|Year : 2020 | Volume
| Issue : 2 | Page : 81-84
Rare presentation of bardet–biedl syndrome as chronic liver disease with splenomegaly
J Manjula, K Ravi, VN Prashanth
Department of General Medicine, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India
|Date of Submission||03-Sep-2019|
|Date of Acceptance||05-Jan-2020|
|Date of Web Publication||18-Apr-2020|
Dr. J Manjula
Department of General Medicine, Victoria Hospital, Bangalore Medical College and Research Institute, K R Market, Bengaluru - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
Bardet–Biedl syndrome is a rare ciliopathic human autosomal-recessive disorder. It is a disorder that affects many parts of the body. Less than 15 cases have been reported from India. The signs and symptoms of this condition vary among affected individuals, even among members of the same family. It is characterized principally by the cardinal symptoms of marked central obesity, retinal dystrophy, polydactyly, mental retardation, hypogonadism, and renal dysfunction. The frequency of the syndrome is estimated to be 1:160,000.
Keywords: Bardet–Biedl syndrome, chronic liver disease, developmental delay, polydactyly, retinitis pigmentosa
|How to cite this article:|
Manjula J, Ravi K, Prashanth V N. Rare presentation of bardet–biedl syndrome as chronic liver disease with splenomegaly. APIK J Int Med 2020;8:81-4
|How to cite this URL:|
Manjula J, Ravi K, Prashanth V N. Rare presentation of bardet–biedl syndrome as chronic liver disease with splenomegaly. APIK J Int Med [serial online] 2020 [cited 2020 Jul 11];8:81-4. Available from: http://www.ajim.in/text.asp?2020/8/2/81/282845
| Introduction|| |
The Bardt Biedel syndrome is a rare ciliopathic human autosomal recessive disorder. Less than 15 cases have been reported from India. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.
It is characterized principally by cardinal symptoms of marked central obesity, retinal dystrophy, polydactyly, mental retardation and hypogonadism and renal dysfunction. The frequency of the syndrome is estimated to be 1:1,60000.
The Bardet–Biedl syndrome is an autosomal recessive disorder with a wide range of clinical features. The primary clinical features include rod-cone dystrophy, postaxial polydactyly, central obesity, cognitive impairment, male hypogonadism, complex female genitourinary malformations and renal dysfunction. The secondary features include speech disorders or delays, eye abnormalities like strabismus, cataract and astigmatism, brachydactyly or syndactyly, developmental delays, ataxia, Diabetes Mellitus, craniofacial dysmorphism, nephrogenic diabetes insipidus, hepatic fibrosis and congenital heart disease.
Beales et al., have suggested that the presence of four primary or three primary plus two secondary features is diagnostic. The rare associations include hypothyroidism, Hirschsprung's disease, epilepsy, genital anomalies, anal stenosis and an abnormal dentition.
| Case Report|| |
This is a case which is not often reported but probably seen. A 22-year-old male patient born out of non-consanguineous marriage reported to the medicine outpatient department with complaint of easy fatigability. His background problems included behavioral issues, subnormal mentality, poor scholastic performance and night blindness, and upper limb polydactyly [Figure 1] and [Figure 2].
|Figure 2: General physical examination of patient with Bardet–Biedl syndrome|
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On examination, developmental age was lagging behind the chronological age. He underwent detailed neuropsychiatric assessment and was diagnosed with cognitive deficit disorder with dyslexia and dyscalculia. His height is 132 cm and weight is 55kg with BMI of 31.56kg/m2. General physical examination revealed low-set ears, high-arched palate, upper limb polydactyly with genu valgum of both lower limb, pallor, and icterus. Pulse rate and blood pressure were 78 bpm and 112/70 mmHg, respectively.
