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A practical guide to
the management of
anophthalmia and
microphthalmia
NK Ragge, ID Subak-Sharpe and JRO Collin
Abstract
Congenital anophthalmia and microphthalmia
are rare developmental defects of the globe.
They often arise in conjunction with other
ocular defects such as coloboma and orbital
cyst. They may also be part of more
generalised syndromes, such as CHARGE
syndrome. Anophthalmia, microphthalmia,
and coloboma are likely to be caused by
disturbances of the morphogenetic pathway
that controls eye development, either as a
result of primary genetic defect, or external
gestational factors, including infection or
drugs that can influence the smooth processes
of morphogenesis.
The ophthalmologist is often the primary carer
for children with anophthalmia and
microphthalmia, and as such can coordinate
the multidisciplinary input needed to offer
optimal care for these individuals, including
vision and family support services. They are
able to assess the vision and maximise the
visual potential of the child and they can also
ensure that the cosmetic and social impact of
anophthalmia or microphthalmia is minimised
by starting socket expansion or referring to a
specialist oculoplastics and prosthetics unit.
A coordinated approach with paediatrics is
necessary to manage any associated
conditions. Genetic diagnosis and
investigations can greatly assist in providing a
diagnosis and informed genetic counselling.
Eye (2007) 21, 1290–1300; doi:10.1038/sj.eye.6702858
Keywords: anophthalmia; microphthalmia;
coloboma; cyst; prosthesis; hydrophilic
expander
Background
Congenital anophthalmia and microphthalmia
are rare defects of the globe resulting from
abnormalities in the development of the
primary optic vesicle. Anophthalmia has an
incidence of 0.18–0.4/10 000 births
1,2
and
microphthalmia around 1.5–19/10 000 births.
2,3
The term anophthalmia is used where there is
no visible ocular remnant. However, ultrasound
often reveals a buried microphthalmic remnant
or cyst. Microphthalmia refers to an eye with
reduced volume and may be associated with
coloboma or with an orbital cyst. It may usefully
be subdivided into microanterior segment
(when the overall axial length may be normal or
even increased), and microposterior segment,
since each of these may have a different
underlying aetiology. There is a spectrum of
disease that exists between these conditions.
Both anophthalmia and microphthalmia may be
unilateral or bilateral, and over 50% may be
associated with systemic abnormalities
4
(and Ragge, unpublished data). In the case of
unilateral anophthalmia or microphthalmia,
there may be developmental anomalies of the
other eye, including coloboma, lens, and optic
nerve abnormalities.
5,6
Assessment in the neonatal unit
The management of a child presenting with
suspected anophthalmia or microphthalmia
benefits from the coordinated involvement of
a multidisciplinary team of health care
professionals. The initial assessment is likely to
be carried out by a paediatrician and/or
paediatric ophthalmologist in the neonatal
period. Early examination by an
ophthalmologist is crucial and will include both
a diagnostic and visual assessment, leading to
an early management plan. The initial meeting
with the parents allows the ophthalmologist to
explain both the condition and the likely
management plan. The parents are likely to be
deeply traumatised early on, especially if the
findings were not predicted prenatally, and a
Received: 7 March 2007
Accepted: 4 April 2007
Department of
Ophthalmology, Moorfields
Eye Hospital, London, UK
Correspondence: NK Ragge,
Department of
Ophthalmology,
Moorfields Eye Hospital,
City Road,
London EC1 2PD, UK
Tel: þ 020 7 566 2577;
Fax: þ 020 7 566 2972.
E-mail: nicky.ragge@
dpag.ox.ac.uk
Eye (2007) 21, 1290–1300
& 2007 Nature Publishing Group All rights reserved 0950-222X/07 $30.00
www.nature.com/eye
CAMBRIDGE OPHTHALMOLOGY SYMPOSIUM
discussion of diagnosis, if known, and likely aetiology
and investigations is helpful at this stage.
An early paediatric assessment involves a full
examination of the whole child to search for any
associated systemic abnormalities. The child may already
be known to have significant other medical problems,
requiring active management even at this stage.
Particular attention is focused upon the face, including
ear and palate, the cardiac system, genital anomalies,
feeding difficulties, which might indicate oesophageal
abnormality, and metabolic disturbances, which may
indicate pituitary underaction. A management or referral
plan is then made depending on any systemic
abnormalities identified.
Assessment in the eye clinic
As soon as possible in the first few weeks after birth, the
child will be assessed in the paediatric eye clinic. If there
are severe ocular anomalies, the assessment would be
best carried out in the first 2 weeks of life. The history
will focus on trying to make a diagnosis by establishing
any other ocular or systemic features, and identifying
aetiological factors, in particular any relevant gestational
factors or family history of other ocular or systemic
abnormalities. The diagnostic assessment confirms
anophthalmia, microphthalmia, coloboma, orbital cyst,
or other associated ocular pathology. It is important to
examine both eyes since in cases of unilateral
anophthalmia or microphthalmia the fellow eye may
show other, more subtle, abnormalities such as
coloboma, optic nerve hypoplasia, retinal dystrophy, or
cataract. An ultrasound of the eye and orbit can be useful
to determine the internal structure of the eye, the
presence of an ocular remnant or cyst, where this is not
immediately visible, and to determine axial length in
cases of microphthalmia.
