title: Delayed diagnosis of Townes-Brocks syndrome with multicystic kidneys and renal failure caused by a novelSALL1nonsense 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.
authors.affiliation: Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Lin
authors.affiliation: Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: UCL Centre for Nephrology, Royal Free Campus, UCL Medical School, University College London, London NW3 2PF, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gale
authors.affiliation: Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Medical Ultrasound, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors.forename: Ren
authors.initials: R
authors.lastname: Zou
authors.affiliation: Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Bian
authors.affiliation: Department of Nephrology, XinHua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.
authors.forename: Geng-Ru
authors.initials: GR
authors.lastname: Jiang
keywords: SALL1; Townes-Brocks syndrome; multicystic kidneys; novel mutation; renal failure