Apert Syndrome Versus Crouzon Syndrome: about Two Cases
Mailongo Tsimi C1*, Ombwa Eballe A2,
Hoffman W3, Bella Assumpta4
1Yaoundé Central Hospital
2Douala LaquintinieHospital
3BongoloHospital
4Yaoundé Obstetrical, Gynaecological and Paediatric Hospital
*Corresponding author: Caroline Mvilongo Tsimi, Depatment of
Ophthalmologist, Yaoundé Central Hospital, Yaoundé, Cameroon, France. Tel:+
00237 99 32 47 96/ 00237703100; Email: carolinemvilongo@yahoo.fr
Introduction
Both Apert-Crouzon and Crouzon syndromes are characterized by a
prematured-craniosyntosis, patients suffering from apert syndrome have also
hands and feet syndactyly. They are autosomal dominant genetic disorder
associated in most case with mutation in the genes of the Fibroblast Growth
Factor Receptor 2 (FGFR 2) [1]. It is a rare syndrome with multiple deformities
(1/100,000 births in France and 15/100.000 births in USA), occurring mostly in
Caucasians, Asiatic and Afro-Americans without sex discrimination [2]. We are
describing two cases of craniostenosis, one apert syndrome and one Crouzon
focussing on the following aspects: clinical presentation, variants, evolution
and therapeutic issues in our context.
Medical Observation
Case 1
Child X, 13 year old, presented with several months complaints
of eyes pain, impaired vision and right eye lacrimation. No treatment has been
taken.
From his past medical history, he has facial dysmorphia since
childbirth associated with a cerebral palsy. There
Is neither family history of similar case nor in breeding.
The eye examination showed: bilateral exophthalmia with
hypertelorism and lagophtalmia, impaired right eye vision to light. In the left
eye the acuity = 6/36 and IOP= 29mmHg.Hertel RE = 33mm and LE = 27mm with exotropia.
Slit lamp examination of anterior and posterior segments
revealed:
1.
Right eye: conjunctival hyperaemia associated with a central
corneal yellow infiltrate of about 7-8mm up taking fluoresce in; narrow and
quiet anterior chamber; iris and pupil were not seen. The posterior segment was
not accessible.
2.
Left eye: Conjunctival hyperaemia associated with a superficial
punctuates keratitis. The funduscopic examination was blurred.
In total, she had a keratitis due to exposure and a strabismus
(Figure 1).
We had the following findings on general examination: a
brachycephaly, a flattened occiput, an anterior bulging forehead, depressed
nasal bridge with a tiny nose, dental retrognathism and malposition (Figure 2).
This is associated to the 2nd, 3rd, and 4th fingers
bilateral and symmetric syndactyly (Figure 3), to the four toes syndactyly and
stocky big toes (Figure 4), To a gait with widened base and mental debility (Figure
5).
No limbs and brain CT scan were done.
The treatment consisted of: artificial tears, antibiotics for
the ocular dryness and inflammation. Neurosurgery intervention was not done;
the patient was referred to an orthopaedist for managing the syndactylies.
Case 2
KM, 13 year old, referred from the neurosurgeon for ophthalmic
management of a Crouzon syndrome.
From his past medical history, he has facial dysmorphia since
childbirth. There is neither family history of similar case nor inbreeding. He
had a normal vaginal delivery in term.
The eye examination showed: corrected visual acuity of 10/10 in
the right eye and 7/10 in the left eye, bilateral exophthalmia, Hertel LE =
25mm, irreducible, painless and axile with lagophtalmia and superficial
punctuate keratitis, alternating exotropia of 45 DP (figure 6).
The posterior segment revealed:
1.
Right eye: a pupil with C/D at 0.2 with temporal pallor and neat
edge.
2.
Left eye: a pupil with C/D at 0.2 with temporal pallor,
surrounding papillary atrophy and a neat edge.
We had the following findings on general examination: a facial
dystrophy with a hypertelorbistism, an exorbitism and an inverted dental
articulate. The treatment consisted on artificial tears and bilateral lateral
tarsorrhaphy.
Discussion and Literature Review
Our observation illustrates both Apart and Crouzon syndromes
evocative clinical features. Apart syndrome has been described by Dr Eugene
Apart in 1906. It is a multiple malformations syndrome characterized by: a
craniosynostosis (premature fusion of skull bones); craniofacial disorders
(hypoplasia of middle floor); symmetric fingers and sometime feet syndactyly
(fusion of fingers) giving mittens fingers appearance; mental retardation at
variable degree; often associated with cardiac and visceral disorders [3-5].
In 1912, Crouzon described a syndrome characterized by
craniosynostosis, hypertelorism, exophthalmia, parrot-beaked nose, short upper
lip, hypo plastic maxilla and a relative mandibular prognathism. Cranial
malformation depends on the order and rate or progression of suturalsynostosis.
Brachycephaly is the most commonly observed, but scaphocephaly and
trigonocephaly also are described. A shallow orbit is an essential diagnostic
feature. Ocular proptosis is a consequence and results in a high frequency of
conjunctivitis [1].
