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.