A case report of Marfans Syndrome patient with epilepsy-A Rare concomitance

Abstract

Marfans syndrome is a disorder of the connective tissue inherited as an autosomal dominant condition of variable expression and its classical form comprises of skeletal, cardiovascular and ocular abnormalities. It is attributed as a defect in the mutation in the fibrillin gene. The syndrome has a wide range of expression from mild to the severe forms. Sometimes the symptoms are so mild that only few of the symptoms occur. In most cases, the disease progresses with age and symptoms of Marfans syndrome become noticeable as changes in the connective tissue occur. Most of the reported cases so far are associated with cardiovascular abnormalities. We report a case of Marfans syndrome associated with epilepsy.

[J Contemp Med 2012; 2(1.000): 33-37]

Full text

Journal of Contemporary Medicine 2012; 2(1): 33-37 Dsouza et al.
33
Case report / Olgu sunusu
A case report of Marfans Syndrome patient with epilepsy-A Rare
concomitance
Epilepsi ile birlikte Marfan Sendromu olgu sunusu- nadir bir birliktelik
Deepa Dsouza
1
, Subhas Babu G
1
, Shishir Ram Shetty
1
, Preethi Balan
1
Özet
Marfan Sendromu, değişken ekspresyon durumlarının olduğu
otozomal dominant kalıtımlı bir bağ dokusu bozukluğudur ve klasik
biçimiyle, iskelet, kardiyovasküler ve oküler anomalileri
kapsar. Bu fibrillin genindeki mutasyon bir kusur olarak atfedilir.
Sendrom hafiften şiddetliye geniş bir ifade yelpazesine
sahiptir. Bazen semptomlar çok belirsizdir, sadece birkaç semptom
oluşabilir. Çoğu durumda hastalık yaşla birilikte ilerler, bağ
dokusunda değişikliklerin belirmesi ile Marfan Sendromu
belirginleşir. Bugüne kadar bildirilen vakaların çoğu kalp-
damar anormallikleri ile ilişkilidir. Biz epilepsi ile ilişkili Marfan
Sendromu olgusunu sunduk
Anahtar kelimeler: Marfan Sendromu, Araknodaktili,
Mavi sklera, Epilepsi.
Abstract
Marfans Syndrome is a disorder of the connective tissue
inherited as an autosomal dominant condition of variable expression
and its classical form comprises of skeletal, cardiovascular and
ocular abnormalities. It is attributed as a defect in the mutation in the
fibrillin gene. The syndrome has a wide range of expression from
mild to the severe forms. Sometimes the symptoms are so mild that
only few of the symptoms occur. In most cases, the disease
progresses with age and symptoms of Marfans Syndrome become
noticeable as changes in the connective tissue occur. Most of the
reported cases so far are associated with cardiovascular
abnormalities. We report a case of Marfans Syndrome associated
with epilepsy.
Key words: Marfans Syndrome, Arachnodactly, Blue sclera,
Epilepsy.
1
Department of Oral
Medicine and
Radiology, AB Shetty
Memorial Institute of
Dental Sciences,Nitte
University.
Mangalore / India
İletişim / Corresponding
Author:
Deepa Dsouza
Department of Oral
Medicine and Radiology
AB Shetty Memorial
Institute of dental
Sciences, Nitte
University
Mangalore / India
Phone number:
+918951362580
Email:
dr.deepasdsouza@live.c
om
Received / Başvuru
Tarihi:
28-07-2011
Accepted / Kabul
Tarihi:
20-02-2012

