American Journal of Medical Genetics 139A:1 (2005)
Editorial Comment
Severe Infantile Marfan Syndrome Versus
Neonatal Marfan Syndrome
In the following study, Kim Summers and co-workers
describe a child with Marfan syndrome that was recognized
at birth. Originally the authors called this ‘neonatal Marfan
syndrome’ but the Editorial Board did not agree with this label.
This requires an explanation.
Some authors state that there is no such entity as ‘neonatal
Marfan syndrome,’ and find neonatal Marfan syndrome the
more severe end of the continuum of the fibrillinopathies.
Others split Marfan syndrome, and label all cases with
unusually severe symptoms at birth as having ‘neonatal
Marfan syndrome.’ In this discussion, it seems wise to go back
to the meaning of splitting or lumping. Usually splitting is
justified, if it adds to our understanding, care, prognosis, or
counseling of patients and their families. If that is not the case,
one can as well refrain from splitting and lump them together.
Marfan syndrome is always present from birth. Recognition
depends on how careful a newborn child is investigated and
how experienced the investigator is in the area of connective
tissue disorders. When the suspicion is increased, for instance,
because one of the parents has Marfan syndrome symptoms
will usually be recognized. The sheer presence of symptoms of
Marfan syndrome at birth is therefore not sufficient to allow
the diagnosis ‘‘neonatal Marfan syndrome.’’
So what then makes the difference for the patient and the
parents, and allows us to make this diagnosis? Newborn
children with an expressed form of Marfan syndrome and with
neonatal Marfan syndrome share severe skeletal or eye
problems: both can have ectopia lentis, camptodactyly,
arachnodactyly, joint contractures, muscle hypoplasia, and
loose skin. These symptoms can have a major impact on the
patients, but will be treated similarly in both groups of
patients, are not life threatening, and will not determine the
prognosis.
There are however two symptoms that are uncommon in
severe Marfan syndrome presenting at birth, but very common
in neonatal Marfan syndrome: congenital emphysema, and
mitral and/or tricuspid valve insufficiency. Pulmonary emphy-
sema occurs in adults with Marfan syndrome, and occasionally
in later childhood, but not in infancy. The cardiac symptoms
are also different from the problems later in life: in the neonatal
form it consists of valve problems that relentlessly progress,
lead to congestive heart failure, and almost always end in an
earlier demise in the first 2 years of life. Patients with neonatal
Marfan syndrome often have an enlarged aortic root, but that is
not the determining problem in them. While at an older age the
*Correspondence to: Raoul C.M. Hennekam, M.D., Ph.D., Great
Ormond Street Hospital for Sick Children, Institute of Child
Health, 30 Guilford St., London WC1N 1EH UK.
E-mail: hennekam@planet.nl
Received 23 August 2005; Accepted 25 August 2005
DOI 10.1002/ajmg.a.30979
ß 2005 Wiley-Liss, Inc.
aortic problem is the major issue, and usually mitral/tricuspid
valve insufficiency is of less importance. The two clinical
features of emphysema and valve insufficiency are therefore
different from the normal features, and both have important
consequences for prognosis, treatment, and counseling.
Isolated occurrence of Marfan syndrome in a neonate is not
the determining factor, as 25–35% of patients with the
common type of Marfan syndrome are sporadic. The localiza-
tion of the mutation within the so called ‘neonatal region’ (exon
24–32) of fibrillin I is not determining either, as patients with
classical Marfan syndrome have been found to harbor muta-
tions in this region too.
Therefore, it seems prudent to diagnose an early onset form
of Marfan syndrome in the patient described by Summers et al.
but not as neonatal Marfan syndrome. Some authors have
suggested naming this early form of Marfan syndrome
‘infantile Marfan syndrome’ [Geva et al., 1990; Morse et al.,
1990]. Neonatal Marfan syndrome should be restricted to
neonates that show severe mitral and/or tricuspid valvular
insufficiency and infantile pulmonary emphysema in addition
to the common symptoms of ectopia lentis, arachnodactyly,
joint contractures and loose skin [Booms et al., 1999; Revencu
et al., 2004].
ACKNOWLEDGMENTS
I thank Professor Anne De Paepe (Ghent) for her comments
on the manuscript.
REFERENCES
Booms P, Cisler J, Mathews KR, Godfrey M, Tiecke F, Kaufmann UC, Vetter
U, Hagemeier C, Robinson PN. 1999. Novel exon skipping mutation in
the fibrillin-1 gene: Two ‘hot spots’ for the neonatal Marfan syndrome.
Clin Genet 55:110–117.
Geva T, Sanders SP, Diogenes MS, Rockenmacher S, Van Praagh R. 1990.
Two-dimensional and Doppler echocardiographic and pathologic char-
acteristics of the infantile Marfan syndrome. Am J Cardiol 65:1230–
1237.
Morse RP, Rockenmacher S, Pyeritz RE, Sanders SP, Bieber FR, Lin A,
MacLeod P, Hall B, Graham JM. 1990. Diagnosis and management of
infantile Marfan syndrome. Pediatrics 86:888–895.
Revencu N, Quenum G, Detaille T, Verellen G, De Paepe A, Verellen-
Dumoulin C. 2004. Congenital diaphragmatic eventration and bilateral
uretero-hydronephrosis in a patient with neonatal Marfan syndrome
caused by a mutation in exon 25 of the FBN1 gene and review of the
literature. Eur J Pediatr 163:33–37.
Raoul C.M. Hennekam*
Clinical and Molecular Genetic Unit
Institute of Child Health
Great Ormond Street Hospital for
Children, London, United Kingdom
Department of Paediatrics,
Academic Medical Center, Amsterdam
The Netherlands