Case Of Bardet-Biedl Syndrome Research Articles

Partial Atrioventricular Septal Defect in a Case of Bardet-Biedl Syndrome: A Rare Association

Bardet-Biedl syndrome (BBS) (MIM 209900) is a genetic disorder with a wide spectrum of clinical manifestations including retinal dystrophy, hypogenitalism, polydactyly, obesity, renal abnormalities and mental retardation. We describe a 13-year-old girl, a known case of Bardet-Biedl syndrome, who was going to undergo hysterectomy due to hydrometrocolpous. She was homozygous autosomal recessive for gene BS57. She was obese and had impaired vision, renal abnormality, borderline intelligence, recurrent urinary tract infection, menstrual problems, normal secondary sex chrematistics and corrected polydactylies. She had also big nose, thin upper lip, slightly everted lower lip, small mouth and retrognathia. Her electrocardiography showed incomplete right bundle branch block. We identified atrioventricular septal defect (AVSD). In conclusion, physicians who deal with cases who suffered from Bardet-Biedl syndrome, should be vigilant about seeking for identification of cardiac anomalies such as partial AVSD. This leads to earlier identification of the existing cardiovascular disease which facilitates appliance of curative measures.

A Case Report of Bardet Biedl Syndrome in a Patient from Pakistan who Presented with Osmotic Symptoms associated with Diabetes Mellitus

Background: The primary features of Bardet Biedl syndrome (BBS) are characterized by retinal degeneration, central obesity, post-axial polydactyly, intellectual impairment, hypogonadism, and renal anomalies. The secondary clinical features are syndactyly, delay in the achievement of developmental milestones, diabetes insipidus, diabetes mellitus, congenital heart disease and liver involvement. It is diagnosed when a patient has either four primary or three primary and two secondary clinical features and the management depends upon those predominant features. Case presentation: A 12-year-old boy presented with polyuria, polydipsia and polyphagia. His developmental milestones were delayed and had syndromic features on physical exmination. Ultrasound of the abdomen and pelvis showed mild right-side hydronephrosis. His BMI was 28 and HbA1c was 18.3%, and values of LH and FSH were decreased. As a result, he was diagnosed with a case of BBS. He was commenced on insulin therapy with Insulin Regular (Human Insulin)and Insulin NPH (Human Insulin). Conclusion: Patients presenting with polyuria, polydipsia, polyphagia along with the presence of syndromic features, should be assessed for BBS as osmotic symptoms associated with diabetes mellitus can be initial clinical presentation of BBS. Its management depends upon the signs and symptoms of the patient. Various options including weight loss, exercise, oral hypoglycemic drugs, and insulin are available to treat diabetes mellitus in BBS. Some cases can have very high levels of HbA1c on initial presentation, which may require insulin without trying oral hypoglycemic drugs to treat diabetes mellitus in BBS.

The Second Case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

Background: Bardet-Biedl syndrome and Laurence-Moon syndrome are rare autosomal recessive disorders with a similar phenotype. They are characterized by the gradual development of phenotype which includes cone-rod retinal dystrophy, obesity, and hypogonadism in males. Other associated abnormalities include learning disability and renal abnormalities. The two conditions are differentiated clinically by the presence of spasticity and the absence of polydactyly in Laurence-Moon syndrome. In 2002, we reported the first patient with Bardet-Biedl syndrome. The boy had polydactyly, obesity, retinal degeneration, and was hospitalized at the University Hospital in Al-Kadhimiyia because of the development of chronic renal failure. Patients and methods: The case of a 9-year-old obese Kurdish girl who had polydactyly of the hands and feet associated with reduced visual acuity is described.Results: A 9-year-old obese Kurdish girl had polydactyly of the hand and feet associated with reduced visual acuity that was attributed to myopia which was partially corrected with eye glasses. The parents were unrelated, and her younger 5-year sister had polydactyly of the feet only. No other family member known to have polydactyly. Both sisters had their extra-digits removed surgically. The girl was studying at fourth grade primary school and the parents reported no learning disability. Fundoscopy showed normal optic disc and periphery of the retina. The presence of retinitis pigmentosa was excluded. However, the foveal reflex was reported to be abnormal by the oophthalmologist. Electroretinography showed evidence of cone-rod dystrophy.Conclusion: The second case of Bardet-Biedl syndrome from Iraq is reported. The current evidence-based expert opinion suggests the use of long tem supplementation of citicoline, co-enzyme Q10 and lutein with hope of retarding the progression to blindness.

