Adult diagnosis of Townes–Brocks syndrome with renal failure: Two related cases and review of literature

Abstract

Townes–Brocks syndrome (TBS) is a rare autosomal dominant syndrome, resulting from heterozygous variant in SALL1 gene and initially characterized by the triad of anorectal, thumb, and ear malformations. Essentially described in children, adult case reports are uncommon. Renal involvement has already been reported in adults and children but poorly described. Structural abnormalities such as hypodysplasia, unilateral renal agenesis or multicystic kidneys have been described, as well as functional impairment (with or without structural abnormalities) that may progress to end‐stage renal disease (ESRD). We report two adult cases (mother and daughter) which exhibited kidney hypoplasia (focal and segmental glomerulosclerosis for the mother) and ESRD. The mother had unilateral polydactyly. TBS was suggested after physical examination. TBS diagnosis was confirmed by identification of a SALL1 variant. We conducted a literature review to evaluate the renal anomalies in TBS cases diagnosed in adulthood. Among 44 adult cases of TBS with genetic confirmation (including our two cases), 10 had kidney disease. The circumstances of renal failure diagnosis were incidental findings (2/5), gout (2/5), or repeated episodes of pyelonephritis (1/5). The median age of kidney disease diagnosis was 30 years old and of renal transplant 49 years old. The most frequent renal malformation was bilateral kidney hypoplasia. TBS is probably underestimated in adulthood and this report highlights that less obvious elements of morphology such as dysplasic ears can facilitate the diagnosis of TBS. As long‐term prognosis of renal involvement in TBS patients remains largely unknown, a regular evaluation is required throughout life for patients.

Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review

“…28% of the patients had serum creatinine levels above the normal range but did not meet the diagnosis of renal failure, hence, were considered having renal injury. Five patients underwent successful kidney transplants and two of them developed graft rejection [ 11 – 14 ]. The patients were grouped based on the location of the SALL1 mutations they carried (Fig.…”

Townes–Brocks syndrome with adult renal impairment in a Chinese family: A case report

“…It has been reported that renal anomalies, including functional impairment with or without structural abnormalities, were detected in 43% of patients with TBS. Recently, Beaudoux et al [ 3 ] reported two related TBS cases that exhibited kidney hypoplasia (focal and segmental glomerulosclerosis) and ESRD. Their literature review showed that 10 of 44 adult cases of TBS with genetic confirmation had kidney disease.…”

“…This syndrome is an autosomal dominant syndrome caused by a pathogenic variant of SALL1 gene[ 1 ]. This syndrome was first described by Townes and Brocks in 1972, and the mutations in SALL1 responsible for TBS were first identified by Kohlhase in 1998[ 2 , 3 ]. Thereafter, many TBS cases were found with pathogenic variants of SALL1 to make a molecular diagnosis.…”

Novel mutation in the SALL1 gene in a four-generation Chinese family with uraemia: A case report

“…Almost half of the individuals had varying degrees of renal impairment, and 22% of the individuals progressed to renal failure. Some of the patients successfully underwent kidney transplantation, and two of them experienced graft rejection[ 3 , 7 , 9 , 10 ].…”