Çağdaş Tıp Dergisi 2012; 2(1): 33-37 Dsouza ve ark.
Introduction:
Marfans syndrome is a variable
autosomal dominant disorder of the connective
tissue.
1
It was first described by Marfan in
1896.
2
Approximately 85% of the case are
familial with the rest arising as a result of new
mutations.
3
Mutations in the FBN1 is associated
with a broad spectrum of phenotypes.
4
Marfans
syndrome may affect cardiovascular, central
nervous system, musculoskeletal, pulmonary,
ocular and integumentary systems.
5
The
diagnosis is commonly considered in young
patients with tall, thin body habitus, long limbs,
arachnodactly, pectus deformity and scoliosis.
Other findings are high arched palate with
crowding of teeth.
1
According to Ghents
classification 1 major and 4 minor features
supports the diagnosis in this case.
4
We report a
case of Marfans syndrome with similar features
and CNS findings.
Case report:
A 14-year-old female patient reported
to the department with a complaint of forward
placement of teeth. She was aware of the
condition following the eruption of the
permanent teeth causing severe esthetic
discomfort. Patient presented with a history of
epileptic seizures that were occasional and
transient. The patient was on an ayurvedic
medication for the same for epilepsy and had
no episodes of seizures since the past one year.
She also reported of a history of myopia (near
sightedness) which was corrected with
spectacles. She was wearing them since young
ages.
The patient was well oriented with
time, place and was cooperative during the
clinical examination. On examination, skeletal
findings like tall stature with slender limbs,
long narrow face (leptoproscopic), long narrow
head (dolicocephalic), thin body habitus with
increased arm span to height ratio, long slender
limbs, long fingers and toes (arachnodactly),
Figure 1a –Photograph showing Tall stature with
thin body habitus
Figure 1b- Long slender upper limbs and fingers
deformities of the chest (pectus carinatum),
abnormal curvature of the spine (scoliosis),
joint hypermobility, flat feet, downward
slanting palpebral fissures, malar hypoplaisa
were observed (Fig. 1a & 1b). Walker sign
(wrist) and Steinberg sign (thumb) was positive
(Fig 2a & 2b).
Figure 2a- Photograph showing wrist sign (Walker
Sign positive)

Journal of Contemporary Medicine 2012; 2(1): 33-37 Dsouza et al.
35
Figure 2b- Photograph showing Steinberg’s sign
Ocular findings under slit lamp
examination performed by a qualified
opthamologist revealed ectopia lentis
(subluxation of the lens) that was bilaterally
symmetrical and upwards, blue sclera (Fig. 3).
Figure 3 –Photograph showing blue sclera
Qualified cardiologist evaluated the
patient and a electrocardiography was carried
out which revealed no abnormalities. Oral
findings were microstomia, incompetent lips,
proclination of upper anteriors with high arched
palate (Fig.4).
Figure 4-Photograph showing high arched palate.
Orthopantomogram revealed the
presence of impacted canine in the maxilla and
dilacerated premolar in the mandible (Fig 5).
Based on these clinical presentations and
opinions from the medical professional a
provisional diagnosis of Marfans syndrome
associated with epilepsy was constituted. Oral
prophylaxis was carried out and orthodontic
treatment was initiated for the correction of
malocclusion.
Figure 5-Orthopantomogram showing impacted
canine in the maxilla and dilacerated premolar in the
mandible.
Discussion:
Marfans syndrome (MFS) is a variable
autosomal dominant disorder of the connective
tissue.
1
It was first discovered by Antonie
Marfan (French pediatrician) in the year 1896
as dolicostenomelia which means long limbs. It
was first seen in a 5-year-old patient, later it
was referred as MFS.
2
It is caused due to
mutation in the FBN1 gene located on
chromosome 15, band q15-q23 which codes for
the connective tissue fibrillin.
3
The incidence is
1 in 9800 births and 27% of cases occur due to
new mutations.
1
Mutations in FBN1 gene have
been associated with a broad spectrum of
phenotypes.
4
More than 135 new mutations
have been identified in the FBN1 gene.
5
Neonatal MFS constitutes 14% of the total
cases. The presentation in adults and
adolescents is well known.
6
Fibrillin-1 forms an
important component of microfibrillin. It is a
glycoprotein synthesized as a precursor that is
processed and secured in the extracellular
matrix (ECM). It polymerises to form
microfibrillin and helps to stabilize the latent
transforming growth factor-β binding protein
(LTBPs) in the ECM. LTBPs hold the TGF-β
(TGF- β) in inactive stage. A failure of
interaction between fibrillin-1 and LTBPs may
result in excess of TGF-β signaling. Most
Fibrillin-1 mutations are a missence, suggesting
a dominant negative effect on the microfibrillar
assembly.
1
Fibrillin-1 is essential for the
formation of extracellular matrix and
maintainance of elastin fibres. Elastin fibres are
found in the aorta, ligaments and ciliary zones
of the eyes and these areas are the most
affected.
7

