Unbalanced 4;6 translocation and progressive renal disease

Abstract

Two sibs are described with an unbalanced 4;6 translocation resulting in partial trisomy 6p and monosomy for distal 4p. Growth retardation, psychomotor retardation, and characteristic facial appearance are present. The facial anomalies include high prominent forehead, blepharoptosis, blepharophimosis, high nasal bridge, bulbous nose, long philtrum, small mouth with thin lips, and low-set ears. Both children have small kidneys and have had proteinuria since early childhood. The older boy developed progressive renal disease including hypertension and renal failure necessitating renal transplantation at age 18 years. Renal biopsy of the younger girl also indicates significant renal involvement. Progressive renal disease is likely an important part of the trisomy 6p phenotype.

Renal complications in 6p duplication syndrome: Microarray‐based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS)

“…FSGS, observed in the younger sibling reported by Pierpont et al [] (Patient 8 in Table ) and the present patient, would not be of coincidental occurrence but a consequence of 6p duplication. Some of previously reported patients with 6p duplication syndrome manifesting proteinuria at the time of publication might have developed FSGS, if they had renal biopsy.…”

“…Detailed information about renal complications has been sparse. Pierpont et al [] reported two siblings with unbalanced translocations with the breakpoints of 4p and 6p, resulting in a distal 6p duplication and a distal 4p deletion. The older sibling (Patient 7 in Table ), born at term weighing 2.6 kg, showed proteinuria at age 2 years, when a right ectopic kidney, a left hypoplastic kidney, and bilateral grade III vesicoureteral reflux were also observed.…”

“…Some of previously reported patients with 6p duplication syndrome manifesting proteinuria at the time of publication might have developed FSGS, if they had renal biopsy. Pierpont et al [] stressed importance of renal biopsy in all patients with this syndrome manifesting abnormal renal findings to clarify the underlying pathology. Mesangial deposits observed in the younger sibling [Pierpont et al, ] might support a non‐specific immune complex glomerulonephritis with significant glomerulosclerosis as the etiology of her FSGS.…”

“…Pierpont et al [] stressed importance of renal biopsy in all patients with this syndrome manifesting abnormal renal findings to clarify the underlying pathology. Mesangial deposits observed in the younger sibling [Pierpont et al, ] might support a non‐specific immune complex glomerulonephritis with significant glomerulosclerosis as the etiology of her FSGS. However, successful renal transplantation in the present patient suggested a primary renal problem not a systemic abnormality as the cause of her FSGS resulting in end‐stage renal failure.…”

“…The translocation breakpoints of 6p vary from 6p11 to 6p25 [Wauters et al, ]. Renal complications occur frequently in the syndrome, including proteinuria, hypoplastic/aplastic kidney, and hydronephrosis (Table ); therefore gene(s) in the common duplicated region of 6p have been postulated to play a role in renal development and function [Pierpont et al, ]. However, no studies have uncovered candidate genes because all previously reported patients with 6p duplication and renal complications were analyzed by conventional G‐banded karyotyping [Pierpont et al, ] or by fluorescent in situ hybridization (FISH) [Giardino et al, ; Stohler et al, ].…”