Infantile Marfan Syndrome Research Articles

VP16.08: Prenatal detection of infantile Marfan syndrome: a case report

VP16.08: Prenatal detection of infantile Marfan syndrome: a case report

Ascending aorta and aortic root replacement (with or without valve sparing) in early childhood: surgical strategies and long-term outcomes.

Aortic root and ascending aorta replacements (AARs) are rarely required in the paediatric population. We report here a series of AAR performed in young children using different surgical techniques. Between 1995 and 2017, 32 children under the age of 10 years (median age 5.4 years) underwent AAR procedures at our institution. Twenty-two (69%) had a connective tissue disease (infantile Marfan syndrome or Loeys-Dietz syndrome). We performed 11 AAR using a composite graft with a mechanical prosthesis and 21 valve-sparing procedures (10 Yacoub operations and 11 David operations). Median follow-up for operative survivors was 7.7 years (interquartile range 4.2-12.8 years). The cardiac-related early mortality rate was 6%. Patient survival was 91% at both 1 and 10 years. Eleven survivors (38%), all with a status of post-valve-sparing procedure, required an aortic root reintervention with an aortic valve replacement after a median interval of 4.2 years. Interestingly, only patients with infantile Marfan syndrome tended to be associated with risk of reoperation. Aortic root and AARs are safe in young children whatever the surgical procedure. Aortic valve-sparing procedures show good long-term results except in children with infantile Marfan syndrome whose ineluctable aortic annulus dilatation or aortic valve regurgitation requires reintervention after a short period.

Aortic valve replacement by mechanical prosthesis in children: A positive long-term outcome including for patients with an infantile Marfan syndrome

Aortic mechanical valve replacement (AVR) in children, is commonly associated with a high complication rate and a poor long-term prognosis, especially in children with infantile Marfan syndrome (IMS). We reviewed the clinical and surgical records of patients undergoing AVR at our institution between 2000 and 2017. Sixty-five children (49 boys and 16 girls) required 67 AVR at a median age of 12.5 years (range: 7 months to 17.9 years) and a median weight of 41.7 kg (range: 7.5 to 110 kg). Fourteen patients (21.5%) had a connective tissue disorder diagnosed in early childhood (IMS or Loeys–Dietz syndrome or osteogenesis imperfecta). Median follow-up for operative survivors was 4.6 years (IQR: 2.0–9.0 y, up to 16 y, 94% complete). Global cardiac-related mortality was low 6% ( n = 4) and occurred mainly in the first post-operative days caused by acute bleeding. One-year, five-year and ten-year survival was respectively 94%, 91% and 91%. Among survivors, the 10-year freedom from reoperation was 82%. Complications after AVR included heart block requiring pacemaker implantation (5%), bleeding (4%), stroke (11%) and endocarditis (4%). There was no prosthesis thrombosis. All the patients with an IMS ( n = 12) had associated a moderate to severe aortic valve regurgitation and a significant aortic root dilatation. They required an ascending aorta replacement by composite graft concomitantly the AVR (Bentall procedure). Eight of these (73%) had previous aortic root replacement with a valve sparing technique (Yacoub or Tirone–David procedures). All patients with IMS survived. They remained free from aortic reoperation except one who required a larger aortic prosthesis 9 years later. Long-term results after AVR are excellent. Complications associated with surgery and long-term anticoagulation are rare. This study gives confidence in aortic mechanical prosthesis valve replacement including for children with an infantile MS.

Replacement of the ascending aorta in early childhood: Surgical strategies and long-term outcome