The second case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

Background: Bardet-Biedl syndrome and Laurence-Moon syndrome are rare autosomal recessive disorders with a similar phenotype. They are characterized by the gradual development of phenotype which includes cone-rod retinal dystrophy, obesity, and hypogonadism in males. Other associated abnormalities include learning disability and renal abnormalities. The two conditions are differentiated clinically by the presence of spasticity and the absence of polydactyly in Laurence-Moon syndrome. In 2002, we reported the first patient with Bardet-Biedl syndrome. The boy had polydactyly, obesity, retinal degeneration, and was hospitalized at the University Hospital in Al-Kadhimiyia because of the development of chronic renal failure. Patients and methods: The case of a 9-year-old obese Kurdish girl who had polydactyly of the hands and feet associated with reduced visual acuity is described. Results: A 9-year-old obese Kurdish girl had polydactyly of the hand and feet associated with reduced visual acuity that was attributed to myopia which was partially corrected with eye glasses. The parents were unrelated, and her younger 5-year sister had polydactyly of the feet only. No other family member known to have polydactyly. Both sisters had their extra-digits removed surgically. The girl was studying at fourth grade primary school and the parents reported no learning disability. Fundoscopy showed normal optic disc and periphery of the retina. The presence of retinitis pigmentosa was excluded. However, the foveal reflex was reported to be abnormal by the oophthalmologist. Electroretinography showed evidence of cone-rod dystrophy. Conclusion: The second case of Bardet-Biedl syndrome from Iraq is reported. The current evidence-based expert opinion suggests the use of long tem supplementation of citicoline, co-enzyme Q10 and lutein with hope of retarding the progression to blindness.

The second case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

The second case of Bardet-Biedl syndrome from Iraq: An educational article and expert opinion

Bardet–Biedl syndrome: Case report from a tertiary-care hospital in Srinagar, India

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathic disorder affecting multiple organ systems. The main clinical features are marked central obesity, retinal dystrophy, polydactyly, mental retardation, hypogonadism, and renal dysfunction. It affects both males and females. Herein, we report an interesting case of BBS with features of the BBS yet without cone-rod dystrophy, which is considered one of the hallmark features of this condition. To the best of our knowledge, this is the first report of Bardet–Biedl syndrome with the absence of cone-rod dystrophy and a normal fundus examination on the Indian subcontinent. Key words: Bardet–Biedl syndrome; Ciliopathic disorder; Polydactyly

Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome

Bardet–Biedl syndrome (BBS) is an autosomal recessive ciliopathy characterized by extensive inter- and intra-familial variability, in which oligogenic interactions have been also reported. Our main goal is to elucidate the role of mutational load in the clinical variability of BBS. A cohort of 99 patients from 77 different families with biallelic pathogenic variants in a BBS-associated gene was retrospectively recruited. Human Phenotype Ontology terms were used in the annotation of clinical symptoms. The mutational load in 39 BBS-related genes was studied in index cases using different molecular and next-generation sequencing (NGS) approaches. Candidate allele combinations were analysed using the in silico tools ORVAL and DiGePred. After clinical annotation, 76 out of the 99 cases a priori fulfilled established criteria for diagnosis of BBS or BBS-like. BBS1 alleles, found in 42% of families, were the most represented in our cohort. An increased mutational load was excluded in 41% of the index cases (22/54). Oligogenic inheritance was suspected in 52% of the screened families (23/45), being 40 tested by means of NGS data and 5 only by traditional methods. Together, ORVAL and DiGePred platforms predicted an oligogenic effect in 44% of the triallelic families (10/23). Intrafamilial variable severity could be clinically confirmed in six of the families. Our findings show that the presence of more than two alleles in BBS-associated genes correlated in six families with a more severe phenotype and associated with specific findings, highlighting the role of the mutational load in the management of BBS cases.

Bardet Biedl Syndrome-Report of three Cases and Review of Recent Articles

Purpose: To report three cases of a rare inherited familial disorder of Bardet-Biedl Syndrome (BBS). Study Design: Observational case report. Method: Two out of eight siblings presented in their second decade of life with dimness of vision in both eyes since birth. The third one is the only person of the family presented also in second decade of life with gradual blurring of vision in both eyes and outward deviation of left eye. Detail clinical history was taken. Physical, anthropometric, ophthalmic, psychological examination was done and appropriate clinical investigations were performed to exclude other systemic disorder. Review of recent literatures was done. Result: First two cases were brothers, who were mentally retarded child with delayed developmental mile stone. They were short, obese and had polydactyly, gynecomastia, hypogonadism. Their vision was poor and had retinitis pigmentosa with optic atrophy. The third one was also mentally retarded and had polydactyly, trunkal obesity, atypical retinitis pigmantosa with optic atrophy. They did not had deafness or any systemic abnormalities. Depending on clinical findings they were diagnosed as a case of BBS.

