Abnormal cone synapses in human cone-rod dystrophy.

OBJECTIVE: Little is known of the cytopathology of photoreceptors in human inherited retinal dystrophies that initially affect the central retina, including the macula. The current study sought to determine the cytologic features of dysfunctional cone and rod photoreceptors, as well as the pattern of degeneration of the cells in representative cases of central retinal dystrophy. STUDY DESIGN: Comparative human tissue study. MATERIALS: Four human donor eyes with the following forms of central retinal dystrophy: cone-rod dystrophy (CRD), central areolar choroidal dystrophy, Bardet-Biedl syndrome, and cone dystrophy-cerebellar ataxia. The cytologic features of retinal photoreceptors in these eyes were compared with those in an eye with retinitis pigmentosa and six normal human eyes. METHODS AND OUTCOME MEASURES: Immunocytochemistry and electron microscopy were used to evaluate the retinal histopathology in the donor eyes. RESULTS: Cone numbers were decreased in the case of CRD, particularly in the central and far peripheral retina, and both cone and rod outer segments were slightly shortened. Occasional degenerate cones had dense cytoplasm and pyknotic nuclei dislocated sclerad to the external-limiting membrane. The most prominent alteration in this retina was marked enlargement and distortion of the cone photoreceptor pedicles, which contained reduced numbers of synaptic vesicles. The retina with central areolar choroidal dystrophy contained a few cones with similarly abnormal synapses. However, comparable cone synapse abnormalities were not observed in the cases of Bardet-Biedl syndrome, cone dystrophy-cerebellar ataxia, retinitis pigmentosa, or in the normal retinas. CONCLUSIONS: The functional consequences of the cone synapse abnormalities in CRD are not known but may correlate with the electroretinographic abnormalities documented in some cases of CRD. To our knowledge, comparable synapse changes have not been noted in either rods or cones in other forms of retinal dystrophy, including retinitis pigmentosa, suggesting that different cytopathologic mechanisms may be involved.

Renal involvement in the Laurence-Moon-Bardet-Biedl syndrome: report of five cases.

We report five patients with Laurence-Moon-Bardet-Biedl syndrome (LMBBS) who had renal involvement. Intravenous pyelography showed bilateral or unilateral calyceal clubbing and blunting in all patients. In addition, one patient had a parapelvic cyst in the left kidney and another had bilateral lobulated renal outlines of the fetal type. One patient had a urinary concentrating defect and two patients showed increased fractional sodium excretion. Estimated tubular phosphate reabsorption values were in normal limits in all of five patients. No patient had a urine acidification defect, proteinuria, glycosuria, or hyperaminoaciduria. One patient died from end-stage renal failure. The remaining four patients had normal serum creatinine values and estimated creatinine clearances. 99mTechnetium-diethylenetriamine pentaacetate renal scanning showed prolonged and delayed concentration and delayed excretion in three of the four patients who survived. A focal scar was determined on the left kidney of one of four patients by 99mtechnetium-dimercaptosuccinic acid renal scanning. All LMBBS cases with or without renal symptoms should be routinely evaluated for renal abnormalities. Renal scanning is a valuable method, especially for determining the renal involvement in the early stage of disease.

Ocular findings in the Laurence-Moon-Bardet-Biedl syndrome.

PURPOSE: To improve the description of the ocular part of the Laurence-Moon-Bardet-Biedl syndrome. METHODS: We examined 44 Scandinavian individuals who all had retinal dystrophy plus at least 2 more of the traditional cardinal signs of the syndrome: obesity, hypogenitalism, polydactyly and mental retardation. RESULTS: Full-field electroretinograms were obtained in 36 of the individuals and were abnormal in all. The dark adaptation thresholds were elevated by on average 3.5 log units. Symptoms of night blindness were observed at a mean age of 4 years and visual problems at daytime at 6-7 years. No one exceeding the age of 16 had a best corrected visual acuity of more than 0.1. In the fundus attenuated vessels were noted at all ages while macular pigmentations and a wax-pale optic disc appeared at age 6-7 years. Pigmentary changes in the midperiphery were noted at the earliest at 13 years of age and appeared mainly as bone spicules, however, in a minority of cases the pigmentations were atypical. Ten of the participants had been followed through a period of 9 years. Their visual acuity was reduced by on average 0.3 line (decimals) and the angle of visual fields by approximate 3 degrees (Goldmann standard object V:4e) per year through the adolescence. CONCLUSION: The ocular disease in Laurence-Mood-Bardet-Biedl syndrome presents early, the prognosis for visual function is poor and the fundus features are atypical and varying.

