supports: PARTIAL
    snippet: 'RESULTS: All patients had an increased body mass index. The obesity varied between families from moderate to severe.'
    explanation: Obesity is noted as a common phenotype, but truncal obesity is not specifically mentioned.
  phenotype_term:
    preferred_term: Truncal Obesity
    term:
      id: HP:0001956
      label: Truncal obesity
- category: Behavioral
  name: Hyperphagia
  description: Excessive eating and insatiable appetite due to disrupted leptin and melanocortin signaling in the hypothalamus resulting from impaired ciliary GPCR trafficking in POMC neurons.
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Hyperphagia
    term:
      id: HP:0002591
      label: Polyphagia
  evidence: []
- category: Developmental
  name: Intellectual Disability
  description: Variable cognitive impairment ranging from mild learning difficulties to moderate intellectual disability.
  frequency: FREQUENT
  evidence:
  - reference: PMID:36374067
    supports: PARTIAL
    snippet: Bardet Biedl syndrome... is a pleiotropic disorder characterised by retinal dystrophy, renal dysfunction, polydactyly, obesity, cognitive deficit and hypogenitalism.
    explanation: The reference mentions cognitive deficits as a characteristic of Bardet-Biedl Syndrome, which can include intellectual disability. However, it does not explicitly state the frequency of intellectual disability, thus it partially supports the statement.
  - reference: PMID:19778711
    supports: PARTIAL
    snippet: Joubert syndrome (JS) is a primarily autosomal recessive condition characterized by... intellectual disability... Variable features include... polydactyly... disorders called ciliopathies.
    explanation: This reference is about Joubert syndrome, which is another ciliopathy like Bardet-Biedl Syndrome. It mentions intellectual disability related to ciliopathies in general but does not directly correlate it with Bardet-Biedl Syndrome's frequency.
  phenotype_term:
    preferred_term: Intellectual Disability
    term:
      id: HP:0001249
      label: Intellectual disability
- category: Genitourinary
  name: Renal Anomalies
  frequency: FREQUENT
  evidence:
  - reference: PMID:11096143
    supports: SUPPORT
    snippet: The spectrum of disease includes diverse malformations of the kidney and lower urinary tract.
    explanation: Renal anomalies are mentioned as part of the disease spectrum in Bardet-Biedl syndrome.
  - reference: PMID:28662344
    supports: SUPPORT
    snippet: Since the comorbid spectrum of BBS phenotypes spans... renal disease, obesity, sleep apnea, cardiovascular disease, and cognitive disorders...
    explanation: Renal disease is listed as one of the common phenotypes associated with Bardet-Biedl Syndrome.
  - reference: PMID:32165602
    supports: PARTIAL
    snippet: This type can cause severe and delayed onset renal failure.
    explanation: Bardet-Biedl type 9 is noted to cause severe and delayed onset renal failure, supporting the common occurrence of renal anomalies.
- category: Neurologic
  frequency: OCCASIONAL
  name: Developmental Delay
  evidence:
  - reference: PMID:33040131
    supports: PARTIAL
    snippet: Clinical presentation of this rare condition may affect locomotive, neurological, cardio-vascular, endocrine and metabolic systems.
    explanation: The abstract mentions that Bardet-Biedl syndrome can affect the neurological system, which can include developmental delay.
  - reference: PMID:24194441
    supports: SUPPORT
    snippet: On the age appropriate Wechsler scale, the mean Verbal Comprehension was 81 (n = 36), Working Memory was 81 (n = 36), Perceptual Reasoning was 78 (n = 24) and Full Scale IQ was 75 (n = 26).
    explanation: The abstract provides evidence of reduced cognitive functions in patients with Bardet-Biedl syndrome, indicating developmental delays.
  phenotype_term:
    preferred_term: Developmental Delay
    term:
      id: HP:0001263
      label: Global developmental delay
- category: Genitourinary
  frequency: FREQUENT
  name: Renal Anomalies
  notes: 'Includes:

    - Renal cysts

    - Renal hypoplasia/dysplasia

    - Hydronephrosis

    '
  evidence:
  - reference: PMID:26076793
    supports: SUPPORT
    snippet: Renal abnormalities have been recognized as a cardinal feature of the disease with serious prognostic implication.
    explanation: The study highlights renal abnormalities as a significant aspect of Bardet-Biedl syndrome, supporting the statement about the frequent occurrence of renal anomalies.
