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European Journal of Human Genetics :... Jan 2013Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterised by retinal dystrophy, obesity, post-axial polydactyly, renal dysfunction, learning...
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterised by retinal dystrophy, obesity, post-axial polydactyly, renal dysfunction, learning difficulties and hypogonadism. Many associated minor features can be helpful in making a diagnosis and are important in the clinical management of BBS. The diagnosis is based on clinical findings and can be confirmed by sequencing of known disease-causing genes in 80% of patients. BBS genes encode proteins that localise to the cilia and basal body and are involved in cilia biogenesis and function. Mutations lead to defective cilia accounting in part for the pleiotropic effects observed in BBS. We provide an overview of BBS including the clinical findings, current understanding of cilia biology, and a practical approach to diagnosis, genetic counselling and up-to-date management.
Topics: Bardet-Biedl Syndrome; Chaperonins; Genetic Association Studies; Genetic Counseling; Genetic Testing; Group II Chaperonins; Humans; Microtubule-Associated Proteins; Mutation; Proteins
PubMed: 22713813
DOI: 10.1038/ejhg.2012.115 -
Advances in Experimental Medicine and... 2018Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious... (Review)
Review
Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious by 6 years of age). About two thirds of patients have postaxial polydactyly, and sometimes syndactyly, brachydactyly, and/or clinodactyly may be present. Hypogonadism and renal involvement occur in about 40%, mental retardation in about 50%, and truncal obesity in about 70%; it is present early, along with insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Vision becomes markedly impaired by about age 30 years. The BBS is genetically heterogeneous entity with considerable phenotypic variability. Other associated problems include CNS-related ataxia, abnormal gait, and facial hypotonia, as well as anomalies such as high palate, hearing loss, and cardiac malformations. In males, there is oligospermia, leading to infertility. Around 50–80% of BBS patients have renal malformations (like cyst, agenesis or scarring) and renal dysfunction leading to end-stage renal disease. There are no pigmentary changes before the age of 1–2 years. Later, subtle pigmentary changes appear in the macula or peripapillary area. Several years later, pigments appear in the equatorial region, along with attenuation of retinal blood vessels and waxy pallor of the optic disc. Eventually, the macula may show atrophic changes (Figs. 33.1, 33.2 and 33.3). Electroretinography (ERG) shows involvement of rods and cones and is abnormal even before the fundus shows changes. A perimacular hyperfluorescent ring can be seen.
Topics: Bardet-Biedl Syndrome; Diabetes Mellitus, Type 2; Electroretinography; Female; Humans; Intellectual Disability; Male; Polydactyly
PubMed: 30578506
DOI: 10.1007/978-3-319-95046-4_33 -
Genes Aug 2021Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely... (Review)
Review
Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet-Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.
Topics: Bardet-Biedl Syndrome; Fingers; Genetic Association Studies; Genetic Pleiotropy; Humans; Microtubule-Associated Proteins; Mutation; Polydactyly; Protein Interaction Maps; Toes
PubMed: 34573333
DOI: 10.3390/genes12091353 -
Current Opinion in Endocrinology,... Feb 2023Bardet Biedl syndrome (BBS) is a rare disease characterized by obesity and hyperphagia. Despite the very high prevalence of paediatric and adult obesity in this... (Review)
Review
PURPOSE OF REVIEW
Bardet Biedl syndrome (BBS) is a rare disease characterized by obesity and hyperphagia. Despite the very high prevalence of paediatric and adult obesity in this population, the prevalence of diabetes mellitus is not well described.
RECENT FINDINGS
Studies in small and moderately large cohorts suggest a high prevalence of traditional risk factors for diabetes mellitus in people with BBS. People with BBS appear to have a high prevalence of insulin resistance and metabolic syndrome. Small cohort studies have identified high rates of sleep disordered breathing, including sleep apnoea syndrome. Recent research has characterized traditional behavioural risk factors such as sleep hygiene and physical inactivity in people with BBS. High rates of insufficient sleep and prolonged sedentary time suggest behavioural targets of interventions to treat or prevent diabetes mellitus. Hyperphagia, likely caused by defects in the hypothalamic melanocortin-4 receptor (MC4R) neuronal pathway, pose additional challenges to behavioural interventions to prevent diabetes mellitus.
SUMMARY
Understanding the prevalence of diabetes mellitus and other metabolic disorders in people with BBS and the impact of traditional risk factors on glucose regulation are important to developing effective treatments in this population.
Topics: Adult; Humans; Child; Bardet-Biedl Syndrome; Diabetes Mellitus; Obesity; Metabolic Syndrome; Hyperphagia
PubMed: 36476576
DOI: 10.1097/MED.0000000000000788 -
Journal of Medical Case Reports Apr 2022Bardet-Biedl syndrome is a rare multisystem autosomal recessive disorder that falls under the spectrum of ciliopathy disorders. It is characterized by rod-cone...
