3. Discussion and Conclusion:
Bardet-Biedl syndrome (BBS) is a rare genetic disorder, which has an autosomal recessive pattern of inheritance. It has an estimated incidence of 1 in 150 000–160 000 in North American and European populations, but the incidence appears to be higher in areas with high levels of consanguinity [4]
Primary cilia play an important role in sensory perception and various signalling pathways; any defect in cilia can lead to disorders called ciliopathies. BBS falls under the spectrum of these disorders. Where the function of various ciliated systemic organs is disturbed, which results in systemic manifestations. The spectrum of BBS mutation varies; to manifest the disease some patients require three mutations. This genetic heterogeneity has made genetic analysis expensive and time-consuming as a result it was restricted to difficult cases and research studies. The diagnosis of BBS can be concluded by clinical criteria alone. Yet the underlying mechanisms that cause the disease are still not fully understood.
BBS is heterogeneous genetically, with 21 BBS genes (BBS1–BBS21) identified; the two main genes involved in BBS are BBS1 and BBS10, which are present in more than 20% of the cases. [5] Patients with mutations in BBS1  generally present later than patients with mutations in BBS10 , due to a milder phenotype and a later onset of retinal degeneration. BBS proteins localize to the centrosome and regulate the biogenesis and functions of the cilia.
The primary clinical features of BBS include rod-cone dystrophy, postaxial polydactyly, central obesity, cognitive impairment, male hypogonadism, complex genital anomalies and renal dysfunction [6 ]. 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 left ventricular hypertrophy/congenital heart disease. [7] The presence of four primary features or three primary and two secondary features are required to diagnose BBS.
A wide range of renal abnormalities has been reported, including chronic renal failure, parenchymal cysts, calyceal clubbing, fetallobulation, renal scarring, unilateral agenesis, dysplastic kidneys, renal calculi and vesicoureteric reflux. The natural history of renal disease in BBS is still questionable. Renal impairment can be due to either primary causes(e.g., cystic renal disease) or secondary to hypertension, diabetes or metabolic syndrome. The most common cause of mortality among BBS patients is renal failure, as 25% of the patients die from it by the age of 44 [8]. Diabetes mellitus and hypertension are frequently observed in BBS patients than the general population, which can affect the progression of renal failure. The management of renal failure due to BBS is similar to any other cause. All three modalities of renal replacement therapy, i.e. chronic peritoneal dialysis, haemodialysis and renal transplantation can be applied in these patients. [9]
Hepatic involvement among BBS patients include peri-lobular fibrosis, periportal fibrosis, biliary cirrhosis, and bile duct proliferation with cystic dilatation to portal hypertension [10]. Hepatic haemangioma and gallbladder stones, as in our patient, are very rarely reported in the literature. Shrinkhalet al reported a case of BBS with hepatomegaly, where ultrasonography showed a hepatic haemangioma. [11] Gallbladder stones can be sought to be due to obesity.
Early diagnosis is important to guide the patient follow-up through regular assessment of renal function, blood glucose, weight, blood pressure, ophthalmic exams and imaging studies. To date, there is no curative treatment for BBS. Management of BBS requires a multidisciplinary approach team of paediatricians, nephrologists, orthopaedic surgeons, cardiologists, ophthalmologists, dental specialists, speech pathologist, and audiologists. Nephrotoxic drugs should be avoided, in addition toLifestyle modifications, which can help in reducing the BMI and preventingthe harmful consequences of obesity. TheUse of visual aids can improve patients’ performance in their daily activities.Where as, for the cosmetic purposes, surgical removal of accessory digits can be applied. Learning disabilities may necessitate entrance to special schools and educational programs. Finally, genetic counselling can be of great benefit for affected individuals and their families.
In conclusion, BBS is a rare clinical syndrome, which may be passed undiagnosed by many clinicians. Renal impairment is one of the leading causes of death in the syndrome, so early detection of BBS is vital. The presence of postaxial polydactyly, blindness or learning disabilities in addition to renal malformations or high renal profile should ring a bell about the possibility of BBS. Hepatic haemangioma and gallstones were rarely reported clinical features in BBS. The addition of these features to the secondary diagnostic features of BBS should be considered.