Bardet-Biedl syndrome

The Bardet-Biedl syndrome is a rare genetically heterogeneous, autosomal recessive inherited disorder with wide variability in expression. It presents with varied clinical manifestations like retinitis pigmentosa, polydactyly, central obesity, mental retardation and renal dysfunction. Other rare manifestations include diabetes mellitus, heart disease, hepatic fibrosis and neurological manifestations. Mutations in 16 genes have been identified as causative factors. We, here, have presented a 12 year old male patient exhibiting characteristic features of Bardet Biedl syndrome.


Introduction
Genetic disorders are common causes of morbidity and mortality in infants and children.Among these genetic disorders, Bardet-Biedl syndrome is a rare disorder.The prevalence rates of 1:140000 to 1:1,60,000 are in North America and Europe respectively. 1The incidence is much higher in some populations with a high level of consanguinity or those that are geographically isolated, with disease incidence of 1 in 13,000 in the isolated populations of Newfoundland and 1 in 17,000 live births in Kuwait.Male to female ratio is approximately 1.3:1. 2,36][7][8][9][10][11]

Case Report
A 12 year old boy, 3 rd issue of non-consanguinous parents, admitted on July 2015 in the Pediatric ward of Bangabandhu Sheikh Mujib Medical University with the complaints of obesity, poor genital development in relation to other peers, poor vision.On query, mother also gave history of poor interest to surroundings and difficulty with learning.
There was no history of urinary problem, palpitations, hearing impairment, breathing difficulty, dental problem, and limb weakness.He was delivered at home by normal vaginal delivery at term.Birth history was not significant except for the anomaly of polydactyly in his four limbs.He had delayed developmental milestones along with speech delay.
On examination, he had moon face, alopecia and dull looking appearance (Figure 1).His weight was 54 kg (on 95th centile).Height was 142 cm (in between 10-25th centile).Body mass index was 26.8 kg/m 2 (on 97th centile).Bed side urine for albumin and sugar was negative.Musculoskeletal system examination revealed polydactyly in all limbs, short, broad, stubby fingers and toes (Figure 2).He had high arch palate with abdominal distension and hepatomegaly.His stretched penile length was 2 cm.Testicular volume was 2 mL.SMR was Tanner stage 1.On eye examination, visual acuity was 6/36 in both eye.Anterior segment was normal.There was retinitis pigmentosa on both eye.Color fundus photography showed generalized pigmented fundus, maculopathy, arterial attenuation.There were some bony spicule in the periphery (Figure 3).Psychiatric evaluation revealed moderate mental retardation, IQ was 50.CVS examination showed no abnormality.
Routine examinations including CBC, urine analysis, X-ray chest, ECG and echocardiography were normal.Bone age was approximately 8-9 years which was lower than his chronological age (Figure 4).Ultrasonography of whole abdomen revealed hepatomegaly with fatty change and both kidneys were normal.Hearing screening was normal.Biochemistry revealed normal creatinine, raised TG (1299 mg/dL) and ALT (151 U/L).Fasting blood sugar was 24.8 mmol/L.After 2 hours of glucose intake, it was 34 mmol/L.Thyroid stimulating hormone was within normal limit.
We diagnosed the case as Bardet Biedl syndrome as our patient had 4 primary and 5 secondary features.
As there is no specific curative therapy available for this syndrome.The boy was managed symptomatically.Genetic counseling was done.The patient was discharged with diabetic diet,

Abstract
The Bardet-Biedl syndrome is a rare genetically heterogeneous, autosomal recessive inherited disorder with wide variability in expression.It presents with varied clinical manifestations like retinitis pigmentosa, polydactyly, central obesity, mental retardation and renal dysfunction.Other rare manifestations include diabetes mellitus, heart disease, hepatic fibrosis and neurological manifestations.Mutations in 16 genes have been identified as causative factors.We, here, have presented a 12 year old male patient exhibiting characteristic features of Bardet Biedl syndrome.

