Bardet-Biedl Syndrome (BBS) is a rarely seen autosomal recessive transfer disease characterised by retinal dystrophy, obesity, extremity deformities, mental retardation, and renal and genital system anomalies. BBS shows heterogenic transfer. To date, 18 genes (BBS1–18) and 7 BBS proteins have been defined as related to BBS. All of the defined BBS genes have been shown to be related to the biogenesis or function of cilia. Renal failure accompanying the syndrome, especially in the advanced stages, is the most common cause of mortality. Therefore, as one of the major diagnostic criteria, renal damage is of great importance in early diagnosis. This paper presents the cases of two brothers with BBS who presented with chronic renal failure.
Bardet-Biedl syndrome (BBS) is a genetic syndrome with autosomal recessive transfer, characterised by retinal dystrophy, obesity, extremity deformities, mental retardation, and renal and genital system anomalies. Apart from these typical findings, various anomalies such as speech defects, dental anomalies, anosmia, cardiac anomalies, diabetes mellitus, hepatic fibrosis, anal agenesis, Hirschsprung disease, and neurological involvement may be seen together with the syndrome. Renal failure accompanying the syndrome, especially in the advanced stages, is the most common cause of mortality. Therefore, as one of the major diagnostic criteria, renal damage is of great importance in early diagnosis. In this report, the typical findings of the disease considered in two brothers with BBS who presented with chronic renal failure and the importance of family scanning are emphasised.
A 41-year-old male applied to the emergency department with complaints of diarrhea, nausea, and vomiting (Figure
External appearance of the cases; (a) Case 1, (b) Case 2.
The patient had height of 159 cm, body weight of 72.5 kg, and BMI of 28.5 and vital signs were normal. The physical examination revealed mental retardation, speech defects, apathetic facial appearance, corneal matte appearance, strabismus, central obesity, micropenis, syndactyly, and polydactyly. The HOMA index was calculated as normal (2.18) for the patient who had central obesity. No pathology was observed from tests in respect of hormonal parameters.
In respect to cardiac pathology, left ventricle function was evaluated as normal on the echocardiography. A moderate level of mental retardation (IQ: 35–49) was determined in the psychiatric evaluation. There was polydactyly in both hands and feet and syndactyly of fingers 3–5 on the left hand (Figure
Extremities of the cases. (a) Polydactyly and syndactyly together in the left hand of Case 1, (b) polydactyly in the left foot of Case 1, and (c) and (d) right hand and foot of Case 2 (areas of previous surgery indicated by the arrow).
Hypogenitalism of the cases. (a) Micropenis and undescended left testis in Case 1. (b) Micropenis in Case 2.
The 38-year-old male had a height of 165 cm, a weight of 70 kg, and BMI of 25.7 and vital signs were normal (Figure
In the hormonal tests done because of hypogenitalism (micropenis) (Figure
In Bardet-Biedl syndrome (BBS), apart from the major findings, different clinical effects can be observed evaluated under the heading of minor criteria, such as speech defects, dental anomalies, anosmia, ataxia, diabetes mellitus, and cardiac anomalies. Rod-cone dystrophy (90–100%), obesity (72–92%), polydactyly (63–81%), genital anomalies (59–98%), learning difficulties (50–61%), and renal anomalies (20–53%) are the major components of BBS. Speech disorders (54–81%), developmental delay (50–91%), diabetes mellitus (6–48%), dental anomalies (51%), congenital heart disease (7%), brachydactyly/syndactyly (46–100%), ataxia/poor coordination (40–86%), cardiopathy (10%), deafness (11–12%), and anosmia/hyposmia (60%) are the minor components of BBS [
While the underlying pathology of BBS clinical findings remains unknown, the study results of several subjects have suggested that the basic reason for this pleiotropic disease originates from basal body or cilia dysfunction [
BBS clinical characteristics generally start to be seen slowly in the first decade of life. Most cases are diagnosed in late childhood or early adolescence. Extremity anomalies determined at birth are one of the most important clinical signs for diagnosis. In terms of indicating diagnosis, extremity or renal anomalies at birth or in the intrauterine period are important. However, the variability which can be seen in these two characteristics and the late onset of other indications may be the reason for the diagnosis of the cases after childhood.
