Townes-Brocks Syndrome 2

A number sign (#) is used with this entry because of evidence that Townes-Brocks syndrome-2 (TBS2) is caused by heterozygous mutation in the DACT1 gene (607861) on chromosome 14q23. One such family has been reported.

For a discussion of genetic heterogeneity of Townes-Brocks syndrome, see TBS1 (107480).

Clinical Features

Webb et al. (2017) studied a family in which 6 members exhibited features overlapping those of Townes-Brocks syndrome. The proband was a 20-month-old girl who was born with imperforate anus, rectovaginal fistula, crossed fused renal ectopia, and vesicoureteral reflux. In addition, her right ear was smaller than the left, and both ears showed overfolding of the superior helix and cupping, which was more pronounced on the right. Her 7-year-old brother also exhibited imperforate anus, as well as hypospadias, crossed fused renal ectopia, vesicoureteral reflux, and overfolding of both ears that was more pronounced on the right and also involved cupping on the right. Their mother had bilateral ear cupping, and spina bifida occulta had been diagnosed in her teen years. The mother's half-sister had severe microtia of the left ear, as did the proband's maternal grandmother, who also had bifid uterus.

Molecular Genetics

By whole-exome sequencing in a 3-generation family segregating features of Townes-Brocks syndrome, negative for mutation in the SALL1 gene (602218), Webb et al. (2017) identified heterozygosity for a nonsense mutation in the DACT1 gene (W419X; 607861.0001) that segregated fully with disease and was not found in public variant databases. The authors noted that identification of additional affected individuals with DACT1 mutations was necessary to understand the full spectrum of disease.