A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.

Cilia and flagella are formed around an evolutionary conserved microtubule-based axoneme and are required for fluid and mucus clearance, tissue homeostasis, cell differentiation and movement. The formation and maintenance of cilia and flagella require bidirectional transit of proteins along the axonemal microtubules, a process called intraflagellar transport (IFT). In humans, IFT defects contribute to a large group of systemic diseases, called ciliopathies, which often display overlapping phenotypes. By performing exome sequencing of a cohort of 167 non-syndromic infertile men displaying multiple morphological abnormalities of the sperm flagellum (MMAF) we identified two unrelated patients carrying a homozygous missense variant adjacent to a splice donor consensus site of IFT74 (c.256G > A;p.Gly86Ser). IFT74 encodes for a core component of the IFT machinery that is essential for the anterograde transport of tubulin. We demonstrate that this missense variant affects IFT74 mRNA splicing and induces the production of at least two distinct mutant proteins with abnormal subcellular localization along the sperm flagellum. Importantly, while IFT74 deficiency was previously implicated in two cases of Bardet-Biedl syndrome, a pleiotropic ciliopathy with variable expressivity, our data indicate that this missense mutation only results in primary male infertility due to MMAF, with no other clinical features. Taken together, our data indicate that the nature of the mutation adds a level of complexity to the clinical manifestations of ciliary dysfunction, thus contributing to the expanding phenotypical spectrum of ciliopathies.

A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.

P05.03: Antenatal sonographic and genetic diagnosis of two cases of Bardet‐Biedl syndrome

Bardet-Biedl syndrome (BBS) belongs to the group of ciliopathies and has an autosomal-recessive inheritance with 22 genes known already. In the child it is associated with retinal dystrophy, obesity, neurological and psychic disabilities, hypogonadism, postaxial polydactyly and renal dysfunction. There are overlapping with other ciliopathies. Prenatal report of BBS is rather scarce. We report the features of two prenatally confirmed cases of BBS. Case 1: On screening US at 22 weeks (G2-P1) in a non-consanguineous patient enlarged, fetal hyperechogenic kidneys were detected. The detailed examination showed a hexadactyly at one foot, with no other malformations. A BBS was suspected and amniocentesis revealed a homozygotic mutation in the BBS1 gene. Both parents were found to be heterozygote carriers. The parents opted for pregnancy termination. Case 2: In the primigravida non-consanguineous 30y old patient first trimester screening revealed a polydactyly of both hands and feet with no additional anomalies. CVS showed a male karyotype. A follow up at 18 weeks showed in addition large hyperechogenic kidneys with no other signs of a ciliopathy. Bardet-Biedl syndrome was suspected and a deletion of exons 14-17 of the BBS-1 was found. Both parents were found to be heterozygote carriers. Patient opted for pregnancy termination. Prenatal diagnosis of BBS remains difficult but these two cases show that the presence of hyperechogenic kidneys and polydactyly only should prompt the careful targeted examination for a BBS. The additional presence of intracerebral, skeletal or other malformations can be the hint for other ciliopathies, including Joubert or Meckel syndrome. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Bardet Biedl syndrome - report of a very rare case

AbstractBardet Biedl Syndrome is a autosomal recessive condition with a wide spectrum of clinical features. The principal manifestations of the syndrome are Post axial polydactyly, Retinitis Pigmentosa, truncal obesity, hypogonadism & renal dysfunction. The authors report a case of Bardet Biedl Syndrome in a young girl diagnosed on the basis of post axial polydactyly, retinitis pigmentosa and other systemic features. Postaxial polydactyly is one of the earliest and most common manifestation of Bardet Biedl syndrome, followed by truncal obesity and retinitis pigmentosa. Renal failure is the major cause of morbidity and mortality. The importance of polydactyly lies in the fact that, such finding can be helpful in antenatal diagnosis to see its inheritance, counseling of such families and at times may be treated by surgical correction.

Genetics of human Bardet-Biedl syndrome, an updates.

Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystemic human genetic disorder characterized by six major defects including obesity, mental retardation, renal anomalies, polydactyly, retinal degeneration and hypogenitalism. In several cases of BBS, few other features such as metabolic defects, cardiovascular anomalies, speech deficits, hearing loss, hypertension, hepatic defects and high incidence of diabetes mellitus have been reported as well. The BBS displays extensive genetic heterogeneity. To date, 19 genes have been mapped on different chromosomes causing BBS phenotypes having varied mutational load of each BBS gene. In this review, we have discussed clinical spectrum and genetics of BBS. This report presents a concise overview of the current knowledge on clinical data and its molecular genetics progress upto date.

Bardet Biedl syndrome – report of a very rare case

Bardet Biedl Syndrome is a autosomal recessive condition with a wide spectrum of clinical features. The principal manifestations of the syndrome are Post axial Polydactyly, Retinitis Pigmentosa, truncal obesity, hypogonadism & renal dysfunction. The authors report a case of Bardet Biedl Syndrome in a young girl diagnosed on the basis of post axial Polydactyly, retinitis pigmentosa and other systemic features. Postaxial Polydactyly is one of the earliest and most common manifestation of Bardet Biedl syndrome, followed by truncal obesity and retinitis pigmentosa. Renal failure is the major cause of morbidity and mortality. The importance of Polydactyly lies in the fact that, such finding can be helpful in antenatal diagnosis to see its inheritance, counseling of such families and at times may be treated by surgical correction.

A Rare Classical Presentation of Bardet-Biedl Syndrome in a Three-Year-Old Male from South East Nigeria: A Case Report

Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by obesity, post-axial polydactyly, renal abnormalities, mental retardation, pigmentary retinopathy and hypogenitalism. Diagnosis is rare in early childhood, and only few of the features are present at that age. This is because the disease is slow evolving. However, it is possible to find majority of the component of this syndrome in very young children. A 3-year old very obese male presented with clinical features of sepsis and congestive cardiac failure. He is a product of non-consanguineous marriage with unremarkable family history. Both parents are of the Ibo tribe in Nigeria. Polydactyly was noticed at birth. There was delay in some aspects of his developmental milestone. Examination revealed mild hypertelorism and retrognathia, polydactyly of both feet with syndactyly of the big and second toes. Other findings were short broad hands, mottled pigments on the retina, moderate mental retardation, hypogenitalism, nephrotic syndrome, renal tubulopathy, hyperglycaemia and hypopigmented skin lesions. A case of BBS with all the primary features and some secondary manifestations in a very young child is hereby reported. A high index of suspicion for BBS should be shown in any young child with at least one of the features of this syndrome. This will enhance earlier diagnosis and improve disease outcome.

IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease.

Rare cause of pediatric obesity: Bardet - Biedl Syndrome

Bardet - Biedl syndrome (BBS) is a rare autosomal recessive disorder, characterized by central obesity, retinal pigmentation, polydactyly, mental retardation, hypogonadism, and renal dysfunction. Other features may include deafness, diabetes mellitus, genitourinary abnormalities, short stature, hormonal abnormalities, developmental defects, and speech problems. We report a case of BBS who presented with night blindness, marked central obesity, polydactyly, syndactyly, hypogonadism, micropenis, and behavioral problems, along with a brief review of the literature.

The Genetic Determination of Tendency to Cardiovascular Disease in the Two Bardet Biedl Syndrome Cases

The Genetic Determination of Tendency to Cardiovascular Disease in the Two Bardet Biedl Syndrome Cases

A Case of Bardet-Biedl Syndrome with a Pituitary Tumor and Growth Hormone Deficiency

A Case of Bardet-Biedl Syndrome with a Pituitary Tumor and Growth Hormone Deficiency

Bardet–Biedl Syndrome: A Rare Cause of Chronic Kidney Disease

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive condition characterized by retinitis pigmentosa, postaxial polydactyly, central obesity, and renal involvement. Renal failure is the commonest cause of death. We report a case of BBS with chronic kidney disease (CKD) at younger age (17year) from India.This diagnosis should be considered in patients with renal disease and the characteristic phenotype of retinitis pigmentosa, postaxial polydactyly and central obesity. These patients should undergo regular monitoring of renal function test to early diagnosis and treatment of CKD to prevent morbidity and mortality. Renal transplantation is a viable option of renal replacement therapy in these patients. These findings are valuable for comparing phenotype of BBS patients with CKD from various national and international centers.