Epidemiology
Apert syndrome is a rare disease (occurs approximately in
1/160,000 birth) belongs to the group of craniosynostosis, where it represents
only 4-5% of causes [3].
Genetic
The craniosynostoses are a heterogeneous group of syndromes
characterized by a pre- mature sutural fusion that may occur alone or together
with other anomalies. More than 70 syndromes are described. Apert and Crouzon
syndromes are well-known craniosynostosis [1]. In the more common
craniosynostosis syndrome like syndromes of Crouzon, Pfeiffer, Jackson-Weiss,
and Apert, mutations were found in the gene coding for Fibroblast Growth Factor
Receptor (FGFR) 2. Less frequently, mutations are observed in FGFR1 and FGFR3
in some cases of Crouzon and Pfeiffer syndrome. The mutations identified in
FGFR2 are located in exons 5 and 7 of the gene that code for immunoglobulin
(Ig)-like chain III and the region linking Ig II and Ig III of the receptor
[2].
Age
Our two patients were seen at in advanced age of 13 year old. According
to David et al in 2012, craniosynostosis are predominant in male, 56% and 66.7%
in Crouzon and Apert syndromes respectively [6]. We have reported one case of
Apert syndrome in a female.
Clinical Presentation
There are significant differences in the ocular manifestations
of Apert and Crouzon syndromes. In Crouzon syndrome, ocular proptosis is
primarily caused by retrusion of the lateral and inferior orbital margins with
a very short orbital floor. In Apert syndrome, the eye globe actually protrudes
in relation to the cranial base and to the orbit, probably resulting from
marked protrusion of the lateral orbital wall. The implications account for
some of the differences encountered. Asymmetry is associated with Apert
syndrome frequently. Exotropia is found in Crouzon syndrome, whereas the V
pattern is more characteristic in Apert syndrome with divergent up gaze and
esotropicdowngaze [7].
Our patient suffering from Apert syndrome had exposure keratitis
and central corneal ulcer due to the exopthalmia.
According to Gray et al in 2005, ophthalmic sequelae of Crouzon
syndrome are numerous. The most common cause of visual impairment was
amblyopia, which was present in 21% of patients, followed by optic atrophy in
7%. Ametropia occurred in 77% of patients. Strabismus occurred in 39% of
patients and exposure keratopathy was observed in 15% of patients [8].
Khong et al in 2006 found 54% of patients suffering from visual
impairment in a cohort of Apert syndrome. The most common cause was amblyopia,
with a prevalence of 35%. Optic atrophy caused visual impairment in 5% of
patients and corneal scarring in 8%. Sixty-three percent of patients had
strabismus with more esotropia than exotropia. Ametropia was found in 69% of
patients [9]. From those two studies, the main complications of Apert and
Crouzon syndromes are first the amblyopia followed by optic atrophy, strabismus
and exposure keratitis. Our two patients suffered from alternate exotropia and
exposure keratitis due to the exophthalmia.
Other ophthalmic disorders are described such as lachrymal
apparatus malfunction, lack of extra ocular muscles, ocular albinism,
keratoconus, congenital glaucoma and cataract [9].
In sporadic cases, the prenatal diagnosis of Apert syndrome on
ultrasound is difficult. It is always late during in pregnancy. The 3D
ultrasound is useful. The use of molecular biology of foetal sample is
essential in diagnosis. The molecular biology techniques used are those
highlighting point mutations, PCR followed by ultrasound, enzymatic digestion
or sequencing [3].
Treatment: The craniosynostosis are surgically treated. It is a
corrective neurosurgery done soon, around three months old, aiming to stem or
to decrease the orbital and ocular disorders which can threat the vision and
binocular balance.
Prognosis
The severity in the management of Apert syndrome is due to the
co-existence of multiple malformations with a risk of chronic intracranial
hypertension responsible of blindness and mental retardation [10,11].
Conclusion
Apert and Crouzon syndromes are well known craniosynostosis. In
the last 10 years, several studies have been done to provide a better
comprehension of the etiology and pathogenesis of these syndromes. Both have an
autosomal dominant mode of transmission and a mutation in the gene encoding for
the FGFR2 as the cause in most patients.
Early detection to reduce amblyopia by correction of refractive
errors, timely treatment of strabismus, and patching should be a priority for
ophthalmologists and a goal of the craniofacial teams managing patients with
Crouzon and Apert syndrome. Optic atrophy and exposure keratitis remains an
important cause of visual impairment in these patients before
decompressivecraniectomy. The management has to be multidisciplinary and done
early.
Figure 1: Exposurekeratitis and strabismus.
Figure 2: Maxillar Hypoplasia and mandibular prognathism.
Figure 3: Fingerssyndactyly.
Figure 4: Fingers and feet syndactyly.
Figure 5: Typical facial features in Apert syndrome.
Figure 6: Bilateral exosphthalmia, telorbitism and extropia.
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