Ascending aorta replacement (AAR) is a rare surgical procedure required in the paediatric population. The classical indication is infantile connective tissue diseases, but AAR is also increasingly performed after neonatal repairs of congenital heart diseases. Between 1995 and 2017, 32 infants under the age of 10 years underwent AAR procedures at our institution. Twenty-one of them (66%) had a connective tissue disease [infantile Marfan syndrome (IMS) or Loeys–Dietz syndrome] while the rest had undergone a neonatal surgery including aortic valve or root. Ten of all (31%) associated a bicuspid aortic valve. The median age and the median weight were respectively 5.3 years (range: 7 months to 9.7 y) and 18 kg (range: 5.8 to 55 kg). Median follow-up for operative survivors was 7.7 years (IQR: 4.2–12.8 y, up to 23 y, 100% complete). Irrespective of the size of the aortic aneurysm at the time of surgery, we performed 11 AAR using a composite graft with mechanical prosthesis (median size 21 mm) and 21 valve-sparing procedures (10 Yacoub operations and 11 David operations). Cardiac-related mortality was 6% and was significantly associated with the Z-score of the aortic root (9.3 ± 1 vs. 6.7 ± 1.8, P = 0.048). Both the one-year and ten-year patient survivals were 91%. Eleven of survivors (38%) required a reintervention after a median time of 4.2 years. All of these latter had undergone an initial valve-sparing procedure. Interestingly, after multivariate logistic regression analysis, only IMS condition remained correlated with the over-risk of reoperation ( P = 0.026). Ascending aorta replacement independently of the surgical procedure is safe in infants, especially when it is performed before giant aortic root dilatation. In IMS, our data suggest that composite graft use with mechanical prosthesis should be preferred to limit the risk of reoperation related to aortic valve regurgitation.

Replacement of the ascending aorta in early childhood: Surgical strategies and long-term outcome

Ascending aorta replacement (AAR) is a rare surgical procedure required in the paediatric population. The classical indication is infantile connective tissue diseases, but AAR is also increasingly performed after neonatal repairs of congenital heart diseases. Between 1995 and 2017, 32 infants under the age of 10 years underwent AAR procedures at our institution. Twenty-one of them (66%) had a connective tissue disease (Infantile Marfan Syndrome IMS or Loeys-Dietz Syndrome) while the rest had undergone a neonatal surgery including aortic valve or root. Ten of all (31%) associated a bicuspid aortic valve. The median age and the median weight were respectively 5.3 years (range, 7 months to 9.7 y) and 18 kg (range, 5.8 to 55 kg). Median follow-up for operative survivors was 7.7 years (IQR 4.2–12.8 y, up to 23 y, 100% complete). Irrespective of the size of the aortic aneurysm at the time of surgery, we performed 11 AAR using a composite graft with mechanical prosthesis (median size 21 mm) and 21 valve-sparing procedures (10 Yacoub operations and 11 David operations). Cardiac-related mortality was 6% and was significantly associated with the Z-score of the aortic root (9.3 ± 1 vs. 6.7 ± 1.8, P = 0.048). Both the one-year and ten-year patient survivals were 91%. Eleven of survivors (38%) required a reintervention after a median time of 4.2 years. All of these latter had undergone an initial valve-sparing procedure. Interestingly, after multivariate logistic regression analysis, only IMS condition remained correlated with the over-risk of reoperation ( P = 0.026). Ascending aorta replacement independently of the surgical procedure is safe in infants, especially when it is performed before giant aortic root dilatation. In IMS, our data suggest that composite graft use with mechanical prosthesis should be preferred to limit the risk of reoperation related to aortic valve regurgitation.

Infantile Marfan syndrome in a Korean tertiary referral center.

PurposeInfantile Marfan syndrome (MFS) is a rare congenital inheritable connective tissue disorder with poor prognosis. This study aimed to evaluate the cardiovascular manifestations and overall prognosis of infantile MFS diagnosed in a tertiary referral center in Korea.MethodsEight patients diagnosed with infantile MFS between 2004 and 2014 were retrospectively evaluated.ResultsTheir median age at the time of diagnosis was 2.5 months (range, 0–20 months). The median follow-up period was 25.5 months (range, 0–94 months). The median length at birth was 50.0 cm (range, 48–53 cm); however, height became more prominent over time, and the patients were taller than the 97th percentile at the time of the study. None of the patients had any relevant family history. Four of the 5 patients who underwent DNA sequencing had a fibrillin 1 gene mutation. All the patients with echocardiographic data of the aortic root had a z score of >2. All had mitral and tricuspid valve prolapse, and various degrees of mitral and tricuspid regurgitation. Five patients underwent open-heart surgery, including mitral valve replacement, of whom two required multiple operations. The median age at mitral valve replacement was 28.5 months (range, 5–69 months). Seven patients showed congestive heart failure before surgery or during follow-up, and required multiple anti-heart failure medications. Four patients died of heart failure at a median age of 12 months.ConclusionThe prognosis of infantile MFS is poor; thus, early diagnosis and timely cautious treatment are essential to prevent further morbidity and mortality.