BACKGROUND
Bardet-Biedl syndrome is a rare multisystem autosomal recessive disorder that falls under the spectrum of ciliopathy disorders. It is characterized by rod-cone dystrophy, renal malformations, polydactyly, learning difficulties, central obesity, and hypogonadism. Many minor features that are related with Bardet-Biedl syndrome might aid in diagnosis and are crucial in clinical management. Bardet-Biedl syndrome is diagnosed on the basis of clinical signs and symptoms, which can be confirmed by genetic testing. Here we present four cases of Bardet-Biedl syndrome. To our knowledge, these are the first cases of Bardet-Biedl syndrome reported from Sudan.
CASE PRESENTATION
Here, we report four Sudanese patients who presented with a variety of clinical manifestations of Bardet-Biedl syndrome (two males, 50 and 16 years old; two females, 38 and 18 years old). The first two patients presented with features of chronic kidney disease. The third patient had recently been diagnosed with type 1 diabetes and diabetic ketoacidosis. The fourth patient showed signs of retinal dystrophy early on. Case 1: a 38-year-old female presented with vomiting and irritability; the patient was diagnosed with Bardet-Biedl syndrome as she fulfilled six items of the primary features (obesity, retinitis pigmentosa, post-axial polydactyly, renal abnormalities, learning disabilities, and genitourinary malformations), as well as one secondary feature (cardiovascular involvement, that is, left ventricular hypertrophy). Case 2: a 50-year-old male presented with fatigability; the patient was diagnosed with Bardet-Biedl syndrome as he fulfilled four items of the primary features (obesity, retinitis pigmentosa, post-axial polydactyly, and renal abnormalities) in addition to two secondary features (diabetes mellitus and cardiovascular involvement, that is, left ventricular hypertrophy). Case 3: an 18-year-old female presented with polyuria, polydipsia, weight loss, and epigastric pain for 2 days; the patient was diagnosed with Bardet-Biedl syndrome because he had four major features (retinal dystrophy, post-axial polydactyly, obesity, and learning disabilities) in addition to three secondary features (developmental delay, diabetes mellitus, and strabismus). Case 4: a 16-year-old male presented with a blurring of vision; the patient was diagnosed with Bardet-Biedl syndrome as he exhibited four major features (retinal dystrophy, post-axial polydactyly, obesity, and learning disabilities) plus two secondary features (developmental delay and cataract).
CONCLUSION
The scarcity of Bardet-Biedl syndrome necessitates a high index of suspicion to diagnose this syndrome. Increased awareness among physicians is required for the early diagnosis and treatment of Bardet-Biedl syndrome and to avoid complications and mortality.
Topics: Adolescent; Adult; Bardet-Biedl Syndrome; Female; Fingers; Humans; Hypertrophy, Left Ventricular; Kidney; Learning Disabilities; Male; Middle Aged; Obesity; Polydactyly; Retinitis Pigmentosa; Toes; Urogenital Abnormalities
PubMed: 35484558
DOI: 10.1186/s13256-022-03396-6 -
American Journal of Medical Genetics.... Mar 2022Bardet-Biedl syndrome (BBS) is a rare pleiotropic disorder known as a ciliopathy. Despite significant genetic heterogeneity, BBS1 and BBS10 are responsible for major... (Review)
Review
Bardet-Biedl syndrome (BBS) is a rare pleiotropic disorder known as a ciliopathy. Despite significant genetic heterogeneity, BBS1 and BBS10 are responsible for major diagnosis in western countries. It is well established that eight BBS proteins, namely BBS1, 2, 4, 5, 7, 8, 9, and 18, form the BBSome, a multiprotein complex serving as a regulator of ciliary membrane protein composition. Less information is available for BBS6, BBS10, and BBS12, three proteins showing sequence homology with the CCT/TRiC family of group II chaperonins. Even though their chaperonin function is debated, scientific evidence demonstrated that they are required for initial BBSome assembly in vitro. Recent studies suggest that genotype may partially predict clinical outcomes. Indeed, patients carrying truncating mutations in any gene show the most severe phenotype; moreover, mutations in chaperonin-like BBS proteins correlated with severe kidney impairment. This study is a critical review of the literature on genetics, expression level, cellular localization and function of BBS proteins, focusing primarily on the chaperonin-like BBS proteins, and aiming to provide some clues to understand the pathomechanisms of disease in this setting.
Topics: Bardet-Biedl Syndrome; Chaperonins; Group II Chaperonins; Humans; Mutation
PubMed: 35373910
DOI: 10.1002/ajmg.c.31970 -
FEBS Letters Nov 2015Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic disorder, characterized by both congenital and late onset defects. From the analysis of the... (Review)
Review
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic disorder, characterized by both congenital and late onset defects. 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. Here we briefly review the genetics of BBS to then focus on the function of the BBS proteins, not only in the context of the cilium but also highlighting potential extra-ciliary roles that could be relevant to the etiology of the disorder. Finally, we provide an overview of how the study of this rare syndrome has contributed to the understanding of cilia biology and how this knowledge has informed on the cellular basis of different clinical manifestations that characterize BBS and the ciliopathies.