Anomalies in the permanent dentition and other oral findings in 29 individuals with Laurence-Moon-Bardet-Biedl syndrome.

This paper reports a clinical and roentgenological examination of the teeth, jaws and saliva of 29 Scandinavian individuals with Laurence-Moon-Bardet-Biedl (LMBB) syndrome, whose cardinal signs are retinal dystrophy, polydactyly, obesity, hypogenitalism and mental retardation. All subjects had at least three of these signs, including retinal dystrophy. Compared with normal subjects, the group had statistically significantly higher frequencies of hypodontia, small teeth and short roots. In addition, the saliva showed a buffering capacity higher than normal. In conclusion, there seem to exist disturbances of both dental and skeletal formation in the LMBB syndrome.

Clinical features of Bardet-Biedl syndrome.

Six patients with Bardet-Biedl syndrome who have been followed in our clinics for the last 5 years are reported in this study. Of the five classic features of this syndrome; obesity and mental retardation were present in all cases, retinal disturbances were present in five, polydactyly in three and hypogenitalism was observed in all four male patients. Renal involvement, often suggested as a cardinal feature of this syndrome, was described in two patients. Iron deficiency anemia occurred in three patients, two patients were of short stature, one patient presented with an empty sella, and in two patients clinodactyly was detected. The results are compared to previously published literature and discussed.

Genital abnormalities in females with Bardet-Biedl syndrome.

The major manifestations of the Bardet-Biedl syndrome are digital anomalies, tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism (described mainly in males). We report on 2 girls with Bardet-Biedl syndrome who also had vaginal atresia. A similar association in females with Bardet-Biedl syndrome was suggested in published reports of 11 affected individuals who had structural genital abnormalities, (some of which were missed in childhood), including persistent urogenital sinus, ectopic urethra, hypoplasia of the uterus, ovaries and fallopian tubes, uterus duplex, and septate vagina. The association of atresia of the vagina and other malformations of female genital structures in individuals with Bardet-Biedl syndrome has often been missed in childhood and should be looked for more systematically.

Clinical pathology and retinal vascular structure in the Bardet-Biedl syndrome.

A comparative study of clinical pathology and retinal vascular structure is described as studied by vascular casting in an eye of a patient with the Bardet-Biedl syndrome. At the time of examination the eye had been almost blind for at least 4 years. The histopathological examination showed a largely uniform loss of the outer retinal layers. The gross pathological examination of the cast ocular fundus showed three distinct zones, an inner zone inside the temporal vascular arcades where retinal vessels had been cast, a mid peripheral zone with bone spicules, and a peripheral zone with neither cast vessels nor bone spicules. The findings are discussed in relation to possible pathophysiological mechanisms involved in the development of retinal dystrophy in the Bardet-Biedl syndrome.

Cardiac abnormalities in the Bardet-Biedl syndrome: echocardiographic studies of 22 patients.

The Bardet-Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former "Laurence-Moon-Biedl-Bardet" syndrome. However, since the establishment of the Bardet-Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet-Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome.

Tibia vara in a patient with Bardet-Biedl syndrome.

The Bardet-Biedl syndrome is characterized by polydactyly, hypogonadism, obesity, mental retardation, and retinitis pigmentosa. Several other skeletal findings include hip dysplasia, short stature, and skull deformities. The patient described in this report has the classic findings of Bardet-Biedl syndrome in conjunction with tibia vara and irregular physes of the lower extremities.

[Case report of Laurence-Moon-Bardet-Biedl syndrome]. / Falldemonstration vom Laurence-Moon-Bardet-Biedl-Syndrom.

We report a case of Laurence-Moon-Bardet-Biedl Syndrome with all five recognised features: tapetoretinal dystrophy, polydactily, obesity, mental retardation and hypogonadism. Nevertheless the correct diagnosis was delayed due to the fact, that the patient has a macular dystrophy (instead of a pigmentary retinopathy). He had an operation of the polydactily during childhood. This was not revealed at first. The case underlines the importance of an exact anamnesis of the parents.

Lawrence-Moon-Bardet-Biedl syndrome: a case report.

A case report of the rare Lawrence-Moon-Bardet-Biedl Syndrome in a 10-year old Nigerian boy is presented. The findings were obesity, mental retardation, polydactyly hypogonadism, macula degeneration and retinities pigmentosa.

Glomerulonephropathy of Laurence-Moon-Biedl syndrome.

