Variable expressivity of renal involvement in a further family with Townes–Brocks syndrome

Abstract

List of key featuresTriphalangeal thumb Bifid thumb Dysplastic ears with over-folded helix Hearing loss Imperforate anus Renal hypoplasia/agenesis Clinical summaryA 3-year 4-month-old boy was referred to the genetic clinic with dysplastic ears, thumb anomaly, and developmental delay. He was delivered at 30 weeks of gestation by Cesarean section. His birth weight was 1320 g (25th centile), length 43 cm (∼50th centile). He was operated on for an imperforate anus on the first day of his life. Examination in the genetic clinic indicated a weight of 10 kg (less than third centile), occipital-frontal circumference of 45 cm (less than third centile), dysplastic ears with hypoplastic ear lobules, bilateral triphalangeal thumbs together with a bifid thumb on the right, spasticity and flexion contractures in his lower extremities, flat feet, and overlapping toes (Fig. 1). He had moderate hearing loss and chronic renal failure. He had mental retardation. Urinary system ultrasonography showed bilateral small kidneys with grade-2 parenchymal echogenicity. Intraparenchymal hemorrhage was detected on cranial ultrasonography, and it was subsequently confirmed by MRI. Echocardiography was normal. Radiography of the hands indicated bilateral triphalangeal thumbs with a rudimentary middle phalanx on the left and a double distal phalanx on the right. He was the first child of a G2P1 29-year-old mother and a nonconsanguineous 31-year-old father. His mother was hospitalized repeatedly in pregnancy because of increased urea, creatinine levels, and hypertension. On physical examination, she also had bilateral dysplastic ears with over-folded helices, bilateral triphalangeal thumbs together with loss of flexion on the second interphalangeal joints, and a medial deviation of the distal phalanges (Fig. 1). Renal scintigraphy showed renal agenesis on the left and grade-2 parenchymal echogenicity on the right. She was diagnosed with chronic renal failure and hypertension. In addition, she had mild hearing loss. She had undergone anorectal repair for an imperforate anus as a neonate and several preauricular skin tags had been removed in childhood. Neither the mother nor the child had any cardiac or spinal abnormalities. Both had normal karyotypes. Molecular studies were not possible, but on the basis of these clinical findings, we diagnosed Townes-Brocks syndrome (TBS).

A mouse model of Townes-Brocks syndrome expressing a truncated mutant Sall1 protein is protected from acute kidney injury

“…Moreover, the degree of reduced kidney weight adjusted for body weight (15% for Sall1 TBS vs. 31% for Sall1 cKO ) also correlated with the severity of CKD in these two different Sall1 mutant alleles, as assessed by sCr. A significant proportion of patients with TBS due to dominant mutations in SALL1 develop CKD, with progression to end-stage kidney disease (9,32,39). Based on these observations, we conclude that congenitally reduced nephron number contributes to reduced glo- merular filtration in adult Sall1 mutant mice.…”

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

“…TBS has a prevalence of 1 in 250,000 individuals in the general population ( 12 ). It is a rare autosomal dominant malformation syndrome characterized by the core triad of anorectal malformation (imperforate anus, anteriorly-placed anus and anal stenosis), hand malformations (pre-axial polydactyly, triphalangeal thumbs and bifid thumb) and external ear malformation (preauricular ear tags and overfolding of ear helices) associated with deafness ( 13 ).…”

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

“…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).…”