Syndromic Obesity Ciliopathy

name	description	evidence
BBS1	The most common subtype caused by mutations in the BBS1 gene.	TRUNCATED
BBS2	Caused by mutations in the BBS2 gene, associated with similar features but can show some phenotypic variability.	TRUNCATED
Other BBS Subtypes	Caused by mutations in various other BBS genes, including BBS3, BBS4, BBS5, and more.	TRUNCATED

0

population

Global

percentage

0.00001-0.00003

evidence

reference	supports	snippet	explanation
PMID:22109794	PARTIAL	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.	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).
PMID:37137806	NO_EVIDENCE	AIMS: We described the updated global IBD epidemiology results based on the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD).	This paper deals with inflammatory bowel disease (IBD) and provides no direct evidence about the global prevalence of Bardet-Biedl Syndrome.

0

name

Ciliary Dysfunction

description

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

evidence

reference	supports	snippet	explanation
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	SUPPORT	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.	This reference emphasizes the role of primary cilia dysfunction in BBS and its association with retinal dystrophies, supporting the statement.
PMID:33511755	SUPPORT	Bardet-Biedl syndrome (BBS) is a genetic disorder caused by the dysfunction of the primary cilium.	This excerpt clearly states that BBS is caused by primary cilium dysfunction, aligning with the statement.
PMID:33560420	SUPPORT	Defects in ciliary structure and signaling result in a broad group of disorders collectively known as ciliopathies. One ciliopathy, Bardet-Biedl syndrome (BBS), 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.
PMID:21477661	SUPPORT	Genetic causes of obesity include the ciliopathies Alstrom syndrome and Bardet-Biedl syndrome. In these disorders, mutations cause dysfunction of the primary cilium, an organelle involved in intracellular and intercellular sensing and signaling.	This reference further reinforces the statement by associating the dysfunction of primary cilia due to genetic mutations with BBS.

cellular_components

• Primary Cilium

0

category

Ophthalmologic

name

Retinitis Pigmentosa

frequency

VERY_FREQUENT

diagnostic

True

sequelae

Night Blindness Progressive Vision Loss

evidence

reference	supports	snippet	explanation
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	SUPPORT	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.
PMID:31864384	SUPPORT	Inherited retinal dystrophies are major cause of severe progressive vision loss in children.	Retinal dystrophies, including RP, are significant causes of progressive vision loss, congruent with the statement's listed sequelae.

1

category

Renal

name

Polydactyly

frequency

FREQUENT

diagnostic

True

evidence

reference	supports	snippet	explanation
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.

2

category

Obesity

name

Truncal Obesity

frequency

VERY_FREQUENT

evidence

reference	supports	snippet	explanation
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.
PMID:12365916	PARTIAL	RESULTS: All patients had an increased body mass index. The obesity varied between families from moderate to severe.	Obesity is noted as a common phenotype, but truncal obesity is not specifically mentioned.

3

category

Developmental

name

Intellectual Disability

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
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.

4

category

Genitourinary

name

Renal Anomalies

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
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:20301537	SUPPORT	Bardet-Biedl syndrome is a clinically variable condition associated with... cystic and fibrotic renal changes that can lead to renal failure.	Renal anomalies are highlighted, including cystic and fibrotic changes leading to renal failure.
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	SUPPORT	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.

name	evidence	notes
Elevated Serum Leptin	TRUNCATED	Often found in patients with Bardet-Biedl syndrome.

0

name

BBS1

evidence

reference	supports	snippet	explanation
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.
PMID:32361989	PARTIAL	In eight families (12 individuals) we identified the same ARL6/BBS3 variation... Knowledge of this founder effect modifies our diagnostic strategy.	The reference identifies both BBS1 and other genes involved in BBS.
PMID:12118255	SUPPORT	Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS.	The literature supports BBS1 as a common gene associated with Bardet-Biedl syndrome, confirming frequent pathogenic variants in BBS1.

association

Pathogenic Variants

frequency

Most common subtype

1

name

BBS2

evidence

reference	supports	snippet	explanation
PMID:38407766	SUPPORT	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	SUPPORT	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.