A patient with Laurence-Moon-Biedl syndrome and nephrotic range proteinuria is presented. Radiological investigation of the urinary tract revealed clubbed calyces but no evidence of obstruction or vesicoureteric reflux. Renal biopsy revealed occasional sclerotic glomeruli, extensive foot-process fusion and segmental glomerular basement membrane abnormalities with negative immunofluorescence for immunoglobulins and complement. Nephrotic proteinuria responded to steroid therapy but mild proteinuria persisted. The findings were consistent with minimal change nephropathy superimposed on the glomerular lesions of Lawrence-Moon-Biedl syndrome.

Sex chromosome aneuploidy and Bardet-Biedl syndrome.

The inheritance of Bardet-Biedl syndrome is thought to be autosomal recessive. Of the approximately 500 case reports in the literature, three patients were found to have sex chromosome aneuploidy. The authors describe two siblings with Bardet-Biedl syndrome, one of whom has a unique sex chromosome aneuploidy with mosaicism, including deletion of the short arm of the X chromosome (45,X/46,X,del(X)(p21)). The possible significance of sex chromosome aneuploidy and the Bardet-Biedl syndrome is discussed.

Sonographic and urographic correlation in Bardet-Biedl syndrome (formerly Laurence-Moon-Biedl syndrome).

To determine the spectrum of urologic disease and the value of ultrasound as a screening mechanism, renal imaging was performed on 23 patients with Bardet-Biedl syndrome. On intravenous urography (IVU), abnormal calices were present in 22 patients, with communicating cortical cysts/diverticula in 17. Ultrasound detected caliceal or cystic changes in 70%. On IVU, 21 patients had fetal-type lobular outlines that were detected on sonography in 95%. Renal structural abnormalities are characteristic of the Bardet-Biedl syndrome, and are still best imaged by urography.

The pituitary gland in the Laurence-Moon syndrome.

The apparent hypogonadism in patients with the Laurence-Moon syndrome has been variably attributed to unresponsiveness of target organs to gonadal hormones, primary end-organ failure, hypothalamic dysfunction, or pituitary failure. We report the first immunocytologic study of the pituitary gland in this rare disorder. No morphologic abnormalities were noted. The numbers and immunoreactivities of adenohypophyseal cell types were normal. No microscopic abnormalities were evident in the hypothalamus and target organs. The results of our study are consistent with recent biochemical data that suggest that pituitary function is normal in patients with this syndrome.

Visual function in Laurence-Moon-Bardet-Biedl syndrome. A survey of 26 cases.

In 1984, 32 persons with Laurence-Moon-Bardet-Biedl syndrome (LMBB syndrome) were registered in Norway. Of these, 26 stayed for 10 days at the Frambu Health Centre, where they consulted a pediatrician, a psychologist, a dentist, a social worker, a geneticist, a teacher for the blind and an ophthalmologist. The ocular examination showed the eye disease in cases of LMBB syndrome to be homogeneous and fulminant tapetoretinal degeneration of the retinitis pigmentosa type.

[Glomerular nephropathy in the Bardet-Biedl syndrome]. / La néphropathie glomérulaire du syndrome de Bardet-Biedl.

A case of Bardet-Biedl syndrome (BBS) with kidney involvement and renal failure is reported. Light microscopy demonstrates fibrosis of 40% of glomeruli, altered tubules and interstitial fibrosis; no cystic formation is present and immunofluorescence studies are negative. In electron microscopy, the glomerular basement membrane (GBM) looks twisted and uniformly thickened with segmental effacement of the trilaminar architecture; fibrillary material is accumulated close to the inner layer of the GBM. Intermittent peritoneal dialysis is initiated 2 years later; death occurs, after one year of dialysis, due to a bleeding duodenal ulcer. Chronic renal failure seems to be the most frequent cause of death in BBS and several mechanisms are involved. Tubulo-interstitial lesions and renal cysts have been well documented. Glomerular damage with early ultrastructural changes of the GBM may be implicated in the occurrence of renal failure. Further studies are needed to define the incidence and the specificity of the GBM abnormalities in BBS.

Retinal and neurologic findings in the Laurence-Moon-Bardet-Biedl phenotype.

The nosology of the Laurence-Moon and Bardet-Biedl syndromes has been controversial. Presented is a patient with polydactyly, retinopathy, ataxia, low-average intellectual function, and obesity. These features constitute a composite of both syndromes and reflect the clinical heterogeneity that may be seen. Accordingly, the authors suggest the use of the term "Laurence-Moon-Bardet-Biedl phenotype" until these syndromes can be defined in some other manner. The neuroradiologic studies document atrophy of the cerebellum that accounts for the ataxia. Electroretinograms (ERG) demonstrate the decline in retinal function over a 16-year interval and the delayed cone ERG b-wave implicit time with normal cone amplitudes to 30 Hz white flicker that can exist in the early stage of this disorder.