Congenital nephrotic syndrome and diffuse mesangial sclerosis in siblings

This is a rare renal disease characterised by steroidresistant nephrotic syndrome in the first years of life with rapid progression to end-stage renal failure. Its occurrence is usually sporadic, and it has been associated with a mutation in the Wilms tumour (WT1) suppressor gene. Recently new gene defects causing isolated diffuse mesangial sclerosis, such as LAMB2 and PLCE1 mutations, have been described. We describe the case of an infant with congenital nephrotic syndrome, whose renal biopsy revealed the presence of diffuse mesangial sclerosis. The parents were consanguineous and reported the death of a son at the age of six months with the same diagnosis. A search for mutations in exons 7, 8, 9 and 10 and surrounding regions of WT1 gene was negative. We describe the clinical and pathological features of this rare condition and discuss the known gene mutations associated with familial forms of it. Key-Words: Congenital nephrotic syndrome; family diffuse mesangial sclerosis; genetic defect; infant. INTRODUCTION Diffuse mesangial sclerosis (DMS) is the second most frequent cause of primary congenital nephrotic syndrome. Initially described in its sporadic form, it was later associated with autosomal recessive inheritance occurring occasionally in siblings and monozygotic twins and in the presence of parental consanguinity1 -3. The clinical picture is characterised by the presence of oedema and proteinuria usually appearing in the second or third year of life. However, it may also appear in the first three months of life, and be classified as congenital nephrotic syndrome. Evolution to end -stage renal failure (ESRF) is frequent, and renal transplantation is the only effective treatment as there are no reports of recurrence in the graft3. In this case report, the development of nephrotic syndrome at the age of three months, the existence of DMS, the family background and laboratory exams suggest a rare case of familial isolated diffuse mesangial sclerosis, probably associated with an autosomal recessive gene not yet identified. Congenital nephrotic syndrome and diffuse mesangial sclerosis in siblings Isabel Carvalho1, Graça Ferreira1, Eduarda Marques1, Mercedes Sanchez2, Rosete Nogueira2, Maria S. Faria3, Conceição Mota3 1 Paediatrics Unit. Vila Nova de Gaia Hospital. Gaia, Portugal. 2 Anatomical Pathology Unit. Vila Nova de Gaia Hospital. Gaia, Portugal. 3 Paediatric Nephrology Unit. Maria Pia Hospital. Oporto, Portugal. Received for publication: 13/05/2010 Accepted in revised form: 10/08/2010 CASE REPORT Port J Nephrol Hypert 2010; 24(4): 305-308 Advance Access publication 14 September 2010 Nefro 24-4 MIOLO OK.indd Sec1:305 15-11-2010 10:17:22 306 Port J Nephrol Hypert 2010; 24(4): 305-308 CMYKP Isabel Carvalho, Graça Ferreira, Eduarda Marques, Mercedes Sanchez, Rosete Nogueira, Maria S. Faria, Conceição Mota