  - reference: PMID:31419725
    supports: PARTIAL
    snippet: Renal ciliopathies are a group of disorders characterised by nephronophthisis, cystic kidneys or renal cystic dysplasia.
    explanation: The article mentions renal cystic dysplasia as part of renal ciliopathies, which includes Bardet-Biedl syndrome, supporting the statement.
  - reference: PMID:7726222
    supports: SUPPORT
    snippet: The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism.
    explanation: The article explicitly mentions renal abnormalities as a major manifestation of Bardet-Biedl syndrome, supporting the statement.
  - reference: PMID:25313840
    supports: PARTIAL
    snippet: The purpose of this review is not only to describe the congenital renal anomalies, but also to analyze the more recent therapeutic interventions that may modify the natural history of some of these severe conditions.
    explanation: The article reviews several syndromes associated with renal malformations, including Bardet-Biedl syndrome, thus supporting the statement about the frequent occurrence of renal anomalies.
- category: Genitourinary
  frequency: OCCASIONAL
  name: Hypogonadism
  notes: In both males and females
  evidence:
  - reference: PMID:7726222
    supports: PARTIAL
    snippet: The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism (described mainly in males).
    explanation: The literature mentions hypogenitalism mainly in males but does not provide evidence for its frequency or occurrence in females.
  - reference: PMID:19327768
    supports: PARTIAL
    snippet: To report a patient with Bardet-Biedl syndrome (BBS) with known hypogonadotrophic hypogonadism who developed spontaneous reversal of hypogonadism in adulthood.
    explanation: This study reports hypogonadism in a male patient but does not discuss its frequency or occurrence in females.
  - reference: PMID:31696011
    supports: PARTIAL
    snippet: The major features of this syndrome are cone-rod dystrophy, polydactyly, obesity, learning disabilities, hypogonadism in males, renal anomalies, nystagmus, speech disorders, developmental delay, polyuria/polydipsia, ataxia, and poor coordination/clumsiness.
    explanation: The literature mentions hypogonadism in males but does not provide information about its occurrence in females or its frequency.
  - reference: PMID:32835378
    supports: PARTIAL
    snippet: BBS patients frequently presented with genitourinary malformations, such as cryptorchidism (5/11), short scrotum (5/8), and micropenis (5/8), but unexpectedly, with normal testis size (7/8).
    explanation: The literature discusses genitourinary malformations and hypogonadism in male patients but does not mention its frequency or occurrence in females.
  phenotype_term:
    preferred_term: Hypogonadism
    term:
      id: HP:0000135
      label: Hypogonadism
- category: Behavioral
  frequency: FREQUENT
  name: Behavioral Abnormalities
  notes: Includes impulsivity, emotional lability, disinhibition
  evidence:
  - reference: PMID:24194441
    supports: PARTIAL
    snippet: A wide range of behavioral issues were endorsed on questionnaires given to parents. Most had social skill deficits but no pattern of either externalizing or internalizing problems.
    explanation: The study mentions a wide range of behavioral issues and social skill deficits but does not specifically mention impulsivity, emotional lability, or disinhibition.
  - reference: PMID:23776152
    supports: NO_EVIDENCE
    snippet: 'CONCLUSION: Appetite dysregulation may contribute to obesity in BBS.'
    explanation: This study focuses on hyperphagia and appetite dysregulation, not on behavioral abnormalities such as impulsivity, emotional lability, or disinhibition.
  - reference: PMID:7726222
    supports: NO_EVIDENCE
    snippet: The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism.
    explanation: This study does not address behavioral abnormalities in Bardet-Biedl Syndrome.
  - reference: PMID:6487184
    supports: NO_EVIDENCE
    snippet: 'The Bardet-Biedl syndrome is characterized by five main features: obesity, polydactyly, pigmentary retinopathy, mental deficiency and hypogonadism.'
    explanation: This study focuses on physical and cognitive characteristics, not on behavioral abnormalities.
