Diffusion tensor imaging for the study of early renal dysfunction in patients affected by bardet-biedl syndrome.

Kidney structural abnormalities are common features of Bardet-Biedl syndrome (BBS) patients that lead to a progressive decline in renal function. Magnetic resonance diffusion tensor imaging (DTI) provides useful information on renal microstructures but it has not been applied to these patients. This study investigated using DTI to detect renal abnormalities in BBS patients with no overt renal dysfunction. Ten BBS subjects with estimated glomerular filtration rates over 60 ml/min/1.73m2 and 14 individuals matched for age, gender, body mass index and renal function were subjected to high-field DTI. Fractional anisotropy (FA), and mean, radial and axial diffusivity were evaluated from renal cortex and medulla. Moreover, the corticomedullary differentiation of each DTI parameter was compared between groups. Only cortical FA statistically differed between BBS patients and controls (p = 0.033), but all the medullary DTI parameters discriminated between the two groups with lower FA (p < 0.001) and axial diffusivity (p = 0.021) and higher mean diffusivity (p = 0.043) and radial diffusivity (p < 0.001) in BBS patients compared with controls. Corticomedullary differentiation values were significantly reduced in BBS patients. Thus, DTI is a valuable tool for investigating microstructural alterations in renal disorders when kidney functionality is preserved.

Bardet-Biedl syndrome-7 (BBS7) shows treatment potential and a cone-rod dystrophy phenotype that recapitulates the non-human primate model.

Purpose: To provide a detailed ophthalmic phenotype of two male patients with Bardet-Biedl Syndrome (BBS) due to mutations in the BBS7 geneMethods: Two brothers ages 26 (Patient 1, P1) and 23 (P2) underwent comprehensive ophthalmic evaluations over three years. Visual function was assessed with full-field electroretinograms (ffERGs), kinetic and chromatic perimetry, multimodal imaging with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation lights and adaptive optics scanning light ophthalmoscopy (AOSLO).Results: Both siblings had a history of obesity and postaxial polydactyly; P2 had diagnoses of type 1 Diabetes Mellitus, Addison's disease, high-functioning autism-spectrum disorder and -12D myopia. Visual acuities were better than 20/30. Kinetic fields were moderately constricted. Cone-mediated ffERGs were undetectable, rod ERGs were ~80% of normal mean. Static perimetry showed severe central cone and rod dysfunction. Foveal to parafoveal hypoautofluorescence, most obvious on NIR-FAF, co-localized with outer segment shortening/loss and outer nuclear layer thinning by SD-OCT, and with reduced photoreceptors densities by AOSLO. A structural-functional dissociation was confirmed for cone- and rod-mediated parameters. Worsening of the above abnormalities was documented by SD-OCT and FAF in P2 at 3 years. Gene screening identified compound heterozygous mutations in BBS7 (p.Val266Glu: c.797 T > A of maternal origin; c.1781_1783delCAT, paternal) in both patients.Conclusions: BBS7-associated retinal degeneration may present as a progressive cone-rod dystrophy pattern, reminiscent of both the murine and non-human primate models of the disease. Predominantly central retinal abnormalities in both cone and rod photoreceptors showed a structural-functional dissociation, an ideal scenario for gene augmentation treatments.

Acute myocardial infarction and haemodynamic stroke in a young patient with Bardet-Biedl syndrome.

A 28-year-old man diagnosed with diabetes mellitus and systemic hypertension presented with a medical history of sudden onset retrosternal discomfort followed by loss of consciousness and generalised tonic clonic seizures. Examination revealed obesity, polysyndactyly and retinal pigment dystrophy. He was diagnosed to have acute myocardial infarction and left posterior watershed infarct. He was also diagnosed to have Bardet-Biedl syndrome based on clinical features. He was managed symptomatically and is currently doing well on regular follow-up in the outpatient clinic.

Prenatal Diagnosis of Hydro(metro)colpos: A Series of 20 Cases.

