Neonatal Marfan Syndrome — A Case Report

Hsien-Yu Shih, Wan-Shiung Liu and Te-Jen Chen

Neonatal Marfan syndrome is a rare congenital abnormality with atypical features of Marfan syndrome at an early

stage. Although, neonatal Marfan syndrome is part of Marfan syndrome, its higher morbidity and mortality rate

within young children period are different from those of classic Marfan syndrome noted in older patients. Several

diversities of family history, cardiovascular system and cause of death are pointed out from recent studies.

Key Words: Neonatal Marfan syndrome � Congenital abnormality � Classic Marfan syndrome

INTRODUCTION

Marfan syndrome is rarely diagnosed early in neo-

natal or young age. Neonatal Marfan syndrome is a

congenital abnormality with atypical features of Marfan

syndrome at an early stage, and it presents the appear-

ances of tall stature, thin body build, long arms, legs,

fingers and toes like Marfan syndrome. From genetic

studies, Marfan syndrome is a heritable disorder with

family history on chromosome 15, but spontaneous mu-

tation tendency without family history was found in

neonatal Marfan syndrome. More severe cardiovascular

complications and poor prognosis were noted from neo-

natal Marfan syndrome. Higher morbidity and mortality

rates during young age were also pointed out than clas-

sic Marfan syndrome.

Early diagnosis and realization of differences be-

tween neonatal Marfan syndrome and classic Marfan

could help physicians to treat such kind of patients and

explain to the family. We report a case of neonatal Mar-

fan syndrome and summarize this disease.

CASE REPORT

The patient was a one-day-old male neonate who was

born after 40 weeks gestation via normal delivery in our

hospital. His birth body weight was 3272 grams and the

Apgar scores were 7 and 9 at 1 and 5 minutes, respec-

tively. No disease during the pregnant period of the

mother was noted, nor was any inheritable family disease

noted among the parents. The parents of the neonate were

generally normal-figure appearance (father: age: 33 years

old, body height: 176 cm; body weight: 68 kg; mother:

age: 32 years old, body height: 156 cm; body weight: 53

kg), and without any ocular or cardiovascular disease.

Several bizarre appearances of the neonate were

noted, including: dolicocephaly, arachnodactyly (Figure

1A), pigeon chest (Figure 1B), cyanosis, generalized

pale appearance, rigidity and contracture of bilateral el-

bows, knees, and shoulder joints. Also, Gr. II/VI systolic

murmur over left lower sternal border was found during

acoustic examination.

Cardiomegaly and pulmonary venous congestion

were also detected from chest roentgenography. There

were several abnormal findings from cardiac echo: 1. aor-

tic root were dilatated in the ascending aorta; 2. patent

ductus arteriosus with bi-directional shunt; 3. atrial septum

defect with bi-directional shunt; 4. mitral valve regurgita-

tion (MR)(++), tricuspid valve regurgitation (TR)(++),

pulmonary valve regurgitation (PR)(++), aortic valve re-

gurgitation (AR)(++), and congestive heart failure.

After consulting geneticist, the neonatal Marfan syn-

171 Acta Cardiol Sin 2004;20:171�5

Case Report Acta Cardiol Sin 2004;20:171�5

Received: June 12, 2003 Accepted: February 18, 2004

Department of Pediatrics, Chi-Mei Foundation Hospital, Tainan,

Taiwan.

Address correspondence and reprint requests to: Dr. Wan-Shiung Liu,

Department of Pediatrics, Chi-Mei Foundation Hospital, No. 901,

Chung-Hwa Road, Young-Kang City, Tainan 710, Taiwan.

Tel: 886-6-281-2811 ext. 5592; Fax: 886-6-231-0604;

E-mail: lleoteo@yahoo.com.tw

drome was impressed. The karyotype of the neonate was

46XY. There was no unusual finding pointed out in bilateral

eyes of the patient after consultation of ophthalmologist.

We treated the patient with diuretics and ACE inhib-

itor at the same time due to the detection of congestive

heart failure. The conditions of congestive heart failure

seem not ameliorated, and digoxin was prescribed to

prevent the state becoming worse. However, dilatation

of aorta, MR, TR, AR and congestive heart failure got

worse progressively (Figures 2 A, B) and unfortunately,

the patient expired due to severe congestive heart failure

on the 52nd day after admission.

DISCUSSION

Marfan syndrome (MFS), first described in a 5-year-

old child by the French pediatrician Antoine Marfan in

1896,1 is a dominantly inherited connective tissue dis-

ease with a wide range of phenotype severity in the

skeletal, ocular and cardiovascular systems. The preva-

lence of MFS has been estimated to be approximately 4

to 6 per 100,000 population in the United States,2 and

equally common in males and females.

MFS is a heritable disorder where abnormalities of

fibrillin protein are encoded by the fibrillin-1 gene

(FBN1), a large gene composed of 65 exons on chromo-

some 15q15-q21.3.3 The “neonatal Marfan syndrome” or

“ infantile Marfan syndrome” is a part of MFS whose

atypical features of cardiovascular system with long,

thin spindly physique can be detected at an early stage,4

but the neonatal MFS presents diverseness from older

Marfan syndrome (or “classic Marfan syndrome”). It is

likely a new mutation, not the family-inherited type from

Acta Cardiol Sin 2004;20:171�5 172

Hsien-Yu Shih et al.

Figure 1. Clinical pictures of the patient on day 1 of birth: (A)

Arachnodactyly: The fingers of right hand present longer and thinner.

(B) Chest lateral view of patient. Pigeon chest (sternal convexity

obvious) was noted.