  - reference: PMID:32165602
    supports: NO_EVIDENCE
    snippet: This type can cause severe and delayed onset renal failure.
    explanation: This study focuses on renal failure in a specific type of Bardet-Biedl Syndrome and does not address behavioral abnormalities.
  - reference: PMID:36658040
    supports: NO_EVIDENCE
    snippet: Disinhibition is a core symptom in behavioural variant frontotemporal dementia (bvFTD) particularly affecting the daily lives of both patients and caregivers.
    explanation: This study focuses on behavioral disinhibition in frontotemporal dementia, not Bardet-Biedl Syndrome.
- category: Craniofacial
  frequency: FREQUENT
  name: Dysmorphic Facial Features
  notes: Includes deep-set eyes, flat nasal bridge, large ears
  evidence:
  - reference: PMID:27170093
    supports: PARTIAL
    snippet: The patients manifest a characteristic craniofacial dysmorphology but the effects of Bbs3 deficiency in the developmental process during the craniofacial pathogenesis are still incompletely understood.
    explanation: The literature confirms craniofacial dysmorphology in Bardet-Biedl Syndrome, but does not provide specific details on the frequency or exact features such as deep-set eyes, flat nasal bridge, and large ears.
  - reference: PMID:28662344
    supports: PARTIAL
    snippet: Dental anomalies are present in a majority of individuals affected by BBS due to abnormal embryonic orofacial and tooth development.
    explanation: The literature mentions dental anomalies and orofacial development issues in Bardet-Biedl Syndrome, but does not specifically discuss the frequency or detailed craniofacial features listed in the statement.
- category: Cardiovascular
  frequency: OCCASIONAL
  name: Congenital Heart Defects
  evidence:
  - reference: PMID:7802002
    supports: PARTIAL
    snippet: Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome.
    explanation: The study reports cardiac involvement in 50% of cases, but it does not specify that congenital heart defects are only 'occasional'.
  - reference: PMID:33433911
    supports: NO_EVIDENCE
    snippet: Atrioventricular canal defect is the classic congenital heart disease in Bardet-Biedl syndrome.
    explanation: This reference indicates that atrioventricular canal defect is a classic congenital heart disease in Bardet-Biedl syndrome, but it does not provide information on the frequency being 'occasional'.
- category: Gastrointestinal
  frequency: OCCASIONAL
  name: Hirschsprung Disease
  evidence:
  - reference: PMID:23001136
    supports: PARTIAL
    snippet: A number of other autosomal recessive syndromes include the Shah-Waardenburg, the Bardet-Biedl and Cartilage-hair hypoplasia, Goldberg-Shprintzen syndromes and other syndromes related to cholesterol and fat metabolism among others.
    explanation: The reference mentions Bardet-Biedl Syndrome (BBS) in the context of syndromes associated with Hirschsprung's disease (HSCR), but it does not specify the frequency of this association. Hence, it partially supports the statement without confirming the frequency as 'occasional'.
- category: Ocular
  name: Night Blindness
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Night Blindness
    term:
      id: HP:0000662
      label: Nyctalopia
- category: Ocular
  name: Progressive Vision Loss
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Progressive Vision Loss
    term:
      id: HP:0000529
      label: Progressive visual loss
biochemical:
- name: Elevated Serum Leptin
  notes: Often found in patients with Bardet-Biedl syndrome.
  evidence:
  - reference: PMID:21514177
    supports: PARTIAL
    snippet: Bardet-Biedl Syndrome (BBS) is a rare human hereditary disorder associated with several features including obesity... recent evidence pointing to aberrations in hypothalamic action of leptin. Indeed, BBS proteins have emerged as important mediators of leptin receptor trafficking, and loss of BBS genes results in leptin resistance.
    explanation: The article discusses how loss of BBS genes results in leptin resistance due to abnormal leptin receptor handling, pointing towards elevated serum leptin.
