Bardet Biedl syndrome (BBS) is a group of rare disorders characterized by renal failure, loss of vision, polydactyly, obesity, intellectual disability, developmental delay, abnormalities of the genitalia, and poor coordination. Based on the genes/loci associated with each type, BBS is classified into 21 types - BBS1 to BBS21. BBS is rare, affecting only about one in 150,000 individuals in North America and Europe. However, among Arabs, the prevalence rate is much higher, at about one in 13,500 individuals, suggesting a founder effect.
BBS is inherited in an autosomal recessive manner. A digenic mode of inheritance has also been reported. The protein products of most of the genes associated with BBS have been found to be localized to the basal body and centrioles of the cell. This indicates the involvement of these proteins in the cell signalling pathway mediated by cilia, as well as the intraflagellar transport of proteins along the cilia. Mutations in these genes disrupt associated pathways and processes, leading to the varied clinical features seen in the patients.
Al-Arrayed and Al-Arrayed (1991) reported a consanguineous Bahraini family in which two male siblings were affected by BBS. Six other siblings were normal, and the family did not have any previous history of the disease. The elder patient was 25 years of age, whereas the younger one was 18-years old. Both patients were short, obese, and had polydactyly in the hand and feet. Visual acuity was reduced in both brothers. Fundus examination showed narrow retinal vessels with mild to moderate tapetoretinal degeneration in mid periphery, along with retinitis pigmentosa. In addition, the elder brother had a pilonidal sinus, which was earlier excised. He was also hard of hearing and showed cardiomegaly in the chest X-rays, and hepatomegaly in the abdominal ultrasound. Genital examination revealed a short phallus, in both the patients, and additionally, hypogonadism in the case of the younger brother, evidenced by scanty facial and body hair. Moreover, the younger brother had intellectual disability.
[Al-Arrayed SS, Al-Arrayed HH. Bardet-Biedl syndrome in a Bahraini family. Bahrain Med Bull. 1991; 13(1):38-40.]
Farag and Teebi (1988) indicated that in the Arab population of Kuwait, 26 cases in 15 families were ascertained to have Bardet-Biedl syndrome (20 cases in 13 families) or Laurence-Moon syndrome (6 cases in 2 families). Later, Farag et al. (1989) reported the presence of Bardet-Biedl syndrome in an Arab family with three female siblings including twins. The helpful marker in zygosity determination was found to be concordant for benign acanthosis nigricans in the twins. In the same year, Farag and Teebi (1989) indicated that the prevalence of Bardet-Biedl syndrome among Bedouins of Kuwait is approximately 1 in 13,500. [Farag TI, Teebi AS, AL-Awadi SA, El-Ramly MA. Monozygotic twins concordant for Bardet-Biedl syndrome and benign acanthosis nigricans. Med Principles Pract. 1989; 1: 60-2.]
Kwitek-Black et al. (1993) performed genome-wide analysis in a large inbred Bedouin family by employing pairwise analysis. Linkage with D16S408 locus was found with no recombination and a LOD score of 4.2. The linkage finding was supported furthermore by homozygosity in all affected subjects for marker D16S408 and demonstration of homozygosity mapping through inbred families. In another family, linkage at the same locus was eliminated proposing non-allelic genetic heterogeneity of this disease.
Sheffield et al. (1994) detected Bardet-Biedl syndrome locus on chromosome 3, verified the non-allelic heterogeneity of the disease in Bedouin populations and showed the probability of employing pooled DNA samples from subjects of large kindreds as a resourceful method to homozygosity mapping.
Wright et al. (1994) studied 26 Bedouin families having at least 2 members affected with Bardet-Biedl syndrome (BBS) to investigate the disease linkage to 16q21 and 11q13 regions by using markers covering chromosomes 2, 3, 17 and 18. Presuming homogeneity, the investigation on the 57 affected members demonstrated evidence of linkage to D11S527 locus resulting in a LOD score of 2.72 at a recombination fraction of 0.11. [Wright AF, Bruford EA, Mansfield DC, Riise R, Tommerup N, Jay M, Patton MA, Jeffery S, Taschner PEM, Breuning M, Bleeker-Wagemakers EM, Schinzel A, Barber A, Teague PW. Genetic linkage analysis in 26 families with Bardet-Biedl syndrome. Am J Hum Genet. 1994; Suppl A208(1209).]