BACKGROUND: Hydrocolpos and hydrometrocolpos are rare malformations caused by accumulation of secretion due to congenital obstruction of the vagina. Hydro(metro)colpos may be isolated or can be combined with other malformations as part of a syndromic disorder. We report on a series of 20 cases with hydro(metro)colpos diagnosed prenatally, delineate the differential diagnoses, and illustrate the spectrum of associated malformations. SUBJECTS AND METHODS: This was a retrospective study involving 20 fetuses with hydro(metro)colpos at two large tertiary referral centers in Germany over an 18-year period (2000-2017). RESULTS: The median diagnosis was made at 30+4 weeks of gestation, the earliest at 20+6 weeks, the latest at 37+2 weeks. All 20 fetuses presented with the typical cystic structure behind the fetal bladder. Additional malformations included urogenital malformations, hexadactyly, and heart defects. Postnatal follow-up revealed that hydro(metro)colpos was associated with anorectal malformation in 11/20 fetuses, McKusick-Kaufman syndrome or Bardet-Biedl syndrome in 4/20 fe tuses, Mayer-Rokitansky-Küster-Hauser syndrome in 3/20 fetuses, and Herlyn-Werner-Wunderlich syndrome in 1/20. In 1 fetus pressure from an intraabdominal teratoma resulted in prenatal hydro(metro)colpos. CONCLUSION: Hydro(me tro)colpos is a rare prenatal sonographic feature. Multidisciplinary prenatal counseling should include all potential syndromes that can present with hydro(metro)colpos in the prenatal setting.

Anesthetic considerations for patients with Bardet-Biedl syndrome: a case series and review of the literature.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic condition with manifestations that can impact anesthetic and perioperative care. There is a void of literature describing the perioperative anesthetic management in this complex patient population. OBJECTIVES: The purpose of this retrospective series was to describe the perioperative care of patients diagnosed with BBS at a large academic tertiary referral center with experience in caring for these patients. METHODS: All patients receiving anesthesia during the time between July 10, 1997 and Jan 1, 2015 were identified. Anesthetic and perioperative records were reviewed in detail for demographic, echocardiographic, preoperative, intraoperative, and postoperative data. RESULTS: We identified 12 patients with BBS undergoing 40 anesthetics at our institution. The study identified a high risk for difficult airway with need for advanced airway techniques (67% of patient's ≥ 18 years of age required either awake fiberoptic or video laryngoscopy techniques), cardiac abnormalities, renal impairment, morbid obesity, and intellectual disability as the main syndrome manifestations of interest to the anesthesiologist. No patient had perioperative complications directly related to BBS; however, each underwent thorough perioperative evaluation with emphasis on the systemic comorbidities associated with the syndrome. This report illustrates that patients with BBS can safely undergo anesthesia, but a detailed and often multidisciplinary preoperative evaluation is prudent.

Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome.

Olfactory bulb (OB) volume evaluation by magnetic resonance imaging (MRI) has been demonstrated to be related to olfactory dysfunction in many different diseases. Olfactory dysfunction is often overlooked in Bardet-Biedl syndrome (BBS) patients and is rarely objectively evaluated by MRI. We present a series of 20 BBS patients with olfactory dysfunction. The OB was evaluated separately and blindly by two radiologists (SR and SM) with 3 Tesla MRI imaging comparatively to 12 normal control subjects by global visual evaluation and by quantitative measurement of OB volume. In the 12 control cases OB visual evaluation was considered as normal in all cases for radiologist (SR) and in 10 cases for radiologist (SM). In the 20 BBS patients, OB visual evaluation was considered as abnormal in 18 cases for SR and in all cases for SM. OB volumetric evaluation for SR and SM in BBS patients was able to provide significant correlation between BBS and olfactory dysfunction. This study indicates that OB volume evaluation by MRI imaging like structural MRI scan for gray matter modifications demonstrates that olfactory dysfunction in BBS patients is a constant and cardinal symptom integrated in a genetical syndrome with peripheral and central olfactory structure alterations.

Radiologic and hormonal evaluation of pituitary abnormalities in patients with Bardet-Biedl syndrome.

To describe the structural changes in the pituitary gland and accompanying pituitary hormonal problems in patients with Bardet-Biedl syndrome (BBS), 11 patients with BBS (median age: 12.8 years, range: 2.5-17.8 years; four boys and seven girls) have been examined for the anomalies of the pituitary region detected by MRI. Accompanying clinical, biochemical, and hormonal profiles concerning the pituitary function of the patients have also been investigated. We have found a high incidence of pituitary anomalies on MRI (63%) and a considerable percentage of hormonal derangements (45%) accompanying these. Among the structural pituitary abnormalities, tumoral changes (n=2), hypoplastic hypophysis, and/or sella (n=4) and rathke cleft cyst (n=2) were detected, whereas disturbances of the pituitary hormones such as growth hormone deficiency, hyperprolactinemia, hypogonadotrophic hypogonadism, and central precocious puberty accompanied the pituitary anomalies in these patients. Pituitary abnormalities and pituitary hormonal dysfunction are common findings and, therefore, should be included in the diagnostic criteria of BBS.

[Prenatal diagnosis of hyperechogenic kidneys: A study of 17 cases]. / Diagnostic anténatal des reins hyperéchogènes : à propos de 17 cas.

