Structural Heart Defects And Renal Anomalies Syndrome

A number sign (#) is used with this entry because of evidence that structural heart defects and renal anomalies syndrome (SHDRA) is caused by homozygous mutation in the TMEM260 gene (617449) on chromosome 14q22.

Clinical Features

Ta-Shma et al. (2017) studied 3 affected sibs from a consanguineous Ashkenazi Jewish family, 2 of whom died in the first few months of life, as well as a similarly affected girl born of double-first-cousin Arab parents, who died suddenly at 1 year of age. All 4 children exhibited complex congenital heart defects, including atrial and ventricular septal defects (ASDs and VSDs), tricuspid valve atresia, truncus arteriosus, tetralogy of Fallot, interrupted aortic arch, right aortic arch, persistent left superior vena cava, and partial anomalous pulmonary venous return. In addition, all had elevated creatinine levels, 3 showed generalized edema, and 2 of the Ashkenazi Jewish sibs developed renal failure with oliguria and anuria, before succumbing to multiorgan failure and cardiac and pulmonary failure, respectively. Neurologic defects included partial agenesis of the corpus callosum in the deceased brother and sister, and microcephaly in the Arab girl. The surviving 2-year-old Ashkenazi Jewish boy had 3 muscular VSDs that closed spontaneously, a small ASD, and multiple small left renal cysts. The Arab girl had an older sister who died at 35 days of life as a result of congenital heart disease.

Inheritance

The transmission pattern of structural heart defects and renal anomalies syndrome in the families reported by Ta-Shma et al. (2017) was consistent with autosomal recessive inheritance.

Molecular Genetics

By whole-exome sequencing in 2 unrelated families with structural heart defects and renal anomalies syndrome, Ta-Shma et al. (2017) identified homozygosity for 2 different mutations in the TMEM260 gene (617449.0001 and 617449.0002) that segregated with disease.