|Year : 2016 | Volume
| Issue : 2 | Page : 128-130
Unremitting congestive heart failure: Neonatal Marfan syndrome
Euden Bhutia, Pradeep Kumar, Sunil Kishore, Dinesh Kumar Yadav
Department of Neonatology and Pediatric Medicine, Division of Pediatric Cardiology, PGIMER, Dr. RML Hospital, New Delhi, India
|Date of Web Publication||8-Apr-2016|
Dinesh Kumar Yadav
Department of Paediatrics, Dr. Ram Manohar Lohia Hospital, Room No. 238, OPD Block, New Delhi
Source of Support: None, Conflict of Interest: None
Neonatal Marfan Syndrome is a rare congenital abnormality with atypical features of Marfan Syndrome and poor prognosis. Multi-valvular involvement is major cardiac manifestation, and heart failure is the most common cause of death.
Keywords: Aortic root dilatation, blue sclera, enophthalmos, Neonatal Marfan Syndrome
|How to cite this article:|
Bhutia E, Kumar P, Kishore S, Yadav DK. Unremitting congestive heart failure: Neonatal Marfan syndrome. J Clin Neonatol 2016;5:128-30
| Introduction|| |
Marfan Syndrome is rarely diagnosed in the neonatal period. Neonatal Marfan Syndrome is the severest phenotype of this disease and has a poor prognosis. Early diagnosis and realization of differences between Neonatal Marfan Syndrome and classical Marfan Syndrome could help pediatricians to treat such kind of patients and prognosticate. We are reporting a case of Neonatal Marfan Syndrome with gross dilatation of aortic root and sinuses presenting in the neonatal period with congestive heart failure. There are few case reports of Neonatal Marfan Syndrome from our country.
| Case Report|| |
A 40-day-old baby was referred to our center with complaints of a cough, respiratory distress, and suck rest cycle since one week of age. His mother had an uneventful pregnancy, and the baby was normally delivered at term. The parents and other siblings had normal body habitus. Physical examination showed a long, thin, spindly physique with a length of 65.0 cm (+4 z-score), weight of 3.5 kg (weight/length <−3 z-score), and an arm span of 67.0 cm (arm span/length was 1.03). Facial features included dolichocephaly, enophthalmos, downward slanting palpebral fissure, malar hypoplasia, retrognathia, large ears, and blue sclera. Skeletal features included scoliosis, arachnodactyly, and restrictive movement at bilateral elbow joints [Figure 1]. Fingers and toes were abnormally long, and thumb sign was positive. The skin was non-translucent with no easy-bruisability. There was no craniosynostosis, cleft palate, bifid uvula, and the hernial sites were normal.
|Figure 1: Clinical photograph showing: (a) Slender long fingers, (b) thumb sign, (c) deep seated orbits and retrognathia, (d) extension deficit at elbow joint|
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Cardio-respiratory examination revealed tachypnea, subcostal and intercostals retractions, tachycardia, and fine creps with a hyperdynamic precordium and Grade III and IV systolic murmur and a gallop rhythm. The abdomen was soft, and the liver was palpable 4 cm below the costal margin. A dysmorphic disorder was not primarily recognized as Neonatal Marfan Syndrome despite the classical facial stigmata, skeletal, and cardiovascular manifestations.
Investigation revealed a normal hemogram and electrolytes. Sepsis screen was negative. Chest roentgenography showed cardiomegaly and pulmonary plethora. Electrocardiography showed sinus tachycardia with the normal axis.