OBJECTIVES: To evaluate the prenatal diagnosis and the prognostic value of ultrasound in case of fetal hyperechogenic kidneys. PATIENTS AND METHODS: Seventeen prenatally diagnosed cases of hyperechogenic kidneys were retrospectively reviewed at the University Hospital of Lille from 1997 to 2008. The clinical and ultrasound data were compared to the postnatal follow-up and the long-term prognosis. RESULTS: The aetiologies are nine recessive polycystic kidney diseases, three dominant, two Bardet-Biedl syndromes and three cases of transient renal hyperechogenicity. No renal ultrasonographic criterion is specific of aetiology. Five pregnancies were terminated. We observed one neonatal death and 11 survivors (median follow-up: 30months) including two infants with hypertension. All oligohydramnios (n=8) were associated with poor prenatal outcomes (terminations of pregnancy, neonatal death or hypertension) compared to the other nine with normal amniotic fluid volume (nine children symptom-free). Kidneys less or equal to +4 S.D. and a normal amniotic fluid volume were associated with a good prognosis (n=7, seven symptom-free). CONCLUSION: The fetal kidneys characteristics on prenatal ultrasound fail to provide an accurate etiological diagnosis. Only congenital defects and family history adjust the aetiology. Amniotic fluid volume and fetal kidney size are the best prenatal predictors of outcome.

Hydrometrocolpos and acute renal failure: a rare neonatal presentation of Bardet-Biedl syndrome.

The presence of hydrometrocolpos and postaxial polydactyly in a neonate can be caused by two genetic conditions; namely, McKusick-Kaufman syndrome and Bardet-Biedl syndrome. There are no distinct clinical features that allow discrimination between the two syndromes, as the cardinal features of rod-cone dystrophy, obesity, learning disability and renal dysfunction in Bardet-Biedl syndrome are age dependent. McKusick-Kaufman syndrome is characterized by vaginal atresia with hydrometrocolpos, postaxial polydactyly and congenital heart defect. Here we report an unusual presentation of Bardet-Biedl syndrome: a neonate born in a consanguineous family having an older sibling diagnosed with Bardet-Biedl syndrome presenting with postaxial polydactyly and vaginal atresia; the latter causing hydrometrocolpos, hydronephrosis and renal failure. Relief of urinary obstruction by exploratory laparotomy and aspiration of fluid, and vaginal reconstruction gradually reversed the hydronephrosis and renal failure. The patient developed end-stage renal failure towards the end of her first decade, possibly due to underlying renal pathology associated with Bardet-Biedl syndrome.

Differential diagnosis of fetal hyperechogenic cystic kidneys unrelated to renal tract anomalies: A multicenter study.

OBJECTIVES: To identify important factors in the differential diagnosis of renal cysts associated with hyperechogenic kidneys. METHODS: This was a retrospective multicenter study. We identified 93 fetuses presenting between 1990 and 2002 with hyperechogenic kidneys and which had a diagnosis of nephropathy confirmed later. We analyzed retrospectively the prenatal ultrasound findings of those fetuses which were found sonographically to have renal cysts. RESULTS: Of the 93 fetuses presenting with hyperechogenic kidneys and with a later diagnosis of nephropathy, there were 28 with autosomal dominant polycystic kidney disease (ADPKD), 31 with autosomal recessive polycystic kidney disease (ARPKD), 11 with Bardet-Biedl syndrome, nine with Meckel-Gruber syndrome, six with Ivemark II syndrome, one with Jarcho-Levin syndrome, one with Beemer syndrome and one with Meckel-like syndrome. One third of the fetuses (30/93) had renal cysts. Cystic characteristics (size, location, number) were not very useful for diagnosis; more useful was diagnosis of an associated malformation. Three (11%) of the fetuses with ADPKD had cysts, as did nine (29%) of those with ARPKD, three (27%) of those with Bardet-Biedl syndrome, all (100%) of those with Meckel-Gruber syndrome, three (50%) of those with Ivemark II syndrome, and each of the three cases with other syndromes (Jarcho-Levin, Beemer and Meckel-like syndromes). None of the cases with trisomy 13 had cysts. There were no associated malformations in the 12 cases with renal cysts and polycystic kidney disease; the other 18 cases with renal cysts were associated with malformations that were often specific, such as polydactyly in Bardet-Biedl and Beemer syndromes, occipital defect and Dandy-Walker malformation in Meckel-Gruber or Meckel-Gruber-like syndromes, and thoracic and/or vertebral abnormalities in Jarcho-Levin and Beemer syndromes. CONCLUSION: Renal cysts associated with hyperechogenic kidneys are not rare. The clue to diagnosis is the demonstration of an associated malformation. If no malformation is found, the main diagnosis remains polycystic kidney disease, i.e. ARPKD or ADPKD.