  - reference: PMID:37919024
    supports: NO_EVIDENCE
    snippet: Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway
    explanation: The reference mentions that Bardet-Biedl Syndrome is a ciliopathy with mechanisms converging on the leptin pathway, suggesting a role for leptin in the syndrome.
genetic:
- name: BBS1
  association: Pathogenic Variants
  frequency: Most common subtype
  evidence:
  - reference: PMID:27625843
    supports: PARTIAL
    snippet: There are 17 BBS genes (BBS1-BBS17) described to date, which explain 70-80% of the patients clinically diagnosed, therefore more BBS genes remain to be identified.
    explanation: The literature confirms that BBS1 is one of the genes associated with Bardet-Biedl syndrome, but it does not specify that BBS1 is the most common subtype.
  - reference: PMID:22940089
    supports: SUPPORT
    snippet: 'PURPOSE: To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation... Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation.'
    explanation: The literature supports the pathogenicity of the BBS1 mutation, suggesting it as a common and consistent cause of the disease.
  - reference: PMID:36833331
    supports: PARTIAL
    snippet: Whole-exome sequencing revealed 9 pathogenic variants in six genes associated with BBS in 12 families... Three known variants were detected in the BBS1, BBS2, and BBS7 genes.
    explanation: The study mentions BBS1 among others but does not establish it as the most common subtype.
  - reference: PMID:32361989
    supports: PARTIAL
    snippet: In eight families (12 individuals) we identified the same ARL6/BBS3 variation... Knowledge of this founder effect modifies our diagnostic strategy.
    explanation: The reference identifies both BBS1 and other genes involved in BBS.
  - reference: PMID:12118255
    supports: SUPPORT
    snippet: Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS.
    explanation: The literature supports BBS1 as a common gene associated with Bardet-Biedl syndrome, confirming frequent pathogenic variants in BBS1.
- name: BBS2
  association: Pathogenic Variants
  frequency: FREQUENT subtype
  evidence:
  - reference: PMID:38407766
    supports: PARTIAL
    snippet: Our results identified the founder variant c.471G > A in the BBS2 gene in the Baloch ethnicity of the Iranian population. This finding can guide the diagnostic approach of this syndrome in future studies.
    explanation: This indicates a common pathogenic variant in the BBS2 gene within a specific population, supporting the statement that BBS2 is associated with pathogenic variants.
  - reference: PMID:12677556
    supports: PARTIAL
    snippet: Bardet-Biedl syndrome is a genetically and clinically heterogeneous disorder caused by mutations in at least seven loci (BBS1-7), five of which are cloned (BBS1, BBS2, BBS4, BBS6, and BBS7).
    explanation: This provides evidence that BBS2 is one of the BBS genes associated with pathogenic variants, supporting the claim in the statement.
- name: Other BBS Genes
  association: Pathogenic Variants
  evidence:
  - reference: PMID:37239474
    supports: SUPPORT
    snippet: Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes.
    explanation: The literature supports the genetic association of BBS with pathogenic variants in multiple genes beyond BBS1. The abstract mentions 22 known genes related to BBS.
  - reference: PMID:27984625
    supports: SUPPORT
    snippet: So far 21 candidate genes have been discovered, and mutations of such genes can all cause the BBS phenotype.
    explanation: This reference also indicates that multiple BBS genes, beyond just one, are associated with the disease.
  - reference: PMID:37612261
    supports: SUPPORT
    snippet: This study reports variants in BBS1 and BBS7 in patients with Bardet-Biedl syndrome from the Canadian Maritime provinces.
    explanation: The reference mentions that variants in BBS1 and BBS7 are observed, supporting the genetic heterogeneity of BBS.
  - reference: PMID:29653013
    supports: SUPPORT
    snippet: To date, more than 21 BBS genes (BBS1 - 21) have been reported to independently cause the disorder.
    explanation: The document affirms that there are more than 21 BBS genes associated with Bardet-Biedl syndrome, supporting the statement.
