Table I:
Patients with Dilated Thoracic Aorta or Thoracic Aortic Aneurysm (n=21/114, M=6, F=15):
| Study ID | Sex (Age) | FLNA mutation | Aneurysm Location | Other significant cardiopulmonary or medical findings | Cardiovascular Outcome |
|---|---|---|---|---|---|
| Boston Cohort #9 | F (43y) | GT to GC at exon 4+2 | - Preop: Sinus of Valsalva aneurysm involving the non-coronary sinus (4.0×3.5 cm), eroding down toward the roof of the LA - Dilated thoracic aorta (5.1cm) from the sinuses to the mid-transverse aorta (between the left common carotid and the left subclavian artery) |
- Congenital bicuspid aortic valve with moderate aortic stenosis with mild AR prior to Ross - Seizures, prolactin-secreting adenoma |
1) S/p Dacron interposition graft in ascending aorta at age 36; S/p Ross procedure for aortic stenosis 2) Aortic arch began to dilate at age 40 years |
| Boston cohort #27 | F (16y) | c.4147 del G single base pair deletion exon 25, p.(Ala1383Leufs*10) | -Thoracic ascending aorta (unknown) | - Hyperflexibility and joint dislocations - No seizures |
n/a |
| Boston Cohort #29 | F (15y) | c.116 C>G exon 2 p.(Ala39Gly) | - Sinus of Valsalva aneurysm | - Hyperelasticity of the large vessels, hyperextensibility of skin, joint laxity and subluxations - Seizures, mild developmental delay |
n/a |
| Boston Cohort #36 | F (41y) | G>A intron 2 | - Sinuses of Valsalva aneurysm (non-coronary and right-coronary sinuses) - Mildly dilated thoracic ascending aorta |
- Dysplastic AV, perimembranous VSD, moderate AR, mild MR. Normal abdominal aorta - Hyperflexible with joint dislocations - Seizures |
1) Progressive increase in aortic size from age 29 to 41 years 2) Died age 41yrs of lethal aortic rupture, at an aortic root size of 4.2 cm |
| Boston Cohort #37 | F (17y) | C>T exon 48, p.(Gln2385*) | - Dilated aortic root (4.8cm) - Dilated thoracic ascending aorta (2.7cm) |
- PDA, PFO, perimembranous VSD, MVP. Pulmonary arterial dilation (3.7cm). Coronary fistula to proximal coronary artery - Developmental delay, no documented seizures |
1) s/p PDA repair neonatal period 2) s/p Bilateral lung transplant during infancy 3) s/p Aortic root and valve replacement at age 13 years 4) s/p mitral valve annuloplasty ring and mitral valve repair |
| Boston Cohort #39 | M (36y) | c.6915bp C>G exon 41, p.(Tyr2305*) | - Dilated thoracic ascending aorta | - AR - Seizures |
1) Died age 36 yrs from aortic rupture and cardiac tamponade |
| Reinstein 2013, F3 ++ Boston Cohort #85 |
F(11y) | c.2193C>A exon15, p.(Tyr731*) | - Sinus of Valsalva aneurysm involving the non-coronary cusp. - Mildly dilated thoracic ascending aorta - Mildly dilated descending aorta. |
- PDA, perimembranous VSD; dysplastic pulmonary, tricuspid and aortic valves. Moderate AR, PFO - Pulmonary hypertension with lung disease at birth that later stabilized. Dilatation of main pulmonary artery and its branches. Dilated head and neck branches. Hyperflexible. - No seizures |
1) PDA ligated at 10 weeks 2) Development of sinus of Valsalva aneurysm by age 6 2) Aortic root Z score normal at birth and increased to 5 by age 11 |
| Boston Cohort #107 | F(1Y) | Complete deletion | - Nl size aortic root - Dilated thoracic ascending aorta (z score=4.6) |
- Small PDA - Hyperflexible, no seizures |
No cardiac symptoms |
| Boston Cohort #114 | F(21) | c.62_64TCG exon 2,p.(Val21dup) | - Sinus of Valsalva aneurysm involving the right and non-coronary cusps - Mildly dilated thoracic ascending aorta |
- PDA, perimembranous VSD, MVP with mild mitral regurgitation - Asthma, normal intellect, no seizures |
1) PDA ligated at 10 months |
| Guerrini 2004, 3-II:1 | M (49y) | A>G at intron 11 | -Thoracic ascending aorta | - Dysplastic AV - Bifid epiglottis, seizures |
