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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 -
Orphanet Journal of Rare Diseases Jul 2023Signs and symptoms of Bardet-Biedl syndrome (BBS) occur during early childhood, progress over time, and place substantial, multifaceted burden on patients and their...
BACKGROUND
Signs and symptoms of Bardet-Biedl syndrome (BBS) occur during early childhood, progress over time, and place substantial, multifaceted burden on patients and their caregivers. Hyperphagia may be a contributing factor to early-onset obesity in BBS; however, there are limited insights into its impacts on patients and caregivers. We quantified disease burden as it relates to the physical and emotional impacts of hyperphagia in BBS.
METHODS
The CAREgiver Burden in BBS (CARE-BBS) study was a multicountry, cross-sectional survey of adult caregivers of patients with BBS who have had hyperphagia and obesity. The survey consisted of questionnaires including Symptoms of Hyperphagia, Impacts of Hyperphagia, Impact of Weight on Quality of Life (IWQOL)-Kids Parent Proxy, and Patient-Reported Outcome Measurement Information System (PROMIS) v1.0-Global Health 7. In addition, clinical characteristics, medical history, and weight management questions were included. Outcomes were scored and summarized descriptively in aggregate and by country, age, and obesity severity according to weight class.
RESULTS
There were 242 caregivers of patients with BBS who completed the survey. Caregivers observed hyperphagic behaviors throughout the day, with negotiating for food (90%) and waking up and asking or looking for food during the night (88%) being the most frequent. Hyperphagia had at least a moderate negative impact on most patients' mood/emotions (56%), sleep (54%), school (57%), leisure (62%), and familial relationships (51%). Hyperphagia affected concentration at school (78%), and symptoms of BBS contributed to patients missing ≥ 1 day of school a week (82%). Responses from the IWQOL-Kids Parent Proxy suggested obesity most greatly negatively affected physical comfort (mean [standard deviation (SD)], 41.7 [17.2]), body esteem (41.0 [17.8]), and social life (41.7 [18.0]). On the PROMIS questionnaire, mean (SD) global health score for pediatric patients with BBS and overweight or obesity (36.8 [10.6]) was lower than the general population (mean, 50).
CONCLUSIONS
Evidence from this study suggests that hyperphagia and obesity may have broad negative impacts on the lives of patients with BBS, including physical health, emotional well-being, school performance, and personal relationships. Therapies that target hyperphagia may alleviate the extensive clinical and nonclinical impacts experienced by patients with BBS and their caregivers.
Topics: Adult; Humans; Child; Child, Preschool; Bardet-Biedl Syndrome; Quality of Life; Cross-Sectional Studies; Obesity; Hyperphagia; Surveys and Questionnaires
PubMed: 37415189
DOI: 10.1186/s13023-023-02723-4 -
EMBO Reports Feb 2021Bardet-Biedl syndrome (BBS) is a genetic disorder caused by the dysfunction of the primary cilium. To date, immunological defects in the disease have not been...
Bardet-Biedl syndrome (BBS) is a genetic disorder caused by the dysfunction of the primary cilium. To date, immunological defects in the disease have not been systematically assessed. In this issue, Tsyklauri and colleagues find, through detailed analysis of BBS mutant animals, that B-cell development is altered in mutant mice (Tsyklauri et al, 2021). The authors further report that BBS patients are more susceptible to autoimmune disorders. This study sheds new light on the potential role of primary cilia in controlling immune function in disease.
Topics: Animals; Autoimmune Diseases; Bardet-Biedl Syndrome; Cilia; Hematopoiesis; Humans; Mice
PubMed: 33511755
DOI: 10.15252/embr.202052180 -
Indian Journal of Nephrology 2022Bardet-Biedl syndrome (BBS) is a rare disorder with a frequency of 1:1,60,000. The disease is inherited in an autosomal recessive manner. Less than 15 cases have been...
