Table 1 Clinical phenotype of probands with disease-causative SMAD6 variants.

Tan et al.¹⁰

Cardiovascular malformations

Bicuspid aortic valve (LVO)

1

NS

1.5 y^a

Aortic stenosis

Cardiovascular malformations

Bicuspid aortic valve with coarctation of the aorta (LVO)

1

NS

30 y^a

Aortic stenosis

Timberlake et al.¹¹; Timberlake et al.¹²

Craniosynostosis

Craniosynostosis

17

NS

Paediatric^b

Metopic synostosis (N = 12), sagittal synostosis (N = 3), metopic + sagittal synostosis (N = 2)

Jin et al.⁵

Congenital heart defect

Tetralogy of Fallot (CTD)

3

Unknown^c

Paediatric^b

Pulmonary stenosis (subvalvular (N = 2), valvar (N = 1)), ventricular septal defect (malalignment) (N = 1), coronary artery anomaly (right) (N = 1), left aortic arch with normal branching pattern (N = 1), patent foramen ovale (N = 1)

Congenital heart defect

Transposition of the Great Arteries (CTD)

1

Unknown^c

Paediatric^b

Atypical coronary arteries in D-loop Transposition of the Great Arteries, transposition D-loop of the Great Arteries with intact ventricular septum, left aortic arch with a normal branching pattern

Congenital heart defect

Hypoplastic left heart syndrome (LVO)

1

Unknown^c

Paediatric^b

Aortic arch hypoplasia, aortic atresia, hypoplasia ascending aorta, hypoplastic left ventricle (subnormal cavity volume), mitral atresia, restrictive patent foramen ovale

Congenital heart defect

Coarctation of the aorta (LVO)

1

Unknown^c

Paediatric^b

Atrial septal defect (secundum), left-sided patent ductus arteriosus, tubular hypoplasia of aorta, ventricular septal defect (malalignment, muscular outlet)

Congenital heart defect

Bicuspid aortic valve with coarctation of the aorta (LVO)

1

Unknown^c

Paediatric^b

Aortic arch hypoplasia, hypoplastic left ventricle (subnormal cavity volume), patent foramen ovale

Congenital heart defect

Other

1

Unknown^c

Paediatric^b

Left aortic arch with normal branching pattern, partially anomalous pulmonary veins, sinus venosus septal defect (superior type)

Congenital heart defect

Other

1

Unknown^c

Paediatric^b

Vascular ring, aberrant left subclavian artery, abnormal branching right aortic arch, right aortic arch left ligament

Gillis et al.⁴; Luyckx et al.⁷; Park et al.⁸

Cardiovascular malformations

Bicuspid aortic valve-related thoracic aortic aneurysm

15

NS

Average 64.1 y

Aortic valve calcification (N = 1), coarctation of the aorta (N = 2), aortic regurgitation (N = 1), aortic stenosis (N = 1)

Kloth et al.^6d

Cardiovascular malformations

Coarctation of the aorta (LVO)

1

S^e

6 y

Suspected tricuspid aortic valve

Other

1

NS

10 y

Dysplastic and stenotic pulmonary valve, dilated cardiomyopathy, stenotic left main coronary artery

Yang et al.¹³; Shen et al.⁹

Radioulnar synostosis

Radioulnar synostosis

77

NS

Average 5 y

Lateral left radioulnar synostosis (N = 17), lateral right radioulnar synostosis (N = 6), bilateral radioulnar synostosis (N = 54)

Calpena et al.³

Craniosynostosis

Craniosynostosis

26

S^f/NS^g

Not reported

Metopic synostosis (N = 15), sagittal synostosis (N = 6), right coronal synostosis (N = 2), sagittal + left coronal synostosis (N = 1), sagittal + bicoronal synostosis (N = 2)