Figure 2. Parasternal long axis view of echocardiography: (A) Day

1: Aortic root dilatation was noted. (the letters “AO” marked area) (B)

Day 51: Aortic root dilatation appeared worse.

the literature.1

The skeletal manifestations of MFS include tall stature,

thin body build, long arms and legs (dolichostenomelia),

long fingers and toes (arachnodactyly), hyperextensibility,

pectus deformity, scoliosis, joint contractures, and narrow,

high-arched palate. Neonatal MFS presents more joint

contracture (67%) than classic MFS. In follow-up, neonatal

MFS also have considerable morbidity due to scoliosis

(32%) and easily dislocatable joint (36%).1

The majority of cardiovascular abnormalities of pa-

tients with MFS are associated with the ascending aorta,

aortic valve, and the mitral valve, of which the most

common are aortic root dilatation, aortic regurgitation,

and mitral valve prolapse.5

The cardiovascular abnormalities in neonatal MFS

differ somewhat from those seen in older patients.

Multivalvular abnormalities are the major frequent cardiac

pathology in children compared to aortic complications in

adults. In these neonates, there are significant mitral,

tricuspid, and pulmonary regurgitations noted, whereas

among adult patients aortic root dilatation, aortic regurgita-

tion, and aortic dissection are predominate.5,6 In addition,

children with MFS have tendency of obvious heart failure.

Cardiovascular problems are responsible for at least

80% of deaths in MFS.7 The main cause and mean age at

death are different between neonatal and classic MFS.

Congestive heart failure with mitral and tricuspid regur-

gitation is the main reason of death in neonatal MFS

within the first year of life, but aortic dissection or rup-

ture is the major cause of death of classic MFS during

33.5 years of life8,9 (Table 1). The neonatal MFS life

span is less than 2 years, due to the reason of severity of

cardiovascular problems.

Neonatal MFS has higher morbidity and mortality

rate within young age than classic MFS, therefore, the

pediatric cardiologist should explain the complications

to the families, and some degree of psychosocial support

may be needed.

REFERENCES

1. Morse RP, Rockenmacher S, Pyeritz RE, et al. Diagnosis and

management of infantile Marfan syndrome. Pediatrics. 1990;86:

888-95.

2. Pyertiz RE, McKusick VA. The Marfan syndrome: diagnosis and

management. N Engl J Med 1979;300:727-77.

3. Dietz HC, Pyeritz RE, Hall BD, et al. The Marfan syndrome

locus: confirmation of assignment to chromosome 15 and

identification of tightly linked markers at 15q15-q21.3. Genomics

1991;9:355-61.

4. Jonathon R Gray, Sarah J Davies. Marfan syndrome. J Med Genet

1996;33:403-8.

5. Roman MJ, Devereux RB, Kramer-Fox R, et al. Comparsion of

cardiovascular and skeletal features of primary mitral valve

prolapse and the Marfan syndrome. Am J Cardiol 1989;63: 317-21.

6. Marsalese DL, Moodie DS, Vacante M, et al. Marfan’s syndrome:

natural history and long-term follow-up of cardiovascular

involvement. J Am Coll Cardiol 1989;14:422-8.

7. Murdock JL, Walker BA, Halpern BL, et al. Life expectancy and

causes of death in the Marfan syndrome. N Engl J Med 1972;286:

804-8.

8. Phornphutkul C, Rosenthal A, Nadas AS. Cardiac manifestations

173 Acta Cardiol Sin 2004;20:171�5

Neonatal Marfan Syndrome

Table 1. Comparison between neonatal Marfan syndrome and classic Marfan syndrome

Neonatal Marfan syndrome Classic Marfan syndrome

Clinical characteristics

Age at death 1,6,11 Less than 2 years 32 � 16 years

Main cause of death 11 CHF associated with MR and TR Aortic dissection or rupture

Family history of Marfan syndrome 1,4,11 Negative in 70-100% Negative in only about 20-30%

Joint contractures1,4,6 47-64% Uncommon

Cardiovascular characteristics1,11

MVP 73-100% 60 to 90%

MR (moderate to severe) 89% 13%

Aortic dilation 80-100% 60-85%

AR 11% 73%

TR 67% Uncommon

PR 22% Uncommon

CHF = congestive heart failure; MVP = mitral valve prolapse; AR = aortic regurgitation; TR = tricuspid regurgitation;

MR = mitral regurgitation; PR = pulmonary regurgitation.

of Marfan syndrome in infancy and childhood. Circulation

1973;47:587-95.

9. Towbin JA. Genetic syndromes and clinic molecular genetics. In:

Garson A Jr, Bricker JT, Fisher DJ, et al. The Science and Practice

of Pediatric Cardiology. 2nd ed. Baltimore: Williams & Wilkins,

1998:2627-99.

Acta Cardiol Sin 2004;20:171�5 174

Hsien-Yu Shih et al.

Case Report Acta Cardiol Sin 2004;20:171−5

新生兒 Marfan症候群 — 病例報告

施憲佑 劉萬雄 陳德人台南縣 財團法人奇美醫院 小兒心臟科

新生兒 Marfan 症候群為一種染色體先天性異常的疾病。在新生兒時期即表現 Marfan 症候群的病徵是相當罕見。雖然新生兒 Marfan 症候群是屬於 Marfan 症候群的一部份，但是其所特有的高死亡率和高罹病率特徵卻不同於一般典型 Marfan 症候群。從近期文獻中顯示，新生兒 Marfan 症候群在心臟血管系統及家族遺傳與一般典型的 Marfan 症候群有著許多顯著的不同點。因此，藉由本文中罕見的病例以及文獻回顧來比較兩者的不同。

關鍵詞：新生兒Marfan症候群、先天性異常、典型Marfan症候群。

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