Topics: Animals; Bardet-Biedl Syndrome; Cilia; Humans; Phenotype; Proteins
PubMed: 26231314
DOI: 10.1016/j.febslet.2015.07.031 -
Personalized Medicine Sep 2017Personalized medicine is becoming routine in the treatment of common diseases such as cancer, but has lagged behind in the field of rare diseases. It is currently in the... (Review)
Review
Personalized medicine is becoming routine in the treatment of common diseases such as cancer, but has lagged behind in the field of rare diseases. It is currently in the early stages for the treatment of Bardet-Biedl syndrome. Advances in the understanding of ciliary biology and diagnostic techniques have opened up the prospect of treating BBS in a patient-specific manner. Owing to their structure and function, cilia provide an attractive therapeutic target and genetic therapies are being explored in ciliopathy treatment. Promising avenues include gene therapy, gene editing techniques and splice-correcting and read-through therapies. Targeted drug design has been successful in the treatment of genetic disease and research is underway in the discovery of known and novel drugs to treat Bardet-Biedl syndrome.
Topics: Bardet-Biedl Syndrome; Cilia; Genetic Therapy; Humans; Pharmacogenetics; Precision Medicine
PubMed: 29754569
DOI: 10.2217/pme-2017-0019 -
Annales D'endocrinologie Dec 2008Bardet-Biedl syndrome (BBS) is a ciliopathy causing multivisceral abnormalities. Its prevalence in Europe is from 1/125,000 to 1/175,000. This disorder is defined by a... (Review)
Review
Bardet-Biedl syndrome (BBS) is a ciliopathy causing multivisceral abnormalities. Its prevalence in Europe is from 1/125,000 to 1/175,000. This disorder is defined by a combination of clinical signs: obesity, pigmentary retinopathy, post-axial polydactyly, polycystic kidneys, hypogenitalism, and learning disabilities, many of which appearing after several years of evolution. Individual clinical phenotype is highly variable. Most signs are present in a majority of patients but only pigmentary retinopathy is constant after infancy. There are many other associated minor clinical signs including diabetes, blood hypertension, congenital cardiopathy or Hirschsprung disease. This broad clinical spectrum is associated to a great genetic heterogeneity, with mainly an autosomal recessive transmission and, sometimes cases of oligogenism. To date, mutations in 12 different genes (BBS1 to BBS12) are responsible for this phenotype. These genes code for proteins involved in the development and function of primary cilia. Absent or non functional BBS proteins affect cilia in certain organs such as kidney or eye. However, some symptoms are still not clearly related to cilia dysfunction. BB syndrome has to be recognized because a molecular diagnosis is possible and will lead to familial genetic counseling and possibly prenatal diagnosis. Patients with BBS will need a multidisciplinary medical care. The renal abnormalities are the main life-threatening features because they can lead to end-stage renal failure and renal transplantation. Retinal dystrophy leading to progressive vision loss, moderate mental retardation, and obesity will affect social life of these patients.
Topics: Bardet-Biedl Syndrome; Diagnosis, Differential; Genetic Counseling; Humans; Prenatal Diagnosis; Prognosis
PubMed: 19019343
DOI: 10.1016/j.ando.2008.10.001 -
Clinical Genetics Apr 2022The aim of this study was to explore kidney failure (KF) in Bardet-Biedl syndrome (BBS), focusing on high-risk gene variants, demographics, and morbidity. We employed...
The aim of this study was to explore kidney failure (KF) in Bardet-Biedl syndrome (BBS), focusing on high-risk gene variants, demographics, and morbidity. We employed the Clinical Registry Investigating BBS (CRIBBS) to identify 44 (7.2%) individuals with KF out of 607 subjects. Molecularly confirmed BBS was identified in 37 KF subjects and 364 CRIBBS registrants. KF was concomitant with recessive causal variants in 12 genes, with BBS10 the most predominant causal gene (26.6%), while disease penetrance was highest in SDCCAG8 (100%). Two truncating variants were present in 67.6% of KF cases. KF incidence was increased in genes not belonging to the BBSome or chaperonin-like genes (p < 0.001), including TTC21B, a new candidate BBS gene. Median age of KF was 12.5 years, with the vast majority of KF occurring by 30 years (86.3%). Females were disproportionately affected (77.3%). Diverse uropathies were identified, but were not more common in the KF group (p = 0.672). Kidney failure was evident in 11 of 15 (73.3%) deaths outside infancy. We conclude that KF poses a significant risk for premature morbidity in BBS. Risk factors for KF include female sex, truncating variants, and genes other than BBSome/chaperonin-like genes highlighting the value of comprehensive genetic investigation.
Topics: Bardet-Biedl Syndrome; Chaperonins; Child; Female; Humans; Male; Mutation; Penetrance; Renal Insufficiency
PubMed: 35112343
DOI: 10.1111/cge.14119