Delayed diagnosis of Townes-Brocks syndrome with multicystic kidneys and renal failure caused by a novel SALL1 nonsense mutation: A case report

Abstract

Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital anomaly syndrome characterized by the triad of anorectal, hand and external ear malformations. Kidney involvement is less common and may progress to end-stage renal failure (ESRF) early in life. The present study reports the case of a male patient presenting with multiple bilateral cortical kidney cysts at the age of 4 years, at which time the kidneys were of normal size and function. A clinical diagnosis of autosomal recessive polycystic kidney disease was made initially as the patient's parents are clinically healthy. However, the consideration of extra-renal involvements (imperforate anus at birth, preaxial polydactyly and dysplastic right ear) following the progression of the patient to ESRF at the age of 16 years, led to the diagnosis of TBS. This prompted sequencing of the SALL1 gene, which identified a novel heterozygous nonsense mutation in the mutational ‘hotspot’ of exon 2 (c.874C>T, p.Q292X), and this mutation was not detected in healthy controls. The current case highlights that TBS may present with normal sized, cystic kidneys in childhood, while recognition of extra-renal features of cystic kidney diseases, such as TBS, and genetic testing may facilitate the correct diagnosis and transmission mode. Reaching a correct diagnosis of as TBS is important since this condition has a 50% rate of transmission to offspring and can progress to ESRF early in life.

A Genotyped Case of Townes–Brocks Syndrome with Absent Pulmonary Valve Syndrome from Turkey

“…Genitourinary anomalies such as renal agenesis, renal hypoplasia, polycystic kidneys, dysplastic kidneys, posterior urethral valves, vesicoureteral reflux, and meatal stenosis may be observed in patients with TBS, as well as functional impairment of kidney with or without structural abnormalities (42% of individuals). 4,10,11 In the present case, we detected increased renal parenchymal echogenicity and mildly pelvicalyceal dilatation in both the kidneys. Transient renal functional impairment occurred within the first 4 days of life.…”

“…Respiratory support may be administered for pulmonary impairment caused by heart defects. 3,[8][9][10][11]…”

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

“…Bilateral small kidneys were also described in 2 other cases with TBS diagnosed at 16 and 19 years old (Engels et al, 2000; Lin et al, 2016). For both, kidney disease was known since infancy, with ERSD at 16 years old for one of them.…”

“…In 1997, Newman first drew attention to symptomatic renal failure in TBS case (Newman, Brunet, & Donnai, 1997). Seventy‐nine pediatric cases of TBS with genetic confirmation are described in the literature (Bardakjian, Schneider, Ng, Johnston, & Biesecker, 2009; Barry & Reddy, 2008; Botzenhart et al, 2005, 2007; Choi et al, 2010; Engels et al, 2000; Keegan et al, 2001; Kohlhase et al, 1998, 2003; Kosaki et al, 2007; Lawrence et al, 2013; Liang, Shen, & Cai, 2008; Liberalesso et al, 2017; Lin et al, 2016; Miller et al, 2012; Morisada et al, 2014; Rodríguez Asensio et al, 2003; Salerno, Kohlhase, & Kaplan, 2000; Stevens & May, 2016; Stoll, Alembik, Dott, & Roth, 2010; Sudo et al, 2010; Valikodath et al, 2020; van Bever et al, 2009; van den Akker, van de Graaf, Dooijes, & van Essen, 2009; van den Hondel et al, 2016; Walter et al, 2006; Weber et al, 2006), including 34 cases with morphological and/or functional renal impairment, that is, 43% (Botzenhart et al, 2005, 2007; Engels et al, 2000; Keegan et al, 2001; Lawrence et al, 2013; Lin et al, 2016; Morisada et al, 2014; Stevens & May, 2016; Sudo et al, 2010; van Bever et al, 2009; van den Akker et al, 2009; van den Hondel et al, 2016; Walter et al, 2006; Weber et al, 2006).…”

“…A review of reported cases aged at least 18 years old at diagnosis time of TBS, with renal impairment is detailed in Table 1 (Eker & Balasar, 2015;Faguer et al, 2009; Reardon et al, 2007). Adult cases without specified age of renal failure were excluded (Barakat, Butler, Salter, & Fogo, 1988; Botzenhart et al, 2005; de Vries‐Van der Weerd, Willems, Mandema, & ten Kate, 1988; Eker & Balasar, 2015; Engels et al, 2000; Lin et al, 2016; Newman et al, 1997; Sudo et al, 2010; Unuigbe, Azubike, Okaka, Osarenkhoe, & Onuora, 2007).…”