Çağdaş Tıp Dergisi 2012; 2(1): 33-37 Dsouza ve ark.
Table:1 Criteria for Diagnosis of Marfan Syndrome(1996
Ghent classification system)
System
Affected
Major Criteria
Minor
Criteria
Cardiovascular
system
Dilatation of the
ascending aorta, with or
without aortic
regurgitation, involving
at least the sinuses of
Valsalva
Dissection of the
descending aorta
Dilatation or
dissection of
the descending
thoracic or
abdominal
aorta before 50
years of age
Dilatation of a
main
pulmonary
artery before
40 years of age
Mitral valve
prolapse with
or without
mitral
valve
regurgitation
Calcification
of the mitral
annulus before
40 years of age
Musculoskeletal
system
Scoliosis with a
curvature greater than
20°
or spondylolisthesis
Pectus carinatum
Pectus excavatum
requiring surgery
Acetabular protrusion
Reduced upper-to-
lower segment ratio, or
arm span-to-height ratio
greater than
1.05
Wrist and thumb signs
Reduced extension of
the elbow (_170°)
Medial displacement of
the medial malleolus
causing pes planus
Pectus
excavatum of
moderate
severity
Joint
hypermobility
Highly arched
palate with
crowding of
teeth
Abnormal
facial
appearance
(dolichocephal
y,
malar
hypoplasia,
enophthalmos,
retrognathism,
down-slanting
palpebral
fissures)
Central nervous
system
Lumbosacral dural
ectasia at CT or MR
imaging
None
Pulmonary
system
None
Spontaneous
pneumothorax
Apical blebs
Ocular system
Ectopia lentis
Abnormal flat
cornea
Increased axial
length of the
globe
Hypoplastic
iris or
hypoplastic
ciliary
muscle causing
decreased
miosis
Integumentary
system
None
Striae
atrophicae
Recurrent or
incisional
hernia
Abnormalities in protein synthesis causes a
myriad of distinct clinical problems of which
the musculoskeletal, cardiac and ocular
problems predominate.
8
There is a striking
intrafamilial and individual variability in the
clinical manifestations of MFS, variability that
is suggestive of some phenotype and genotype
correlation.
7
The severe end of the clinical
contiguum is defined as a rapidly progressive
form that is present at birth and is associated
with functional impairment and death in early
childhood.
4
Diagnosis is further complicated by
the age dependency of symptoms and signs,
which leads to a changing clinical picture in
younger patients who are suspected with the
disorder but do not fulfill the clinical diagnostic
criteria should be offered repeated clinical
evaluations.
9
The diagnosis of MFS was based
on the Berlin classification (1986) and was later
revised as the Ghent classification in 1996. The
presence of 2 major features and 1 minor
feature or the presence of 1 major and 4 minor
features supports the diagnosis of MFS because
of the presence of ectopia lentis and
musculoskeletal abnormalities. (Table:1)
7
This
case report satisfies the criteria required to
support the diagnosis of MFS. Rare instance of
neurological findings such as epilepsy have
been reported.
8
On rare events association of
mental retardation and lumbosacral
meningocele has also been reported.
9
Vascular
abnormalities can be a cause of cerebral and
spinal ischeamia/haemorrage events involving
the brain/spinal cord are estimated in 10-20% of
the patients in MFS.
12
Since there is the risk of
the offsprings inherting the genetic
predisposition to the disorder parents should be
counseled well in advance.
4
New method of
diagnosis can include investigation of mutation
analysis (FBN1 gene).
As of 1995, the life
expectancy of those affected with the syndrome
has increased to 72 years, up from 48 years in
1972, which is attributed to the new surgical
techniques, improved diagnosis and newer
techniques of medical treatment.
13
Advancement of research in MFS holds support
of further improvements in the future.

Journal of Contemporary Medicine 2012; 2(1): 33-37 Dsouza et al.
37
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