Bardet-Biedl syndrome (BBS) is a rare disorder with a frequency of 1:1,60,000. The disease is inherited in an autosomal recessive manner. Less than 15 cases have been reported from India. We present a case of Bardet-Biedl syndrome presenting to the medical emergency with acute breathlessness because of de-compensated renal failure and salient features such as marked polydactyly, central obesity, retinitis pigmentosa, end-stage renal diseases, and mental retardation. Genetic study showed that the patient had BBS genetic variant 9 (MIM#615896), VUS variant. The patient was primarily treated for end-stage chronic renal failure with hemodialysis. We are reporting this case for its rarity and the presence of a novel genetic variant of an unidentified significance as per genome mapping. BBS is often not diagnosed at all or diagnosed late until end-stage renal failure sets in. Timely diagnosis might not help treat the condition but surely improve the quality of life for the patient.
PubMed: 36704599
DOI: 10.4103/ijn.ijn_320_21 -
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 -
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 -
Kidney & Blood Pressure Research 2017Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders. Renal defect, at either structural or functional... (Review)
Review
Bardet Biedl syndrome (BBS) is a rare inherited syndromic condition characterized by renal and extra-renal disorders. Renal defect, at either structural or functional level, is one of the cardinal clinical features, and is a major cause of morbidity. However, the pathogenic mechanism underlying its dysfunction remains largely unknown, and to date only symptomatic treatment with no specific therapy is available for these patients. Elucidating aberrant cellular and/or systemic processes that impact kidney function is therefore a prerequisite to develop targeted innovative therapeutic strategies for the BBS patients. Given the proven role of BBS proteins in the function of the primary cilium (PC) and considering the clinical overlapping of BBS with other ciliopathies, BBS is considered the result of disruption of ciliary activities. The present review aims at giving an updated overview of the spectrum of renal abnormalities in BBS patients according to the existing scientific literature, and discusses the possible role of intrinsic PC dysfunction into the pathogenesis of renal defects based on the most recent findings demonstrating a possible role of systemic factors in favoring the progression of renal disease.
Topics: Bardet-Biedl Syndrome; Cilia; Humans; Renal Insufficiency
PubMed: 29161709
DOI: 10.1159/000484301 -
Orphanet Journal of Rare Diseases Apr 2024Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically...
BACKGROUND
Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype-phenotype correlations.
METHODS
Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype-phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population.
RESULTS
Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad.
CONCLUSIONS
We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.
Topics: Humans; Bardet-Biedl Syndrome; Phenotype; Genotype; Chaperonins; Mutation; Ciliopathies
PubMed: 38584252
DOI: 10.1186/s13023-024-03150-9 -
International Journal of Medical... 2024Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies,...
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.
Topics: Female; Male; Humans; Bardet-Biedl Syndrome; Comorbidity; Heterozygote; Obesity; Renal Insufficiency, Chronic
PubMed: 38617006
DOI: 10.7150/ijms.92766 -
Genes Dec 2022Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) are rare genetic diseases with a number of common clinical features ranging from early-childhood obesity and...
Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) are rare genetic diseases with a number of common clinical features ranging from early-childhood obesity and retinal degeneration. ALMS and BBS belong to the ciliopathies, which are known to have the expression products of genes, encoding them as cilia-localized proteins in multiple target organs. The aim of this study was to perform transcriptomic and proteomic analysis on cellular models of ALMS and BBS syndromes to identify common and distinct pathological mechanisms present in both syndromes. For this purpose, epithelial cells were isolated from the urine of patients and healthy subjects, which were then cultured and reprogrammed into induced pluripotent stem (iPS) cells. The pathways of genes associated with the metabolism of lipids and glycosaminoglycan and the transport of small molecules were found to be concomitantly downregulated in both diseases, while transcripts related to signal transduction, the immune system, cell cycle control and DNA replication and repair were upregulated. Furthermore, protein pathways associated with autophagy, apoptosis, cilium assembly and Gli1 protein were upregulated in both ciliopathies. These results provide new insights into the common and divergent pathogenic pathways between two similar genetic syndromes, particularly in relation to primary cilium function and abnormalities in cell differentiation.
Topics: Child; Humans; Bardet-Biedl Syndrome; Transcriptome; Proteomics; Pediatric Obesity; Alstrom Syndrome; Proteins; Ciliopathies
PubMed: 36553637
DOI: 10.3390/genes13122370