Article Info
Depa  12 Among them, BBS1 and BBS10 are the two main genes involved in BBS and each of this gene mutation is present in more than 20% of the cases. 12The detailed biochemical mechanism that leads to Bardet-Biedl syndrome is still unclear.It is caused by defects in the cellular ciliary structure and hence it is a ciliopathy. 13he first known case was reported by Laurence and Moon in 1886 and there was a controversy in medical literature with the condition described by Laurence and Moon, referred as Laurence-Moon syndrome.After 22 years of prospective cohort study of Newfoundland families with Bardet-Biedl syndrome, Moore et al concluded that Bardet-Biedl syndrome and LMS are different spectrum of same entity. 14Bardet-Biedl syndrome 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. 15,16e primary and secondary features of Bardet-Biedl syndrome are given in Table I.The diagnosis of Bardet-Biedl syndrome can be made if four primary, or three primary and two secondary following features are observed. 2r patient had retinitis pigmentosa and decreased visual acuity.Retinitis pigmentosa is one of the hallmarks of this disorder and found occasionally in the first decade but usually present in almost all patients by second decade.Decreased visual acuity can result from macular involvement of the disease.The patient was obese with hepatomegaly which was may be due to fatty change of liver.He had dyslipidemia associated with obesity.Obesity present in 75% of patients usually begins in the childhood and the severity increases with age. 2 Cause of obesity is unknown but appears to be the effect of a combination of hyperphagia and altered disposal of calories. 2arning disability is a primary feature of BBS, our patient had learning disability probably due to moderate mental retardation and decreased visual acuity.Limb deformities have been reported at varying frequencies.Of these, polydactyly, and brachydactyly of both hands and feet are most common. 2Our patient had moderate mental retardation, IQ is 50 which is a more disputed feature of BBS.An IQ of 79 or below is found in 44% of BBS patients.The decrease in IQ level correlates with the presence of visual handicap. 2,17Hypo-genitalism is reportedly more frequently present in Bardet-Biedl syndrome males than females. 2 Bardet-Biedl syndrome males have small penis and testes (88%). 17ur patient was prepubertal with stretched penile length was 2 cm, testicular volume was 2ml and SMR was Tanner stage 1.
A wide range of renal abnormalities such as chronic renal failure, parenchymal cysts, calyceal clubbing, fetal lobulation, scarring, unilateral agenesis, dysplastic kidneys, renal calculi, vesico-ureterix reflux has been described but our patient had no
Diabetes mellitus is diagnosed in 32-45% of cases with Bardet-Biedl syndrome. 18,19It is usually noninsulin dependent diabetes but occasionally insulin -dependent. 18,20Our patient had diabetes mellitus and was controlled by oral hypoglycemic drugs.Hussain et al. (2000) 4 reported a case of Bardet-Biedl syndrome in our country in a twelve year old boy having all the cardinal features such as obesity, mental deficiency, polydactyly, syndactyly, retinopathy, genital hypoplasia and renal anomalies. 4ur patient had 4 primary features such as polydactyly, retinitis pigmentosa, obesity, learning disabilities and 5 secondary features such as diabetes mellitus, speech & developmental delay, brachydactyly, high arch palate but no renal anomalies.
Diagnosis of Bardet-Biedl syndrome is mainly based on characteristic clinical features.Investigations are done to assess the features that may help in the diagnosis.Genotyping of Bardet-Biedl syndrome may not always be required to make the diagnosis as it is not available at all places specially developing countries like Bangladesh.
For management of Bardet-Biedl syndrome a multidisciplinary approach is needed.Regular monitoring of renal, liver, glucose, lipid and endocrine profile is necessary.Attention should be given to blood pressure and weight management along with regular ophthalmological examination.Visual aids, special schools and educational programs to overcome learning disabilities are important.Speech therapy, behavioral therapy and hormone replacement therapy are required in many cases.Surgical removal of accessory digits may be necessary for cosmetic purpose.

Conclusion
Many progresses have been made about this disease.Further studies are needed to understand the pathophysiology and genetic complexity of the disease.Though the disease is incurable, careful evaluation and symptomatic management may provide good prognosis.

Figure 1 :
Figure 1: Shows central obesity and polydactyly upper limb

Figure 2 :Figure 3 :
Figure 2: Shows polydactyly of both upper limb and lower limb

Figure 4 :
Figure 4: X-ray left hand including wrist joint including hand showing delayed bone age

Table I Features of Bardet-Biedl syndrome
renal abnormalities.Renal failure is the major cause of morbidity and early mortality in Bardet-Biedl syndrome and 25% die by the age of 44 years.