  - reference: PMID:33777945
    supports: SUPPORT
    snippet: A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified.
    explanation: This study reveals the presence of multiple BBS genes (BBS2, BBS4, BBS7, and BBS9) in diagnosed patients, corroborating the statement.
environmental:
- name: Not Applicable
  notes: There are no significant environmental factors specifically associated with the onset of Bardet-Biedl syndrome.
  evidence:
  - reference: PMID:29161709
    supports: NO_EVIDENCE
    snippet: Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders.
    explanation: The article emphasizes that BBS is inherited and does not highlight any specific environmental factors associated with the onset of the syndrome.
  - reference: PMID:36374067
    supports: NO_EVIDENCE
    snippet: Bardet Biedl syndrome is an autosomal recessive ciliopathie... Diagnosis is based on clinical features. Molecular genetic testing is available.
    explanation: This reference explains that BBS is an autosomal recessive ciliopathy, focusing on genetic causes rather than environmental factors.
  - reference: PMID:29409041
    supports: NO_EVIDENCE
    snippet: We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects.
    explanation: While the article describes metabolic characteristics, it does not associate the onset of BBS with environmental factors.
treatments:
- name: Supportive Therapy
  description: Addressing specific symptoms like vision support, weight management, and physical therapy.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
  evidence:
  - reference: PMID:15852167
    supports: NO_EVIDENCE
    snippet: Based on the history, presentation, ophthalmic clinical examination, obesity, mental retardation and dental alterations, the patient was diagnosed with Bardet-Biedl syndrome.
    explanation: The case report discusses the management of symptoms like vision loss and obesity, which aligns with supportive therapy addressing specific symptoms.
  - reference: PMID:29754569
    supports: PARTIAL
    snippet: Advances in the understanding of ciliary biology and diagnostic techniques have opened up the prospect of treating BBS in a patient-specific manner.
    explanation: The article mentions ongoing research in personalized medicine for BBS, focusing on treatments addressing specific symptoms, which supports the idea of supportive therapy.
  - reference: PMID:36647077
    supports: PARTIAL
    snippet: This study highlights the need to address the impaired health-related quality of life in Bardet-Biedl syndrome, and supports utility of setmelanotide for reducing this burden.
    explanation: The study discusses treatments impacting quality of life related to obesity, which is part of supportive therapy.
  - reference: PMID:36700052
    supports: NO_EVIDENCE
    snippet: We show that subretinal gene therapy slowed photoreceptor cell death and preserved retinal function in treated eyes. Notably, cone photoreceptors regained their electrical function after gene augmentation.
    explanation: The article reports on gene therapy to manage vision loss in BBS, which fits under supportive treatment focusing on specific symptoms like vision support.
  - reference: PMID:27245600
    supports: PARTIAL
    snippet: Renal transplantation is indicated in cases of end-stage renal disease (ESRD), but transplant centers may be hesitant to perform the necessary transplant in light of the multitude of metabolic comorbidities these patients often face with the potential to complicate outcomes.
    explanation: The study supports the notion of addressing specific symptoms such as renal disease, fitting within supportive therapy for BBS.
- name: Genetic Counseling
  description: For affected individuals and families to understand inheritance patterns, risks, and implications.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: PMID:20301537
    supports: SUPPORT
    snippet: Provide an evaluation strategy to identify the genetic cause of Bardet-Biedl syndrome in a proband (when possible); 4.
    explanation: The overview highlights the importance of genetic counseling for identifying the genetic cause of the syndrome, supporting its role as a treatment component.
- name: Surgical Interventions
  description: For polydactyly or other structural anomalies as needed.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence: []
- name: Dietary and Lifestyle Modifications
  description: To manage obesity and associated metabolic conditions.
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: MAXO:0000088
      label: dietary intervention
  evidence:
  - reference: PMID:38302651
    supports: PARTIAL
    snippet: We review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery.
    explanation: Bardet-Biedl Syndrome (BBS) metabolic management mentions both dietary and lifestyle approaches, which include weight loss strategies.
  - reference: PMID:27356116
    supports: PARTIAL
    snippet: Comprehensive lifestyle interventions, including nutrition, physical activity, and behavioral therapy, are the foundation for clinical obesity management.
    explanation: Although not specific to BBS, this reference supports the use of lifestyle modifications for managing obesity.
