|Year : 2023 | Volume
| Issue : 6 | Page : 520-522
Bardet–Biedl syndrome with choledochal cyst: Rare association with a novel variant
Saket Kumar1, AG Harisankar1, Nidhi Singh2, Singh Rakesh Kumar1, Nilay Mayank3
1 Department of Surgical Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
2 Department of Anesthesiology, BIG Apollo Spectra Hospitals, Agamkuan, Patna, Bihar, India
3 Department of Medical Genetics, Post Graduate Institute of Child Health, Noida, Uttar Pradesh, India
|Date of Submission||31-May-2023|
|Date of Acceptance||25-Jun-2023|
|Date of Web Publication||02-Nov-2023|
Department of Surgical Gastroenterology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna - 800 014, Bihar
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Bardet–Biedl syndrome is an autosomal-recessive ciliopathic disorder affecting multiple organ systems. Characteristic features include progressive retinal dystrophy, obesity, polydactyly hypogonadism, mental retardation, and renal disorders. Other manifestations include congenital heart diseases, hepatic fibrosis, ataxia, and diabetes. Approximately 30% of patients with Biedl–Bardet syndrome (BBS) have hepatobiliary disorders such as periportal fibrosis, nonalcoholic fatty liver disease, and cystic dilation of the bile ducts. The association of BBS with choledochal cysts (CDC) is extremely rare. Here, we report a case of a 14-year-old boy with a novel variant of BBS and associated type IV CDC. The patient was managed surgically with CDC excision and Roux-en-Y hepaticojejunostomy.
Keywords: Bardet–Biedl syndrome, biliary cyst, choledochal cyst, ciliopathy, congenital anomaly, genetic mutation
|How to cite this article:|
Kumar S, Harisankar A G, Singh N, Kumar SR, Mayank N. Bardet–Biedl syndrome with choledochal cyst: Rare association with a novel variant. J Indian Assoc Pediatr Surg 2023;28:520-2
|How to cite this URL:|
Kumar S, Harisankar A G, Singh N, Kumar SR, Mayank N. Bardet–Biedl syndrome with choledochal cyst: Rare association with a novel variant. J Indian Assoc Pediatr Surg [serial online] 2023 [cited 2023 Nov 28];28:520-2. Available from: https://www.jiaps.com/text.asp?2023/28/6/520/389315
| Introduction|| |
Biedl–Bardet syndrome (BBS) is a rare autosomal recessive ciliopathic disorder associated with multisystem involvement. It results due to biallelic loss of function pathogenic in at least 26 genes identified to date. The diagnosis of this syndrome is based on the clinical criteria suggested by Forsythe and Beales.
Choledochal cyst (CDC) is another rare congenital anomaly characterized by dilatation of intra-and/or extrahepatic bile duct. The Asian population, particularly those of Japanese and Korean descent, exhibits the highest incidence of CDCs compared to other ethnic groups. More than 60%–80% of cases of CDC are diagnosed during childhood. Based on morphology and intra-or extrahepatic involvement, CDC has been classified into five types by Todani et al. Association of CDC with BBS is extremely rare and very few cases have been reported in the medical literature. Whether this association is coincidental or a rare phenotypic expression of BBS is a subject for further research.
| Case Report|| |
A 14-year-old Indian boy from nonconsanguineous family presented with jaundice and recurrent upper abdominal pain for 3 months. He also had gradually decreasing visual perception and tunnel vision for the last 6 months. His parents had noted hyperphagia and progressive weight gain for the last 3 years. On detailed clinical examination, he had mild retrognathia, high arched palate, polydactyly of all four limbs, bilateral gynecomastia, micropenis, and small testes [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. His body mass index was 31 kg/m2. Fundoscopy revealed retinitis pigmentosa [Figure 2]b. Based on Forsythe and Beales criteria2, a diagnosis of BBS was made. With parents' consent, the blood sample was obtained from the boy for genetics analysis. Exome sequencing led to the identification of a heterozygous pathogenic variant in exon 2 of the BBS10 gene. Another novel variant of uncertain clinical significance (The American College of Medical Genetics and Genomics (ACMG) 2015 criteria) was also detected in exon 2 of the BBS10 gene [Figure 2]c and [Figure 2]d. Genetic testing of either of the parents could not done be to financial reasons.