Saleh et al. (1998) reported three cases of Bardet-Biedl syndrome (BBS) at Al-Jahra Hospital. Subjects represented three unrelated Bedouin children including a 13 year old boy, 7 year old girl, and 1 year and 9 months old boy all born to healthy consanguineous parents. Subjects underwent hormonal studies that revealed negative endocrinological dysfunction except for the occurrence of hypogonadism. Saleh et al. (1998) suggested early assessment of BBS to manage the symptoms and avoid measures for cases and their families.
[See: Libya > Tayel et al., 1999].
Tayel et al. (1999) reported the first case of familial pericentric inversion (PEI) of chromosome 1 (p36.3q23) in six patients suffering from Bardet-Biedl syndrome (BBS) in Kuwait. The proband, an 11 year old Libyan female, two sibs and three maternal cousins were diagnosed with BBS. Chromosomal analysis of 100 metaphase spreads was employed and to demonstrate PEI of chromosome 1 (p36.3q23) in the proband and affected family members. Tayel et al. (1999) found that the inversion was inherited from the proband's mother and her sister.
The features of Bardet-Beidl syndrome in five prepubertal boys were described by Soliman et al. (1996), who also studied their hypothalamic-pitutary function. All five children were found to have some degree of intellectual disability, retinal dystrophy, polydactyly/syndactyly, small testes with short penis and obesity. Pseudo-acanthosis nigricans was found in four of them, three had unilateral cryptorchidism and one of them had hypospadius, two had renal disease with impairment and hypertension. Two brothers were found to have calyceal clubbing in intravenous pyleography and impaired renal function which was rapidly progressive (membranoproliferative glomerulonephritis with interstitial fibrosis on renal biopsy) in one, who then required renal transplantation at the age of 12 years. The other sibling had interstitial infiltration and fibrosis on renal biopsy and pyelography revealed mild vesicoureteric reflux in addition to the calyceal clubbing. Anthropometric measurements revealed short stature in three children and only one of them had slow annual growth velocity below the fifth percentile. Delayed bone age was found in four children. All children were found to have low serum testosterone, and normal but not exaggerated LH and FSH responses to LH-releasing hormone with no high basal levels of FSH. Soliman et al. (1996) concluded that children with BBS had a dual defect of the hypothalamic-pitutary-testicular axis as they showed primary hypogonadism with inappropriately normal basal and LHRH-stimulated gonatotrophin levels, indicating hypothalamic/or pituitary dysfunction.
Rajab et al. (2005) undertook a study to estimate the prevalence of commonly diagnosed autosomal recessive diseases in Oman from a hospital-based register in years 1993 to 2002. The study revealed that BBS was diagnosed in 14 patients, with an observed incidence of 1 in 30,000 births.
Cherian et al. (2008) described two siblings with Bardet Biedl Syndrome in comorbid association with Hirschsprung's Disease. The consanguineous Saudi parents had three other children affected with BBS, but without Hirschsprung's disease. The first of the reported patients was a baby boy, who showed bilateral postaxial polydactyly in all four extremities. He was diagnosed with BBS based on the family history. By 24-days of age, the infant had severe constipation and abdominal distension. Abdominal X-ray revealed long segment variety of Hirschsprung's disease involving the whole colon and terminal ileum. An ileostomy was performed at the ganglionic site, but the patient died of post-operative complications at 27-days of age. His sister was born after a few years with a right preauricular skin tag, right-sided accessory nipple, bilateral brachydactyly, and postaxial polydactyly of hands and feet. She was also diagnosed with BBS. Abdominal X-ray in her case showed dilatation of predominantly colon loops and paucity of gas in the rectum. Motor and social milestones were delayed. She developed nystagmus at 2-years of age and showed rod-cone dystrophy at 4-years of age. Surgical intervention was refused by the parents, till 5-years of age, when she underwent laparotomy, bowel decompression, and ileostomy.
Levy et al. (1970) reported three cases of Laurence-Moon-Biedl-Bardet syndrome in a Jewish Yemenite family. No further details could be obtained as of date.