1) s/p aortic valve replacement and ascending aorta replacement at age 26 yrs |
| Sole* 2009, F8 | F(43y) | c.365 T>G exon 2 p.(Val122Gly) Mother of Sole F9. |
- Aortic aneurysm (no further detail) | - Joint hypermobility - Seizures |
1) s/p Aortic aneurysm surgery at age 38yrs |
| Sole* 2009, F9 | F(15y) | c.365T>G exon 2 p.(Val122Gly) | - Aortic aneurysm (no further detail) | - EDS with ankle dislocation and joint hyperlaxity - No Sz |
Treated with beta-blockers |
| Sole** 2009,F15 | F(35y) | c.356T>A exon 2 p.(Val122Gly) | - Aortic aneurysm (no further detail) | - EDS- with joint hyperlaxity, AR - Seizures |
Treated with beta-blockers |
| Fergelot** 2012, P1 | M(57y) | c.356T>A exon 2, p.(Val122Gly) Father of Sole 2009, F15 |
- Severely dilated aortic root by age 41 years - Dilated thoracic ascending aorta (6cm) |
- Severe AR, thrombocytopenia - Normal cognitive development, no seizures |
1) s/p Aortic root repair and also AV replacement at age 41 yrs 2) s/p Bentall at age 57 yrs for progressive dilatation of the ascending aorta and also stenosed aortic valve prosthesis 3) Died post- Bentall of severe bleeding complications at age 57 |
| de Wit 2011, P5 | F(42y) | c.6635delTCAG exon 41, p.(Ser2213*) | -Dilated ascending aorta | - Severe AR from dysplastic AV, VSD - No seizures |
1) s/p VSD repair and aortic valve replacement at age 24 yrs 2) s/p Bentall at age 36 yrs |
| Masurel-Paulet 2010, P1 | M(6y) | c.994delG exon 7 p.(Lys331*) | - Sinus of Valsalva aneurysm | - PDA. AR, enlarged RV with wall hypertrophy. Pan-pulmonary emphysema and pulmonary arterial hypertension - Developmental delay, poor feeding, no seizures |
s/p PDA ligation after 5 days of life |
| Reinstein 2013, F1 | F(38y) | c883-880 del8 exon 6, p.(Asn296Glu fs*38) | - Sinus of Valsalva aneurysm | - Diffuse ectasia of aortic branch vessels - No seizures |
s/p valve-sparing aortic root repair by age 38 years Root increased from 48mm to 57 cm (preop) |
| Reinstein 2013, F5 | F(23y) | c.7813delC exon 48, p.(Leu2605Trpfs*2) | - Dilated aortic root (4.5cm) - Dilated thoracic ascending aorta |
- AR, Pulmonary artery dilatation - Seizures |
n/a |
| Reinstein 2013, M2 | M(2mo) | c.5498-5504delCACCACinsAC exon 34, p.(Ala1833Aspfs*13) | - Dilated thoracic aorta - Dilated abdominal aorta - Elongated/tortuous supra-aortic vessels |
- PDA. Dysplastic AV, thickened mitral and tricuspid valves on autopsy, ASD, VSD - Pulmonary hypertension, with pulmonary artery dilatation progressive heart failure. - No seizures |
Died at age 2 months, secondary to sepsis following pulmonary hypertension and heart failure |
| Reinstein 2013, M3 | M(15y) | c.381G>C exon3, p.(Lys127Asn) | - Dilated aortic root (3.1cm, nl < 2.8cm) | - MVP, history of pneumothorax, slightly hyperextensible skin, joint hypermobility, and umbilical hernia. - No seizures |
n/a |
| LaPointe 2014 | F(38y) | c.2002C>T exon13, p.(Gln668Ter) | - Dilated aortic root - Dilated thoracic ascending aorta |
- Mild AR. PDA, bruising - Seizures |
PDA repaired at 18 months |
AR = aortic regurgitation. AVR = aortic valve replacement. AV= aortic valve. Bentall = Bentall cardiac surgical procedure to replace the aortic valve, aortic root, and ascending aorta. EDS = Ehlers Danlos Syndrome. LA = left atrium. MR = mitral regurgitation. PASP = pulmonary arterial pressures PDA = patent ductus arteriosus. PFO = patent foramen ovale. MVP = mitral valve prolapse. VSD = ventricular septal defect.
*
= relationship with another patient with *.
**
= relationship with another patient with **.
++
= Additional cardiac follow-up information ascertained since publication.