BBS is one of the most important causes of syndromic retinal dystrophy, which is seen with severe sight problems during preadolescence and with generally total loss of vision before the second decade [
In BBS cases, obesity, especially central obesity, is the second major clinical finding in terms of significance and prevalence. Rates of obesity incidence have been reported as 72–92% in BBS cases. While birthweight is generally normal, 1 in 3 syndromic babies with normal birthweight becomes obese before the age of 1 year [
Extremity anomalies such as polydactyly and syndactyly as the earliest seen signs in BBS patients which are determined at birth are one of the most important clinical indicators for diagnosis. Typically, polydactyly is seen in 63–81% of BBS cases. As it is seen from birth onwards, it is the most important finding for suspicion of the syndrome [
Hypogonadism as another major criterion of the syndrome may be seen with delayed onset of puberty in both genders, hypogenitalism in males and genital anomalies in females. Gonadal dysfunction is seen more often in male patients than female patients. Small penis size and decreased testis volume are often seen in male patients and in female patients; there is often a delay in the onset of the menstrual cycle. In female patients, hypoplasia of the fallopian tubes, uterus, and ovaries, vaginal atresia, and genital malformations such as hematocolpos and vesicovaginal fistula may be seen.
Mental retardation, learning difficulties, speech defects, autism, and behavioural problems such as psychosis are neuropsychiatric impairments seen in BBS. Mental retardation is the fourth most important characteristic of the syndrome. Psychosocial development is retarded and IQ test scores are low. Cognitive dysfunction is noticed in most cases after they start school. It has been shown that primary cilia are one of the most important organelles in the human brain and are necessary for the hippocampal development stages. It has been shown in a study that the hippocampus volume of BBS cases is low in comparison with healthy individuals [
Urogenital system malformations are common in BBS and all cases should be routinely investigated for renal anomalies. The onset of renal dysfunction has not been evaluated as a major component of the syndrome. However, in the subsequent period, the observation of renal involvement in most cases and that it is the most common cause of mortality causes renal dysfunction to be defined as a major criterion of the syndrome [
Although a range of renal anomalies may be seen, the classic appearance is tubular disease and anatomic malformations. Renal symptoms are generally nonspecific. In approximately a third of cases, polyuria/polydipsia is seen to be associated with defective vasopressin-resistant urine concentration [
The most commonly seen renal function impairment is impaired urine concentration capacity. In most cases of the urine concentration defect, no deterioration in renal function tests is observed [
In kidney histology, chronic interstitial nephritis, mesangial proliferative glomerulopathy, and structural changes in the glomerular basal membrane may be observed. In some cases, advanced renal failure may develop due to cystic kidney disease. This may cause recurrent urinary system infections, chronic pyelonephritis, and kidney failure. As radiological findings in addition to renal function impairments in BBS patients, structural renal defects may be seen such as renal cysts, diverticulae, calyceal deformity, fetal lobulation, scars, and diffuse cortical loss.
An effective multidisciplinary approach is required to manage this pleiotropic situation. There is no definitive treatment method for BBS. Complications related to BBS should be treated symptomatically. There should be an awareness of complications for which BBS has laid the base and patients should be followed up in this respect. Effective weight management is necessary to prevent related morbidities such as metabolic syndrome. Patients with metabolic syndrome should be evaluated in respect to potential hypertension, diabetes mellitus, hyperlipidemia, and cardiovascular diseases. A detailed ophthalmological evaluation including electroretinogram (ERG) is required to determine the onset and extent of retinal dystrophy. Renal ultrasound should be applied to all patients at the time of diagnosis to discount renal malformation. Patients with findings of chronic renal failure should be referred to a nephrologist. Developmental and educational evaluations are necessary for all patients [
BBS generally shows autosomal recessive inheritance. Although triallelic inheritance has been reported in some cases, it is difficult to determine as it is seen in less than 10% of all cases. Information should be given about the heterogeneous nature of the patients and their relatives. In families who know the mutation causing the disease, there is the possibility of preimplantation genetic diagnosis or prenatal testing. In families at risk whom the mutation is unknown to, ultrasonography can be applied in the third trimester for the visualization of axial polydactyly and renal malformations [
For patients presenting with impaired kidney function accompanied by findings such as polydactyly, mental retardation, obesity, vision problems, or micropenis, BBS should certainly be considered.
However, the syndrome is rarely observed; kidney involvement is common.
When it is considered that renal failure is the most common cause of mortality, early diagnosis of renal damage is of great importance.
The syndrome and renal damage can be determined in early stages by family scanning.
The authors declare that there is no conflict of interests regarding the publication of this paper.