Vision is assessed using early paediatric vision tests,
and electrodiagnostics if necessary. A flash visual evoked
potential (VEP) will establish if any vision is present in
cases of apparent anophthalmia or severe
microphthalmia; a pattern VEP will both establish a level
of acuity and detect any optic nerve dysfunction, and an
electroretinogram will identify if there is retinal
dysfunction.
Children with even quite severe microphthalmia may
have some vision and it is important to establish this
early on, especially in bilateral cases, as it will guide the
approach to socket expansion (Figure 4).
Investigations and screening
The child will need several investigations in addition to
orbital ultrasound and electrodiagnostic testing. Since
many conditions that affect ocular development also
affect brain development, it is important to arrange
imaging of the brain, particularly looking at midline
structures, the hippocampus and periventricular
structures. Magnetic resonance imaging (MRI) is
preferable to computed tomography scanning since there
is higher resolution of the structures of interest and no
radiation exposure (important in conditions such as
Gorlin syndrome). Renal ultrasonography is also
recommended given the association between eye and
renal anomalies. The paediatrician is also likely to have
screened for intrauterine infections. Congenital rubella
has long been associated with microphthalmia
7
and it
would be important to exclude this given an appropriate
history during pregnancy. There have also been case
reports of microphthalmia associated with other
intrauterine infections such as varicella, Toxoplasma
gondii, herpes simplex virus, and cytomegalovirus.
8–11
In addition, early assessment of hearing is particularly
important to allow prompt intervention in the case of
abnormality.
Examination of other family members for related
ocular pathology such as anophthalmia or
microphthalmia, anterior segment malformation,
glaucoma, coloboma, retinal dystrophy, and optic nerve
hypoplasia is important since this may provide a clue to
likely diagnosis or inheritance pattern. Genetics
assessment will include chromosome analysis and
testing of particular genes. In our centre, we routinely
carry out fine resolution chromosome analysis and
screening of a wide range of genes on a research basis or
in collaboration with various diagnostic laboratories.
Management
The management of children with anophthalmia or
microphthalmia is often best achieved through a shared
care approach between the local ophthalmic and
paediatric services and a specialist centre. To maximise
the visual potential of the child glasses are prescribed for
any significant refractive error and, in the case of
children with only one, sighted eye for protection.
Socket expansion
Early socket expansion is important to minimise facial
deformity and can be started very soon after birth in
cases of anophthalmia or severe microphthalmia. This is
best carried out in a specialist unit with a good ocular
prosthetic service available. The normal eye in a child at
birth is approximately 70% of its adult size. By contrast,
the face even by 3 months is only 40% of adult face size.
There is, however, rapid growth of the face and by
2 years it is 70% of adult size and by 5.5 years 90% of
A practical guide
NK Ragge et al
1291
Eye
adult size.
12
Normal facial and orbital development is
affected by reduction in ocular volume and in cases of
anophthalmia and moderate or severe microphthalmia
there is often underdevelopment of the bony orbit, the
eyelids, and the fornices. Without intervention, the socket
remains underdeveloped and the ability to wear a
prosthesis in later life is compromised. In unilateral cases
the asymmetry becomes more pronounced as the child
grows. The cosmetic deformity that can ensue without
intervention can lead to marked difficulties with social
interaction. With appropriate treatment the cosmetic
outcome is greatly improved (Figures 1–7).
Progressive growth of the socket can be facilitated by
adding volume to the socket using socket expanders.
Traditionally, this involved frequent visits to hospital for
sequential socket expansion using progressively larger
acrylic shapes with or without moulding of the socket
under anaesthesia. However, more recently the use of
hydrophilic expanders has allowed a relatively
non-invasive start to the expansion process and a
reduction in the number of initial visits to hospital
needed to produce satisfactory socket expansion.
13,14
Hydrophilic expanders, for example those manufactured
by Acri.Tec
&
, are available in several sizes and are placed,
or sutured, in the socket, along with topical
preservative-free antibiotic drops. The lids are then
closed over the expander with a temporary tarsorrhaphy,
secured either by suturing or with histoacryl glue. In our
experience, glue is easier, can be performed in clinic
under topical anaesthetic and leads to very few
complications. A painted prosthesis is then introduced as
appropriate (Figure 5). This is usually increased in size at
regular intervals until symmetry is achieved or no more
expansion is possible. In some cases, additional
reconstruction, such as a primary orbital implant in
anophthalmic, or severely microphthalmic, non-seeing
eyes, may be necessary. This allows use of a smaller
painted prosthesis, which is easier to insert and remove.