Abstract 19633: Comparison of Angiotensin II Receptor Blocker versus Beta-blocker Therapy in Genetically Classified Children With Marfan Syndrome

Background: Children with Marfan syndrome (MFS) treated with angiotensin II receptor blocker (ARB) or beta-blocker (BB) therapy show a reduction in the rate of aortic root (AR) growth, yet substantial variability in effect remains. Adult data suggests that patients with haploinsufficient (HI) mutations may be more responsive to ARBs compared with dominant negative (DN) mutations. This study sought to assess the effect of genotype on the rate of AR growth in children treated with either ARB or BB. Methods: A retrospective review of all individuals with MFS assessed at our institution since 1980 was undertaken; those with ≥2 echocardiograms a minimum of 1 year apart and a documented disease-causing fibrillin-1 (FBN1) mutation were included. One patient with infantile MFS was excluded given extremely AR growth. Genotypes were classified by predicted protein effect as either HI or DN. Multivariable longitudinal linear regression analysis was used to compare average rate of AR growth by genotype and medical therapy using serial echocardiographic data. Results: Overall 41 children were included, including 18 with HI and 23 with DN mutations. Males comprised 58%. There was no difference in median age at first echo (HI 5.4 years, IQR 3.9-9.3 vs. DN 5.2 years, IQR 3.4-10.6 years, p=0.97), follow-up time (HI 5.8 years, IQR 4.6-8.2 vs. DN 4.9 years, IQR 3.3-8.7, p=0.35), AR dimension (HI 26 mm, IQR 23-29 vs DN 26 mm, IQR 22-37, p=0.81), or AR z-score (HI 3.0, IQR 2.3-4.0 vs DN 3.4, IQR 2.4-4.2, p=0.58). AR growth rate was greater in children with DN mutations (z-score annual change HI -0.04 vs DN +0.07, p<0.0001). When evaluating AR growth only in patients on ARB or BB monotherapy, patients on ARB with DN mutations grew significantly faster than those on BB therapy with DN mutations (p=0.02). Conclusions: In our cohort, patients with MFS and DN mutations had slower growth on BB therapy compared to those on ARB therapy. Genetic testing may play an important role in targeted medical therapy in MFS.

Abstract 18473: Rates and Risk Factors for Faster Aortic Root Growth in Pediatric Patients with Marfan Syndrome

Background: Marfan Syndrome (MS) is associated with progressive aortic dilation and aortic dissection. Aortic dissection is typically preceded by aortic dilation. The goal of this study is to identify factors associated with faster rates of aortic root dilation in children with MS. Methods: Patients undergoing serial transthoracic echocardiograms (TTE) with MS were retrospectively identified from an institutional database. Those with >2 TTEs over 1 year apart and <21 years of age at first TTE were included. TTEs performed after aortic surgery were excluded. Using multivariable longitudinal linear regression analysis, sex, medication, presence of ectopia lentis, need for scoliosis surgery and infantile type of MS were evaluated for associations with rate of change in aortic root dimension and aortic root z-score over time. Results: Of 240 patients with MS, 146 were included. Median age at first TTE was 8.1 yrs (range 0-20.9 years), median length of follow up 6.5 years (range 1.0-20.1 years), and median number of studies was 8 (range 2-25). Sixty-one percent were male. Of the 146 patients, 123 (84%) were documented to be on medical therapy: 14 angiotensin receptor blocker (ARB), 66 B-Blocker (BB), 10 prior history of both, 5 BB+ARB, 27 were in the Pediatric Heart Network medication trial, 1 ACE inhibitor. Sixteen patients underwent root replacement surgery at a median age of 14.6 years (range 1.8-24). No patients had aortic dissection. Three patients had infantile MS. All of these patients underwent root replacement at 1.8, 2 and 4 years of age. Two underwent subsequent aortic root replacement at 6 and 8 years old. Mean rate of aortic root growth in the cohort was 0.12cm/year, and mean change in z-score was 0.02/year (p=0.23 compared to expected rate of no change). The only variable associated with faster root growth was infantile MS (1.3cm/year, p<0.001; z-score change of 6.9/year, p<0.001). There was no significant difference in the rate of aortic root growth between patients who received therapy with BB vs. ARB vs. BB+ARB. Conclusions: Children with MS did not have a significant change in aortic root z-score over time, and the only factor associated with more rapid aortic root growth was infantile type MS.

