Focal Sclerosing Glomerulonephritis in a Child with Laurence-Moon-Biedl Syndrome

Abstract

We report a 6-year-old white male with Laurence-Moon-Biedl syndrome and focal sclerosing glomerulonephritis (FSGN). To our knowledge, FSGN has not been reported previously in patients with this syndrome. We wish to alert the clinician to the wide variety of renal abnormalities that can be seen in patients with this rare, autosomal recessive disorder.

Introduction

Laurence and Moon [ 1 ] described a syndrome in 1866 characterized by retinitis pigmentosa, mental retardation, obesity, short stature and hypogonadism. Bardet [2] and Biedl [3] added polydactyly, anal atresia, skull deformities and gastrointestinal abnormalities to the spectrum of clinical findings.

Herein, we report a 6-year-old white male with Laurence-Moon-Biedl syndrome who had a previously undescribed renal abnormality. We wish to alert the clinician to the wide variety of kidney abnormalities in patients with this rare syndrome.

Case Report

The patient was a white male bom at 32 weeks gestation to a 16-year-old gravida 1, para 0, single mother. He was born vaginally without complications. His birth weight was 1,870 g (30th centile). His birth length and head circumference were within normal range for gestational age. Excluding prematurity, the pregnancy and family histories were unremarkable. Consanguinity was denied. During the neonatal period. Cyanosis as well as a postaxial skin tag on his right hand were noted (fig. 1a, b). An endocardial cushion defect, situs inversus and an absent spleen were identified. Chromosome studies were normal. He underwent a right Blalock-Taussig shunt operation at 11 months of age and initially did well. At the age of 3, psychomotor developmental delay was noted and he became markedly obese. A small penis and small bilaterally descended testicles were noted. He was diagnosed to have Laurence-Moon-Biedl syndrome, although there were not retinal abnormalities. At 6 years of age, he again became cyanotic and presented with nephrotic syndrome. His weight was then 45 kg (> 95th centile) and the height was 124.5 cm (95th centile). His cardiac findings were then interpreted as tetralogy of Fallot with an atrial ventricular canal defect and dextrocardia. Creatinine clearance was 67 ml/ min/1.73m². Percutaneous renal biopsy was performed. It contained 36 glomeruli, all of which appeared hypertrophic, possibly related to the cyanotic heart disease, and showed mild mesangial hypercellularity. One glomerulus was hyalinized and another showed segmental sclerosis (fig. 1c). No tubular atrophy or vascular lesions were noted. Staining with antisera for IgG, IgM, IgA, C3 and C4 was negative. Electron microscopy demonstrated segmental foot process fusion with microvillus transformation and no deposits. There was also a slight mesangial prominence. These findings were consistent with the diagnosis of early focal sclerosing glomerulonephritis (FSGN).

Fig. 1.

Facial (a) and hand (b) photographs of the patient at 6 years of age. Note the round face, obesity and polydactyly. c Renal histology - glomerulus demonstrating early segmental sclerosis. PAS. × 450.

Discussion

Laurence-Moon-Biedl syndrome is characterized by obesity (83% of cases), mental retardation (80%), polydactyly (75%), retinitis pigmentosa (68%) and hypogenitalism/hypogonadism (60%) [4], Other features such as cardiac defects, strabismus, fifth finger clinodactyly, urologic anomalies, hirsutism and short stature may also be present.

Renal involvement may occur in the majority of patients and is an important factor in the cause of death. Renal findings are now considered a cardinal feature of this autosomal recessive syndrome and include: variation in kidney size, hydronephrosis, blunted calyces, parenchymal damage, pyelonephritis, atrophic tubules, chronic glomerulonephritis, cystic changes, renal hypoplasia and dysplasia, vesicoureteral reflux, mesangial proliferation and sclerosis, interstitial fibrosis and tubulointerstitial disease [5–11]. To our knowledge, FSGN has not been reported previously in these patients and should be added to the list of renal abnormalities seen in this syndrome.

The incidence of renal disease in this syndrome generally ranges from 70 to 90%, and uremia may be the leading cause of death in 30–50% of patients [10, 12]. Other reports record the incidence of obvious renal disease to be less. For example, Harnett et al. [10] described recently the nature, extent and severity of renal involvement in 20 patients with this syndrome and found that one half of the patients had hypertension; 3 had end stage disease; 14/17 lacked urine-concentrating ability; 18/19 had calyceal clubbing, cysts or diverticulae and 17/19 had fetal lobulations of the kidneys. Only 3 (15%) of their 20 patients had marked renal impairment, although they did not perform histologic studies.

In summary there is a wide array of renal anomalies seen in patients with this rare, autosomal recessive syndrome. Because renal disease may be found in more than 70% of patients, and is an important factor in the cause of death, it should be looked for in every patient with this syndrome. Patients who have significant proteinuria, nephrotic syndrome or reduced renal function should undergo a renal biopsy to better characterize and understand the degree of renal involvement in the patient and to offer the appropriate medical treatment.