association

Pathogenic Variants

frequency

FREQUENT subtype

2

name

Other BBS Genes

evidence

reference	supports	snippet	explanation
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.
PMID:29653013	SUPPORT	To date, more than 21 BBS genes (BBS1 - 21) have been reported to independently cause the disorder.	The document affirms that there are more than 21 BBS genes associated with Bardet-Biedl syndrome, supporting the statement.
PMID:33777945	SUPPORT	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.	This study reveals the presence of multiple BBS genes (BBS2, BBS4, BBS7, and BBS9) in diagnosed patients, corroborating the statement.

association

Pathogenic Variants

0

name

Not Applicable

evidence

reference	supports	snippet	explanation
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:24611592	NO_EVIDENCE	The purpose of this overview is to increase the awareness of clinicians regarding the causes of Bardet-Biedl syndrome and related genetic counseling issues.	The reference mentions genetic counseling and causes but does not address environmental factors being significant for BBS.
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.

notes

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

0

name

Supportive Therapy

description

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

evidence

reference	supports	snippet	explanation
PMID:15852167	SUPPORT	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	SUPPORT	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	SUPPORT	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.
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, which fits under supportive treatment focusing on specific symptoms like vision support.
PMID:27245600	SUPPORT	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.	The study supports the notion of addressing specific symptoms such as renal disease, fitting within supportive therapy for BBS.
PMID:21209035	SUPPORT	Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder of the primary cilium associated with obesity.	The article confirms obesity as a significant symptom treated in BBS cases, aligning with supportive therapy focused on weight management.

1

name

Genetic Counseling

description

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

evidence

reference	supports	snippet	explanation
PMID:20301537	SUPPORT	Bardet-Biedl syndrome and related genetic counseling issues. [...] Provide an evaluation strategy to identify the genetic cause of Bardet-Biedl syndrome in a proband (when possible).	The overview highlights the importance of genetic counseling for identifying the genetic cause of the syndrome, supporting its role as a treatment component.
PMID:29754569	SUPPORT	Variations in recurrence risks [...] may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options.	The study discusses recurrence risks and their relevance for genetic counseling, directly aligning with the statement.

2

name

Surgical Interventions

description

For polydactyly or other structural anomalies as needed.

evidence

reference	supports	snippet	explanation
PMID:30293640	PARTIAL	Surgical revisions can be necessary for structural anomalies, including polydactyly.	The literature mentions interventions for structural anomalies but does not specifically emphasize surgical interventions for these cases only.
PMID:28662344	PARTIAL	The genetic impact of BBS on the anatomic development of oral components and the broad spectrum of collateral oral disease may necessitate specialized management, including potential surgical interventions.	This reference discusses the necessity for managing structural anomalies which may include surgical interventions but does not explicitly name polydactyly as the only condition warranting surgery.
PMID:23692385	PARTIAL	Clinical features and genetic results observed in a pair of dizygotic twins with BBS included retinitis pigmentosa, bilateral insertional polydactyly, cognitive impairment, and renal dysfunction.	While polydactyly is frequently mentioned, this literature does not explicitly discuss surgical interventions as a treatment.

3

name

Dietary and Lifestyle Modifications

description

To manage obesity and associated metabolic conditions.

evidence

reference	supports	snippet	explanation
PMID:38302651	SUPPORT	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	SUPPORT	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	SUPPORT	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.
PMID:37919024	SUPPORT	Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders.	Supports lifestyle interventions as foundational treatments for obesity in syndromic conditions like BBS.

name	evidence
Autosomal recessive	TRUNCATED

species	genotype	genes	associated_phenotypes
Mouse	Bbs1 M390R/M390R	Bbs1	Retinal Degeneration Obesity Polydactyly Kidney Abnormalities
Mouse	Bbs4-/-	Bbs4	Retinal Degeneration Obesity Polydactyly Learning and Memory Deficits
Mouse	Bbs6-/-	Bbs6	Retinal Degeneration Obesity Infertility
Mouse	BBSome complex mutations	Bbs1 Bbs2 Bbs4 Bbs5 Bbs7 Bbs9 Bbs18	Retinal Degeneration Obesity Learning and Memory Deficits Kidney Abnormalities Polydactyly