Infant Repair of Massive Aortic Aneurysm With Prosthetic Valved Conduit

A 4-month-old child with severe infantile Marfan syndrome underwent successful repair of an extremely dilated aortic root and severe aortic valve insufficiency using a prosthetic valved conduit.

Dilatation of the Great Arteries in an Infant with Marfan Syndrome and Ventricular Septal Defect

We describe an infant presenting with contractures of the fingers, a large ventricular septal defect (VSD), and severe pulmonary artery dilatation. He had clinical and echocardiographic features of both neonatal or infantile Marfan syndrome (MFS) and congenital contractural arachnodactyly. After surgical VSD closure, the aortic root developed progressive dilatation while the size of pulmonary artery returned to normal limits. Eventually the diagnosis of MFS was confirmed by DNA analysis.

Quadrivalvar Replacement in Infantile Marfan Syndrome

Marfan syndrome (MS) is a connective tissue disease involving the cardiovascular, ocular, and the musculoskeletal systems. MS has variable phenotypic expression and is most often diagnosed in adult life. Infantile-onset MS is rare and is associated with severe cardiovascular manifestations; there is an extremely high mortality during the first 2 years of life. We present a case of a child with severe infantile MS who, during the course of infancy and early childhood, developed aortic root dilatation and polyvalvar insufficiency requiring subsequent successful replacement of the aortic root and of all cardiac valves. To our knowledge, this is the first reported case of quadrivalvar replacement in the pediatric age group.

Severe infantile Marfan syndrome versus neonatal Marfan syndrome

Severe infantile Marfan syndrome versus neonatal Marfan syndrome

Replacement of the ascending aorta in children: A series of fourteen patients

J Thorac Cardiovasc Surg 2002;124:411-3

Marfan Syndrome, Not Marfan’s Syndrome

To the Editor: I read with interest the case of infantile Marfan syndrome reported by Doroshow, Lin, and Milliken.1 But I wish they would not use the possessive form of Marfan syndrome. Use of eponyms for diseases is a common practice in medicine. It often conveys a nice sense of …

Cardiac anomalies complicating congenital contractural arachnodactyly.

A newborn boy with congenital contractural arachnodactyly (CCA) was found to have an atrial septal defect, ventricular septal defect, patent ductus arteriosus, and aortic arch anomalies. These resulted in congestive failure but subsequent progressive dilatation of both great arteries and development of aortic regurgitation were associated with eventual cardiorespiratory failure and death at 11.5 months. Others have noted that cardiac anomalies in CCA may be comparable with those of infantile Marfan's syndrome. Our case further extends the spectrum of cardiac abnormalities in CCA and substantiates that there is overlap with infantile Marfan's syndrome. This fact and our literature review suggest that early and complete cardiac assessment is necessary for appropriate management and evaluation of prognosis in any newborn infant with findings suggestive of either condition.

Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome

Since the clinical, 2-dimensional and Doppler echocardiographic and pathologic findings in infantile Marfan syndrome have not been documented in detail, a study of 9 such infants was performed. The previously reported 64 cases were reviewed and the salient findings in 22 additional cases were discussed. The age at diagnosis in our 9 cases ranged from birth to 12 months (mean 2.7 months). Mitral valve prolapse was demonstrated in all, with mitral regurgitation in 8. Tricuspid valve prolapse was present in 8, with tricuspid regurgitation in 6. Marked aortic root dilatation was present in all, and was progressive. The aortic root assumed a “clover leaf” appearance in the parasternal shortaxis view. Aortic regurgitation was documented initially in 1 patient, and developed during follow-up in 4 of 7 infants. Dilatation of the pulmonary arterial root and pulmonary regurgitation were found in 3 of 7 infants. Severe heart failure associated with mitral or tricuspid regurgitation was present in 7 of the 9 patients. Four infants died during the first year of life. The salient pathologic features were myxomatous thickening and redundancy of the mitral and tricuspid leaflets, marked elongation of chordae tendineae and prominent dilatation of the aortic and pulmonary roots. Histologically, the collagen and elastic fibers were severely disrupted, disarrayed and fragmented with increased interstitial ground substance. These data document that infantile Marfan syndrome is characterized by clinical and morphologic features that are distinctly different from the classic syndrome seen in adolescents and adults. The aforementioned findings should facilitate early clinical and echocardiographic diagnosis of infantile Marfan syndrome.