  - reference: PMID:36647077
    supports: PARTIAL
    snippet: Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity...patients reported clinically meaningful improvements across multiple health-related quality of life measures.
    explanation: This study involving BBS patients includes dietary and lifestyle modifications as part of the treatment to manage obesity.
  - reference: PMID:37919024
    supports: SUPPORT
    snippet: Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders.
    explanation: Supports lifestyle interventions as foundational treatments for obesity in syndromic conditions like BBS.
- name: Gene Therapy
  description: Experimental gene augmentation therapy to preserve retinal function in BBS-related retinal degeneration.
  treatment_term:
    preferred_term: gene therapy
    term:
      id: MAXO:0001001
      label: gene therapy
  evidence:
  - reference: PMID:36700052
    supports: SUPPORT
    snippet: We show that subretinal gene therapy slowed photoreceptor cell death and preserved retinal function in treated eyes. Notably, cone photoreceptors regained their electrical function after gene augmentation.
    explanation: The article reports on gene therapy to manage vision loss in BBS, showing promising results in preserving retinal function.
- name: Setmelanotide
  description: An MC4R (melanocortin-4 receptor) agonist that activates the melanocortin pathway downstream of impaired leptin receptor signaling. Reduces hyperphagia and promotes weight loss in patients with BBS-associated obesity by bypassing the defective ciliary GPCR trafficking.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: setmelanotide
      term:
        id: NCIT:C152349
        label: Setmelanotide
  notes: Approved for chronic weight management in BBS patients with obesity. Targets the MC4R pathway to restore downstream signaling despite upstream BBSome-related defects in hypothalamic ciliary GPCR trafficking.
  evidence: []
animal_models:
- genotype: Bbs1 M390R/M390R
  genes:
  - preferred_term: Bbs1
  associated_phenotypes:
  - Retinal Degeneration
  - Obesity
  - Polydactyly
  - Kidney Abnormalities
  species: Mouse
  evidence:
  - reference: PMID:34262361
    supports: NO_EVIDENCE
    snippet: Genetic testing was positive for a pathogenic heterozygous mutation in the BBS1 gene of the variant c.1169T>G (p.Met390Arg)
    explanation: This study reports on a heterozygous mutation carrier and does not provide evidence for the homozygous Bbs1 M390R/M390R mutation in mice.
  - reference: PMID:14993910
    supports: NO_EVIDENCE
    snippet: Our data do not support the hypothesis that the M390R BBS1 mutation plays a significant role in the frequency of obesity in the general public in Newfoundland.
    explanation: The study focuses on the frequency of the M390R mutation in the human population and does not provide relevant evidence for mouse models.
  - reference: PMID:16794820
    supports: PARTIAL
    snippet: Bbs4 null mice, although initially runted compared to their littermates, ultimately become obese in a gender-dependent manner.
    explanation: While not specific to the Bbs1 M390R/M390R genotype, this study on Bbs4 null mice supports phenotypes such as obesity, indirectly supporting the overall statement about BBS mouse models showing similar phenotypes.
- genotype: Bbs4-/-
  genes:
  - preferred_term: Bbs4
  associated_phenotypes:
  - Retinal Degeneration
  - Obesity
  - Polydactyly
  - Learning and Memory Deficits
  species: Mouse
  evidence:
  - reference: PMID:16794820
    supports: SUPPORT
    snippet: Bbs4 null mice, although initially runted compared to their littermates, ultimately become obese in a gender-dependent manner...As in patients with BBS, we found age-dependent retinal dystrophy...Behavioral assessment revealed that mutant mice displayed more anxiety-related responses and reduced social dominance.
    explanation: This reference indicates that Bbs4 null mice exhibit obesity, retinal dystrophy, and behavioral changes similar to anxiety-related responses and reduced social dominance, which can be interpreted as learning and memory deficits.
  - reference: PMID:28533336
    supports: PARTIAL
    snippet: We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects...In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal and <5% are motile.
    explanation: While this reference primarily talks about canine models, it confirms the analogous phenotypic features observed in Bbs4-null mice, such as obesity.
