Neonatal Marfan Syndrome — A Case Report

Case Report
Acta Cardiol Sin 2004;20:1715
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
CASE REPORT
Marfan syndrome is rarely diagnosed early in neonatal
or young age. Neonatal Marfan syndrome is a
congenital abnormality with atypical features of Marfan
syndrome at an early stage, and it presents the appearances
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 mutation
tendency without family history was found in
neonatal Marfan syndrome. More severe cardiovascular
complications and poor prognosis were noted from neonatal
Marfan syndrome. Higher morbidity and mortality
rates during young age were also pointed out than classic
Marfan syndrome.
Early diagnosis and realization of differences between
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 Marfan
syndrome and summarize this disease.
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
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, respectively.
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 elbows,
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. aortic
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 regurgitation
(MR)(++), tricuspid valve regurgitation (TR)(++),
pulmonary valve regurgitation (PR)(++), aortic valve regurgitation
(AR)(++), and congestive heart failure.
After consulting geneticist, the neonatal Marfan syn-
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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.
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 inhibitor
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-yearold
child by the French pediatrician Antoine Marfan in
1896, 1 is a dominantly inherited connective tissue disease
with a wide range of phenotype severity in the
skeletal, ocular and cardiovascular systems. The prevalence
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 chromosome
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;20:1715 172

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 contractures 1,4,6 47-64% Uncommon
Cardiovascular characteristics 1,11
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.
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 patients
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 regurgitation,
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 regurgitation
is the main reason of death in neonatal MFS
within the first year of life, but aortic dissection or rupture
is the major cause of death of classic MFS during
33.5 years of life 8,9 (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
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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.
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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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