Laboratory investigations indicated a prepubertal pattern of luteinizing hormone and follicle-stimulating hormone levels with a suppressed testosterone level suggestive of hypogonadotropic hypogonadism. The thyroid function tests and the basal and stimulated growth hormone levels were normal. Ultrasonography abdomen (with kidney ureter bladder) was normal; echocardiography and BAER study did not show any significant abnormality. All other investigations were found to be normal.
Our patient had a 14-year-old twin brother with a similar presentation of nystagmus and pigmentary retinopathy, mild central obesity, male hypogonadism (microtestis and microphallus on genital examination), mental retardation, and postaxial polydactyly of all four limbs. His laboratory data were essentially similar, except for the presence of a normal glycemic index.
According to the clinical and laboratory evidence, our patient was diagnosed with BBS with type I DM. His brother was also diagnosed with BBS but was euglycemic.
The variable manifestations of BBS were initially described by Bardet and Biedl in 1920. It is clearly different from a condition reported by Lawrence and Moon in 1865. BBS is genetically heterogeneous, with 15 BBS genes identified to date (OMIM, ID: 209900). Although the cellular mechanisms that underlie BBS remain unclear, it is now clear that all of the known BBS proteins are components of the centrosome and/or the basal body and have an impact on ciliary transport (Hichri et al., 2005). BBS is a rare disorder, 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 (Katsanis et al., 2001).
BBS is characterized by the following major associations: early-onset retinal dystrophy, obesity, limb-abnormalities, mental retardation, hypogonadism, and renal disease. In addition to the major diagnostic features of BBS, multiple minor features have been also documented in patients at varying frequencies. These include developmental delay, speech and language deficit, psychosis, facial dysmorphism, multiple pigmented nevi (10 patients, of whom eight were females, with multiple widespread pigmented nevi), neurological abnormalities, hearing loss, metabolic and endocrine disturbances including DM, cardiovascular anomalies, disturbances of dentition and liver function, atresia ani, and Hirschsprung disease.
The Arab literature has a number of reports of BBS in siblings. Al-Arrayed and Al-Arrayed (1991) reported a consanguineous Bahraini family in which two male siblings were affected by BBS (Al-Arrayed and Al-Arrayed, 1991). Farag and Teebi (1988) reported the presence of BBS in an Arab family with three female siblings including twins (Farag and Teebi, 1988). The helpful marker in the determination of zygosity was found to be concordant for benign acanthosis nigricans in the twins. Wright et al. (1994) studied 26 Bedouin families with at least two members affected with BBS to examine the disease linkage to 16q21 and 11q13 regions using markers covering chromosomes 2, 3, 17, and 18. Assuming homogeneity, the investigation of the 57 affected members indicated evidence of linkage to the D11S527 locus and an LOD score of 2.72 was obtained at a recombination fraction of 0.11 (Fujita et al., 1996). Balci (2007) reported a Saudi Arabian family with three cases of BBS, two of whom were presumably identical twins (Balci, 2007). However, reports of the disease in identical twins are very rare from other regions of the world.
The association of BBS with type I DM is another unique and extremely rare occurrence worldwide. To date, only Escallon et al. (1989) have reported a family with the BBS and DM. Two affected brothers and one affected sister were examined. Of the three, the 18-year-old brother was obese, had mental retardation, and had pigmentary retinopathy and insulin-dependent DM (Escallon et al., 1989). Whether the association of type1 DM with BBS is causal remains to be explored. Given the highly pleomorphic genetic make-up of BBS and the extremely strong influence of genetic mutations on the causality of type 1 diabetes, the association between the two cannot be dismissed as mere coincidence. However, animal studies on this issue are not forthcoming, neither is evidence from humans adequate. Further genetic studies in future might provide a clue to this intriguing association.
Our case is thus unique because of the extremely rare association of BBS with type I DM in one of the two affected twin brothers. We believe that our case is the first of its kind to be reported from India and this extremely uncommon association adds a new dimension to the pleomorphic nature of this rare genetic syndrome.
Close monitoring of the glycemic parameters in patients with BBS from an early age is highly recommended and the possibility of type I DM should always be kept in mind in a patient with BBS presenting with hyperglycemia.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2012 Middle East Journal of Medical Genetics
Bardet–Biedl syndrome; identical twin brothers; polydactyly; retinopathy; type 1 diabetes mellitus