On per-abdomen examination, massive spleen was palpable, firm in consistency. However, liver was not palpable. The patient underwent detailed workup for anemia, chronic disease, and splenomegaly. Severe iron deficiency anemia secondary to upper gastrointestinal (GI) blood loss with deranged liver function test was present. The patient had hyperbilirubinemia and hypoalbuminemia with altered enzyme levels. He underwent contrast-enhanced computed tomography to identify the causes for diffuse liver disease that showed “features suggestive of chronic parenchymal liver disease, splenomegaly with dilated splenic artery and vein; multiple collaterals in the lesser curvature and peritoneum with mild ascites; and mesenteric and retroperitoneal lymphadenopathy with cardiomegaly and bilateral pleural effusion” [Figure 3]. In view of chronic liver disease (CLD), the patient underwent upper GI endoscopy that showed esophageal varices and portal hypertensive gastropathy. Extensive workup for CLD was done – Wilson's disease was ruled out by 24-h urine copper, serum ceruloplasmin levels, and slit-lamp examination for Kayser–Fleischer ring; serum iron profile showed severe iron deficiency anemia and thus hemochromatosis was ruled out. ANA profile and autoimmune hepatitis workup are normal. Patient's attenders did not give consent for liver biopsy. Electrocardiogram was normal; however, two-dimensional echocardiogram showed dilated left atrium and left ventricle (LV) with mild tricuspid regurgitation and pulmonary arterial hypertension, pulmonary artery systolic pressure 44 mmHg with normal systolic function, Grade II LV diastolic dysfunction, and LV ejection fraction = 61%. The patient underwent magnetic resonance imaging that showed T1 and FLAIR hyperintensity in bilateral globus pallidus and substantia nigra – likely suggestive of hepatic encephalopathy and nonparenchymal atrophy disproportionate for age [Figure 4].
|Figure 3: Contrast-enhanced computed tomography abdomen showing liver cirrhosis with splenomegaly|
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|Figure 4: Magnetic resonance imaging brain – T1 hyperintensity in bilateral globus pallidus and substantia nigra|
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Ophthalmologic examination showed visual acuity of 6/12 and 6/36 in the right and left eye, respectively. Fundus examination showed pallor of the optic disc and bilaterally attenuated blood vessels and retinal epithelium dystrophy, retinal pigment changes of retinitis pigmentosa with mild night blindness, and constricted visual field.
Apart from deranged liver function test, other investigations such as complete hemogram, renal function test, and urine analysis and microscopic analysis were normal.
Patient's parents were counseled and called for regular follow-up to observe for progression of renal disease, for behavioral therapy, and for evaluation of CLD. The patient was also advised regarding allogeneic liver transplantation as per gastroenterologist consultation.
| Discussion|| |
Bardet–Biedl syndrome (BBS) was named after Georges Bardet and Arthur Biedl. The patient discussed above is a classic case of BBS. This syndrome was described by Bardet and Biedl in 1920. It was later erroneously coupled with another disorder described by Laurence and Moon and was consequently referred to Laurence–Moon–Biedl syndrome. BBS is distinguished from the much rarer Laurence–Moon syndrome, in which retinal pigmentary degeneration, mental retardation, and hypogonadism occur in conjunction with progressive spastic paraparesis and distal muscle weakness but without polydactyly. In 1999, modified diagnostic criteria were defined after a study conducted in England in 109 BBS patients. Patients who had four primary characteristics or three primary and second secondary criteria were identified as BBS [Table 1]. Our case had four primary and three secondary diagnostic criteria. However, the patient had features suggestive of CLD which is not a common manifestation of BBS. Various forms of hepatic involvement are described in the literature. Hepatic involvement may occur as perilobular fibrosis, periportal fibrosis with small bile ducts, bile duct proliferation with cystic dilatation, biliary cirrhosis, portal hypertension, and congenital cystic dilations of both the intrahepatic and extrahepatic biliary.
|Table 1: Modified diagnostic criteria and clinical manifestation in Bardt- Biedl syndrome|
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The syndrome is transmitted as an autosomal-recessive trait. Recent advances in genetics have enabled investigators to define syndromes by specific mutations. Eleven genes are known to be associated with this syndrome: BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, MKKS/BBS6, BBS7, TTC8/BBS8, B1/BBS9, BBS10, and TRIM32/BBS11.
BBS has an adverse prognosis, and treatment depends on clinical features and organs involved. Their survival and quality of life depend on the severity of clinical features, as well as on the quality of the medical care they receive.
| Conclusion|| |
This case is a typical case of BBS, which is not often reported but probably seen. Informed written consent for publication was taken. This case of BBS has four cardinal features such as retinitis pigmentosa, postaxial polydactyly, central obesity, mental retardation with four secondary features such as speech disorder, dental crowding + high arched palate, learning disability, and hepatic fibrosis. In addition to the common presentation of BBS, our case had a rare presentation of CLD, of unknown etiology presenting as anemia.
The condition is supposed to be rare, but this may be due to failure to diagnose incomplete or partial cases, hence less often reported. Physicians, pediatricians, and ophthalmologists should be aware of this syndrome because of two reasons. First, the syndrome has got grave prognosis and second, patient seek the first consultation in these specialties, by whom they should be guided to appropriate superspecialties.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]