A review of the literature of Bardet–Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty

Abstract

Bardet-Biedl syndrome (BBS) is a genetic autosomal-recessive disease (formerly grouped with Laurence-Moon-Biedl syndrome but considered today as a separate entity) characterized by abdominal obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism or hypogenitalism (limited to male patients) and kidney structural abnormalities or functional impairment. The expression and severity of the various clinical BBS features show inter- and intrafamilial variability. This study focuses on three cases of familial BBS--two sisters and one brother (66, 64 and 51 years of age, respectively)--with the main cardinal findings of the disease plus a classic 'metabolic syndrome' (characterized by abdominal obesity, atherogenic dyslipidaemia, raised blood pressure, insulin resistance with or without glucose intolerance, and prothrombotic risk and proinflammatory states). One female patient (not affected by reproductive dysfunction) had three healthy offspring, while the other two patients were unmarried. Another severely affected brother died at 70 years of age; two other brothers are lean but affected by nephropathy, retinopathy, slight mental retardation, polydactyly, hypertension and thrombotic diseases, and had healthy offspring. BBS is a rather rare but severe syndrome that is often mis- or undiagnosed. Ophthalmologists, endocrinologists and nephrologists should be aware of BBS because of its adverse prognosis--early onset of blindness, associated findings of metabolic syndrome and increased vascular risk, and severe renal impairment (the most frequent cause of reduced survival and death early in life).

Bardet-Biedl Syndrome Gene Variants Are Associated With Both Childhood and Adult Common Obesity in French Caucasians

“…Obese children who were homozygous for the BBS6 variant rs221667 also had significantly higher postprandial glycemia. Dyslipidemia and hyperglycemia have been described as major risk factors for the metabolic syndrome, a previously described component and associated complication of BBS (36).…”

Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick–Kaufman syndrome gene variants are associated with metabolic syndrome

“…Mutations in MKKS cause Bardet-Biedl syndrome, which is an autosomal recessive mendelian disorder characterized by progressive obesity, retinal dystrophy, learning disability, polydactyly, renal and cardiac malformations and hypogenitalism. 23,24 In some cases of Bardet-Biedl syndrome, the patients also had metabolic syndrome, 25 and MKKS-null mice developed obesity and hypertension in addition to the phenotype resembling that of the Bardet-Biedl syndrome. 26 Recently, T variant of rs6108572 was reported to be associated with quantitative components of the metabolic syndrome (dyslipidemia) as well as obesity and in French Caucasian children.…”

Bardet–Biedl syndrome associated with glaucoma

“…Furthermore, deafness is found in approximately 5% of BBS patients, polydactyly may be seen in AHS patients and renal involvement, which is considered an important feature of BBS, may also be present in AHS, but generally it is diagnosed later in life (usually after 16 years of age). 1,5,6 Unfortunately, in the paper of Klein and Ammann, 1 there was lack of information about the biomicroscopic and gonioscopic findings of the eyes of the two patients reported with the AHS-glaucoma association. These authors described the glaucoma as 'juvenile familialtype'.…”