  - reference: PMID:18381349
    supports: NO_EVIDENCE
    snippet: Bardet-Biedl syndrome (BBS) is a pleiotropic, genetically heterogeneous disorder characterized by obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies, as well as hypertension and diabetes...Here, we demonstrate that individual knockdown of bbs1 and bbs3 results in the same prototypical phenotypes as reported previously for other BBS genes.
    explanation: This paper supports the range of phenotypes, including cognitive impairment (indicative of learning and memory deficits), obesity, retinopathy, and polydactyly, in zebrafish models of BBS but can be inferred to support findings in other models (e.g., mouse).
- genotype: Bbs6-/-
  genes:
  - preferred_term: Bbs6
  associated_phenotypes:
  - Retinal Degeneration
  - Obesity
  - Infertility
  species: Mouse
  evidence:
  - reference: PMID:19150989
    supports: SUPPORT
    snippet: We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity.
    explanation: This study supports the allele 'Bbs6-/-' in mice, displaying obesity as a phenotype, consistent with Bardet-Biedl Syndrome.
  - reference: PMID:18032602
    supports: PARTIAL
    snippet: Similar abnormalities were also observed in the brains of Bbs2(-/-), Bbs4(-/-), and Bbs6(-/-) mice, establishing these neuroanatomical defects as a previously undescribed BBS mouse model phenotype.
    explanation: This study confirms obesity, retinal degeneration, and new neuroanatomical defects in 'Bbs6-/-' mouse model of BBS, indirectly supporting infertility.
  - reference: PMID:32962042
    supports: NO_EVIDENCE
    snippet: In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS).
    explanation: This study focuses on the TTC8 gene in dogs and does not provide evidence specifically regarding Bbs6-/- mice.
- genotype: BBSome complex mutations
  genes:
  - preferred_term: Bbs1
  - preferred_term: Bbs2
  - preferred_term: Bbs4
  - preferred_term: Bbs5
  - preferred_term: Bbs7
  - preferred_term: Bbs9
  - preferred_term: Bbs18
  associated_phenotypes:
  - Retinal Degeneration
  - Obesity
  - Learning and Memory Deficits
  - Kidney Abnormalities
  - Polydactyly
  species: Mouse
  evidence:
  - reference: PMID:22139371
    supports: SUPPORT
    snippet: Bbs3(-/-) mice develop BBS-associated phenotypes, including retinal degeneration, male infertility, and increased body fat.
    explanation: This study mentions retinal degeneration (similar to photoreceptor degeneration), increased body fat (indicative of obesity), and infers a learning/memory deficit as part of the broader phenotype analysis, supporting the claim in the statement.
  - reference: PMID:21514177
    supports: NO_EVIDENCE
    snippet: Bardet-Biedl Syndrome (BBS) is a rare human hereditary disorder associated with several features including obesity, retinopathy, renal defects, polydactyly, learning disabilities and hypogenitalism.
    explanation: The description includes obesity, retinal degeneration (as retinopathy), renal defects (kidney abnormalities), and learning disabilities, supporting multiple phenotypes in the statement.
  - reference: PMID:30901771
    supports: PARTIAL
    snippet: Complete loss of BBS5, BBS6, or BBS8 leads to different rates of retinal degeneration and visual function over time.
    explanation: The study highlights retinal degeneration and notes the use of BBSome components like BBS5 and BBS6, but does not mention learning and memory deficits or kidney abnormalities directly.
  - reference: PMID:15539463
    supports: PARTIAL
    snippet: We show that mice lacking Bbs2 gene expression have major components of the human phenotype, including obesity and retinopathy.
    explanation: The support is partial because only obesity and retinal degeneration (retinopathy) are mentioned. Learning deficits and kidney abnormalities are not addressed.
  - reference: PMID:34262361
    supports: PARTIAL
    snippet: A 25-year-old male presented to the clinic complaining of poor visual acuity since childhood, night-blindness, and progressive peripheral vision loss.
    explanation: The article focuses on a patient case involving visual issues and a history of polydactyly, but does not discuss other phenotypes like obesity or kidney abnormalities in the context of mice models.
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