On echocardiography aortic valve was tricuspid and the aortic root was grossly dilated (annulus [1.4 cm, z-score >+3], aortic sinuses [3.3 cm, z-score >+4], and sinotubular junction [1.7 cm, z-score >+3]) with severe aortic regurgitation [Figure 2]. Mitral and tricuspid valve prolapse was evident with moderate regurgitation. The left ventricle was dilated with an ejection fraction of 30%. The pulmonary root diameters were normal. Ultrasound sonography abdomen and cranium were normal. Mutation analysis could not be performed because of unaffordability. Parents refused any surgical intervention. The patient was managed with digoxin and diuretics and subsequently on carvedilol and angiotensin converting enzyme (ACE) inhibitors. He had multiple admissions due to congestive cardiac failure and succumbed to death at 3 months of age.
|Figure 2: Echocardiography (a) parasternal view showing dilated aortic sinus. (b) suprasternal view showing dilated ascending aorta|
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| Discussion|| |
Marfan Syndrome is an autosomal dominant disorder of connective tissue with ocular, skeletal, cardiovascular, integumentary, pulmonary, and neurological features. It is caused by missense mutations in FBN1 gene, composed of 65 exons on chromosome 15q21. Mutations are located in the region of exon 24-32.  The gene encodes fibrillin-1, a principle component of extracellular matrix microfibrils. The incidence of Marfan Syndrome is 6 per 10000 in the United States.  The diagnosis is often missed and if so made there is always a diagnostic dilemma between the early presentation of classical Marfan Syndrome to that of Neonatal Marfan Syndrome.
Neonatal Marfan Syndrome is phenotypically and genetically distinct from classical Marfan Syndrome. It usually presents at birth and is diagnosed during the neonatal or infantile period while the classical form is usually diagnosed during adolescence. A positive family history is usually present
Neonatal Marfan Syndrome is characterized by multivalvular involvement which is uncommon in classical Marfan Syndrome. Severe cardiac manifestations include early aortic root dilatation, atrioventricular valve prolapse, and severe valve regurgitation resulting in intractable heart failure. Whether medical or surgical treatment of Neonatal Marfan Syndrome improves prognosis is unclear. Early death occurs usually below 2 years of age due to persistent heart failure whereas in classical Marfan death is due to aortic dissection and rupture in the third decade of life.  The universal Marfan-data base-FBN1 (UMD-FBN1: http://www.umd.be ) published in 2011, reported 38 deaths among 60 individuals with Neonatal Marfan Syndrome; 82% died before the age of 1 year.  The cause of death in 88% was heart failure. Our patient presented with persistent heart failure had multivalvular involvement and a dilated aortic root and died by the end of the third month on subsequent admission due to intractable heart failure.
Our patient had a wasted look with very loose skin, a long and spindle physique, and the characteristic phenotype of Neonatal Marfan Syndrome: Dolichocephaly, enophthalmos, down-slanting palpebral fissures, malar hypoplasia, retrognathia, tall stature, thin body build, long arms and legs (dolichostenomelia), arachnodactyly, pectus carinatum, scoliosis, bilateral elbow joint contractures, and high-arched palate.
Neonatal Marfan Syndrome presents with more joint contracture (67%) than classical Marfan Syndrome. Later, they may develop scoliosis (32%) and easily dislocated joints (36%).
The diagnosis of Marfan Syndrome is clinically based on fulfillment of revised Ghent diagnostic criteria.  A patient fulfilling certain combinations of aortic dilation, ectopia lentis, systemic features, family history, and FBN1 mutation can be diagnosed as Marfan Syndrome. A total of 20 points are provided to systemic features, and >7 points are required to be fulfilled. Our patient fulfilled the Ghent criteria (Aortic root dilatation [z-score >2] and 8 score of the systemic manifestations) to qualify as Marfan Syndrome.
Beta blockers (propranolol, atenolol) and ACE inhibitors (enalapril) have been found to be effective in halting and even reversing the aortic dilatation in Marfan Syndrome. However, there are no major studies to validate the same effect of these drugs on neonates with Marfan Syndrome. Surgery may be necessary to replace or repair the aortic valve and root, but surgery is difficult in Neonatal Marfan Syndrome due to significant mortality and morbidity. More so there is a high probability of complete heart block, thrombosis, and stroke in this age group.  Heart transplantation is the last resort for these patients.  The long‐term prognosis is very poor, usually because of progressive valve dysfunction. This case is being reported not only in view of the missed diagnosis in the neonatal period and the rarity of this condition but also to emphasize upon the genetic and phenotypic differences that exist from the classical Marfan and the associated poor prognosis with this entity.
Declaration of Patient Consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]