We report about a successful heart failure therapy with carvedilol in two children with neonatal Marfan syndrome (nMFS). As shown in Case 1, double valve replacement in an infant with neonatal Marfan syndrome is feasible but its benefit on long term is uncertain. Excluding our patient, 3 infants with nMFS from the literature died early after cardiac surgery. Our second case is a unique patient who survives nMFS despite diaphragmatic herniae, dilated neonatal cisterna magna and severe atrioventricular valve insufficiencies. Treated with 0.7 mg/kg/day Carvedilol since his seventh month of life, he never developed severe heart failure. However despite his good health status at the age of 9 years, a progressive aortic root dilatation and left conornary aneurysm are still waiting for surgical repair.
Marfan syndrome (MFS) is a rare generalized connective tissue disease with an estimated prevalence of 7 to 17 per 100,000. It is associated with mutations of the Fibrillin 1 gene located on chromosome 15q21. Neonatal MFS (nMFS) is regarded as an independent entity with most mutations in the region of exon 24 - 32 [
We report on 2 infants with neonatal MFS exhibiting heart failure as infants already due to severe atrioventricular valve prolapse and severe valve regurgitation. Based upon our investigations about beta blockers in infants’s heart failure [
A female infant was born at 40 weeks gestational age to a 34-year-old first gravida by spontaneous vaginal delivery. Family history for MFS was negative. The birth weight was 3380 g and the length 53 cm. Apgar scores were 9 after one minute and 10 after 5 minutes. Arachnodactyly, hyperflexible joints with contractures, highly arched palate, dolichocephaly, enophthalmus, retrognathia, loose skin and low set dysplastic ears were present. Echocardiography at the first month of life showed dilatation of the ascending aorta, prolapse of both atrioventricular valves, grade II insufficiency of the mitral valve, grade III insufficiency of the tricuspid valve, grade I insufficiency of the aortic and pulmonary valve. The aortic root was enlarged, diameter of the sinus of valsalva measuring 16 mm (z-value: +2). The pulmonary root diameters were normal. Left ventricular enddiastolic diameter was enlarged measuring 26 mm and fractional shortening slightly decreased by 27%.
The girl was treated for congestive heart failure with Carvedilol (slowly increasing doses up to a final dosage of 0.7 mg/kg/day). She started to thrive and gained 2 kg of weight within three months.
Clinical symptoms of congestive heart failure were discrete only. At the age of 5 month symptoms of congestive heart failure increased due to progression of mitral and tricuspid insufficiency and significant cardiomegaly developed. Additional medication with digoxin and diuretics could not improve her clinical situation on long term. Thus mitral (SJM 27 mm) and tricuspid valve replacement (Carpentier-Edwards SAV bioprothesis 31 mm) was performed at the age of 7 months and a bodyweight of 6.2 kg. The patient recovered quickly after surgery and cardiomegaly was reduced significantly. After surgery supraventricular tachycardia occurred and was successfully treated with Sotalol. The patient was discharged with Digoxin, Captopril, Spironolactone and Sotalol medication. Heart failure had improved, valve function was normal and the patient continued to thrive. However three month later she died at home with signs of rapid progressive left ventricular failure without evidence of valve dysfunction or persistent tachycardia.
A male infant was born at 39 weeks gestational age to a 31-year-old fourth gravida, second para, by cesarean section. Family history for MFS was negative. However the mother had two abortions and one brother died at his first day of life due to a dystrophic disorder with lung hypoplasia. The birth weight of our patient was 3180 g, the length 51 cm. Apgar scores were 9 after one minute and 10 after 5 minutes. A dysmorphic disorder was not primarily recognized as neonatale marfan syndrome despite facial stigmata, highly arched palate, dolichocephaly, enophthalmus, retrognathia, loose skin and low set dysplastic ears. Cranial MR imaging had shown a dilated neonatal cisterna magna [
Echocardiographic aortic root dimensions compared to normal children [10] , left ventricular diameter and prolongation of QRS Duration in a standard ECG in a boy with neonatal marfan syndrom form seventh month up to 9 years related to body surface area
normal. He suffers from heart failure Ross Score 4, no failure to thrive and elevated NT-Pro-BNP levels up to 1149 pg/ml. nMFS was diagnosed and the boy was treated with Carvedilol (slowly increasing doses up to a final dosage of 0.7 mg/kg/day). Later thoracic X-ray showed right side diaphragmatic herniae with hepatic tamponade. Intracapsular lens extraction was performed.
A fibrillin-1 mutation was found: heterozygote deletion exons 19 - 21 (ex19ex21del, FBN1). Today his height is 5 cm above the 97th percentile, his early macrocephaly is now in normal range and despite severe atrioventricular valve insufficiencies he never developed severe heart failure. He currently goes to school and performs low intensity sports. However the aortic root and his left ventricle was progressively dilated (
Both children had typical clinical signs of nMFS with predictors for a bad prognosis. Obviously, the new mutation of the Fibrillin 1 gene in the exon region 18 - 24 in Case 2 causes nMFS. It remains unclear if the early death of his brother is also caused by this mutation and whether the bad prognosis of this mutation is the cause. For the first time, we report about a successful heart failure therapy with carvedilol in nMFS. As shown in Case 1, double valve replacement in an infant with neonatal Marfan syndrome is feasible but its benefit on long term is uncertain. Excluding our patient, 3 infants with nMFS from the literature died early after cardiac surgery [