|Figure 1: (a) Patient with Bardet–Biedl phenotype. Central obesity, gynecomastia, and hypogonadism are evident in the picture; (b and c) polydactyly in both hands and feet; (d) the external genitalia of patient feature micropenis and microorchidism|
Click here to view
|Figure 2: (a) Magnetic resonance cholangiopancreaticography image showing dilation of intra- and extra-hepatic bile ducts (arrow), suggestive of Todani type IVA choledochal cyst; (b) fundoscopy showing retinitis pigmentosa; (c and d) Integrative genomic viewer pictures showing genetic variants detected on the BBS10 gene|
Click here to view
The patient was further evaluated with magnetic resonance cholangiopancreaticography (MRCP) for his abdominal complaints, which revealed Todani type IVA CDC [Figure 2]a. After proper preparation, he underwent CDC excision with Roux-en-Y hepaticojejunostomy. Postoperative recovery was uneventful and the patient remains symptom-free in the follow-up.
| Discussion|| |
BBS is a rare ciliopathic autosomal recessive genetic disease. To date, a total of 26 distinct genes have been found to be associated with BBS., Mutations in BBS1 to BBS18 account for about 70%–80% of cases worldwide. In Indian population, BBS1 and BBS10 mutations account for only 7% and 10% of diagnoses, respectively, while BBS3 (14%), BBS9 (10%), and BBS6 (10%) mutations are more frequent. In our patient, we identified a known pathogenic variant associated with this syndrome, specifically the c. 271dupT mutation. In addition, we discovered a novel mutation, c.1845_1861del, which has been identified for the first time in our patient.
Diagnostic criteria for Biedl–Bardt syndrome were described by Beales et al. He suggested four primary features or three primaries with two secondary features for the diagnosis of this syndrome. Primary features include retinitis pigmentosa, polydactyly, obesity, genital anomalies, renal anomalies, and learning difficulty. Secondary features include speech delay, developmental delay, diabetes mellitus, dental anomalies, congenital heart disease, brachydactyly/syndactyly, ataxia, and anosmia. Our patient had all four primary features of BBS.
Moreover, our patient had pain abdomen and jaundice due to underlying CDC. Among the various theories proposed for the pathogenesis of CDC, Babbitt's theory is widely regarded as the most accepted explanation. According to this theory, the presence of an anomalous pancreaticobiliary bile duct junction leads to the development of a long common channel (>15 mm). This anatomical abnormality predisposes individuals to increased biliary pressure and reflux of pancreatic secretion into the bile ducts, contributing to the formation of CDCs.
MRCP is currently the most accurate preoperative imaging study to assess cyst anatomy and classify the disease according to standard Todani classification., Based on MRCP findings, our patient was diagnosed to have type IVA CDC. The excision of extrahepatic bile ducts with Roux-en-Y hepaticojejunostomy reconstruction was performed.
CDC in a BBS patient is of rare occurrence. The management of BBS involves a multidisciplinary, personalized approach to address organ dysfunction. In cases where surgical intervention is necessary for a patient with BBS, it is crucial to conduct a thorough evaluation and optimization to ensure a safe outcome. This involves assessing the patient for any subclinical cardiac, renal, respiratory, or neurological disorders to minimize the risks associated with surgery. Precautionary measures, such as the recommendation of incentive spirometry and chest physiotherapy, are advised during the perioperative period to optimize respiratory function. In addition, medications known to have potential cardiac and renal toxicity are avoided.
To conclude, CDC should be considered in the differential diagnosis of patients with BBS presenting with biliary symptoms. Preoperative evaluation and optimization are mandatory for safe surgical outcomes.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: Results of a population survey. J Med Genet 1999;36:437-46.
Forsyth R, Gunay-Aygun M. Bardet-Biedl Syndrome Overview. 2003 Jul 14 [updated 2023 Mar 23]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.
Baison GN, Bonds MM, Helton WS, Kozarek RA. Choledochal cysts: Similarities and differences between Asian and Western countries. World J Gastroenterol 2019;25:3334-43.
Forsyth R, Gunay-Aygun M. Bardet-Biedl Syndrome Overview. 2003 Jul 14 [updated 2023 Mar 23]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 20301537.
Warid MM, Dutta A, Uddin MS, Elahi MN, Das BC, Bardet Biedl syndrome with choledochal cyst; A very rare case report. J Med Sci Res 2019;31:40-3.
M'hamdi O, Ouertani I, Chaabouni-Bouhamed H. Update on the genetics of Bardet-Biedl syndrome. Mol Syndromol 2014;5:51-6.
Sathya Priya C, Sen P, Umashankar V, Gupta N, Kabra M, Kumaramanickavel G, et al
. Mutation spectrum in BBS genes guided by homozygosity mapping in an Indian cohort. Clin Genet 2015;87:161-6.
Babbitt DP. Congenital choledochal cysts: New etiological concept based on anomalous relationships of the common bile duct and pancreatic bulb. Ann Radiol (Paris) 1969;12:231-40.
[Figure 1], [Figure 2]