Antenatal renal sonographic anomalies and postnatal follow-up of renal involvement in Bardet-Biedl syndrome.

OBJECTIVES: To describe an antenatal sonographic renal pattern encountered in Bardet-Biedl syndrome, a rare autosomal recessive disorder whose definitive diagnosis is often delayed, and to describe the evolution of the sonographic appearance of the kidneys after birth. METHODS: Among a large group of fetuses with hyperechoic kidneys, we retrospectively analyzed the prenatal sonographic findings and clinical and postnatal renal sonographic evolution of 11 patients who were found to be affected by Bardet-Biedl syndrome. RESULTS: All 11 fetuses presented enlarged homogeneously hyperechoic kidneys without corticomedullary differentiation. The diagnosis was established before birth in three fetuses thanks to their familial history. It was confirmed during childhood in the remaining eight based on the development of the classic features of the syndrome. In the postnatal period, the prenatal pattern persisted for a few months in all 11 cases. The sonographic aspects of the kidneys normalized in most cases between 1 and 2 years after birth. CONCLUSIONS: In affected families, the prenatal appearance of enlarged hyperechoic kidneys without corticomedullary differentiation should prompt a diagnosis of recurrence in the family of Bardet-Biedl syndrome, especially when polydactyly is present. In non-affected families, Bardet-Biedl syndrome should be included in the differential diagnosis whenever such an appearance is discovered in utero. The postnatal evolution of the renal sonographic findings is variable and normalization generally occurs by the age of 2 years.

Orthopaedic manifestations of Bardet-Biedl syndrome.

Bardet-Biedl syndrome is an autosomal recessive disorder poorly characterized in the orthopaedic literature. Classic manifestations of the syndrome include pigmentary retinopathy, obesity, polydactyly, hypogonadism, and mild mental retardation. Previous reports have implied that orthopaedic findings are due to an epiphyseal dysgenesis inherent to the syndrome. The purpose of this study was to evaluate the orthopaedic manifestations of 27 patients with this syndrome. Detailed medical histories and physical examinations as well as pedigree analyses and radiographic bone surveys were performed. Orthopaedic findings included the following: 17 patients had postaxial polydactyly, 4 patients had scoliosis, 2 patients had tibia valga, 2 patients had tibia vara, and 1 patient had Legg-Calve-Perthes. The bone survey did not reveal any additional radiographic abnormalities. Based on these results, Bardet-Biedl syndrome patients do not have epiphyseal dysgenesis; their epiphyseal manifestations are probably the result of their obesity.

McKusik-Kaufman syndrome: prenatal diagnosis, genetics and follow up.

McKusick-Kaufman syndrome (MKKS) is a rare autosomal recessive genetic disease with classical hexadactyly and hydrocolpos in females and sometimes cardiac abnormality. We report such a case diagnosed just before birth with a favourable outcome. From this case we describe and discuss all the prenatal sonographic signs which are not always present. On the genetic side, the gene has recently been localized together with the mutation responsible for MKKS. The phenotypic relationship between MKKS which has a good prognosis and Bardet-Biedl syndrome (BBS) with a worse prognosis requires great caution before diagnosing MKKS and a long follow-up is necessary to recognize obesity, growth retardation and pigmentary retinitis.

Prenatal diagnosis of Bardet-Biedl syndrome by targeted second-trimester sonography.

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by mental retardation, obesity, retinal degeneration, polydactyly and syndactyly, diabetes mellitus, hypogenitalism, renal dysplasia and short stature. Definitive molecular diagnosis for BBS is not currently available and counseling of affected families is based on the 25% recurrence risk consistent with autosomal recessive inheritance. Our case presents the first successful use of second trimester targeted sonographic anatomy scanning to prospectively identify a fetus affected with BBS, and indicates that ultrasound can be of critical importance in providing precise as well as timely prenatal diagnosis for families at risk for this serious disorder.

Renal vascular abnormalities in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder. Specific diagnostic criteria for BBS have now been defined. At least four of the five cardinal signs of mental retardation, obesity, hypogenitalism in men, distal limb anomalies, and progressive tapetoretinal degeneration of the retina are required for the diagnosis. Renal involvement has been described as a sixth cardinal feature. Chronic renal failure occurs in 30%-60% of patients. Hypertension has been noted in 50%-66% of cases. Renal abnormalities reflect a defect in maturation of the kidneys. We present a patient with BBS who had bilateral microaneurysms and occlusions in renal arterioles.