The parents and eventually the child are taught how to
manage the prosthesis, although frequent checks by an
ocularist will continue to be needed.
In the case of microphthalmic eyes, especially where
there is vision, the situation is a little different and
management varies according to the centre. Where the
microphthalmic eye has an axial length of less than
16 mm (Collin, unpublished observation), it is unlikely to
promote normal orbital growth alone and it is therefore
necessary to increase the socket volume early on to
prevent asymmetry becoming more pronounced as the
child grows. In this situation, a purpose-made cosmetic
shell can be fitted over the microphthalmic eye or ocular
remnant to promote orbital growth. Clear shapes will
need to be fitted initially in the case of eyes with a
positive VEP, or with a good-sized eye with a cornea. In
bilateral cases, this will need to continue throughout life
(Figure 6). Since hydrophilic expanders are translucent,
they can be fitted in front of severely microphthalmic
eyes with light perception without the fear of blocking
out the vision. However, they cannot be used with
moderately microphthalmic eyes since these need clear
moulded shapes in front of them to avoid damage to the
underlying eye (Figure 1).
Figure 1 Girl with left microphthalmia (a) before socket expansion with cosmetic shell (b) view of microphthalmic eye (c) appearance
wearing cosmetic shell over L microphthalmic eye.
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Eye
Some centres will remove a non-seeing eye, and use a
dermis fat graft/ball implant at an early stage. Our
preference, however, is to preserve the microphthalmic
Figure 2 Girl with L anophthalmia undergoing sequential socket expansion using solid shapes. Note initial slanting of L brow, which
signifies a smaller L orbit, and subsequent symmetry of brows. (a) 5 months old, (b) 15 months old, (c) 21 months old, (d) 2 years
2 months old, (e) 3 years 10 months, (f) 5 years 3 months.
Figure 3 Two boys with R anophthalmia (a and c) as young
babies before socket expansion using solid shapes and (b and d)
demonstrating symmetrical socket appearance.
Figure 4 Girl with R extreme microphthalmia and left
microphthalmia and coloboma wearing a right prosthesis to
match the microphthalmic left eye.
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NK Ragge et al
1293
Eye
eye even if there is no visual potential. The advantages of
this approach are that the microphthalmic eye is likely to
provide some stimulus to palpebral aperture and socket
growth, especially where the microphthalmia is only
mild or where there is an associated orbital cyst and it
avoids the need for early invasive surgery with all its
accompanying risks.
15
A clear conformer is created and
inserted, allowing the health of the underlying
microphthalmic eye to be observed. Subsequently, when
the fit is satisfactory, a hand-painted prosthesis can be
made. In mild or moderate microphthalmia, this needs
good clearance over the cornea. In severe unilateral
microphthalmia, it will fill the available socket space.
When the axial length of the eye is over 16 mm, or if
there is a large cyst present, the fitting of such a
prosthesis is more optional, as orbital growth is more
likely to be normal (although this should be kept under
observation). The timing is then governed by social and
aesthetic need, for example a good time to introduce a
prosthesis might be just before the child starts school.
The question of when to change a clear prosthesis over
a unilateral microphthalmic eye with some vision
Figure 5 The results of socket expansion using hydrophilic expanders are seen in this girl with L anophthalmia (a) with hydrophilic
expander in situ and (b) with first painted prosthesis.
Figure 6 (a) Girl with bilateral severe microphthalmia and no perception of light wearing bilateral prostheses. (b) Boy with clinical
anophthalmia, but with light perception wearing clear prostheses.
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NK Ragge et al
1294
Eye
(such as light perception) for a painted prosthesis is
difficult. A clear prosthesis allows the maximum visual
potential of the microphthalmic eye to be reached and
the health of the underlying eye to be checked. However,
once a stable situation is reached, the vision is unlikely to
be lost even if the microphthalmic eye is covered, and
better cosmesis, and probably better vision and stability
of the good eye will be achieved if a painted prosthesis is
fitted (Figure 1).
16
For patients with anophthalmia or microphthalmia
and a large orbital cyst, gradual socket enlargement can
usually be achieved using the natural expansion
produced by the cyst (Figure 7). The parents may need
gentle reassurance that this is the best policy as initially
the appearances may be unsightly. Occasionally, the cyst
may need to be drained because it has grown too rapidly.
However, caution should be observed with this, since
there is often a direct connection with the eye itself, and
the cyst usually refills in any case. We find that by
2–4 years of age the sockets of most affected children
have developed sufficiently for the orbital cyst to be
removed. Before this surgery we perform an MRI of the
orbits to assess the cyst size, and any potential
connection to the brain. After cyst excision and, if
necessary, orbital implant, the patients receive a
temporary and subsequently custom made ocular
prosthesis (Figure 7).
Long-term management
After the initial socket expansion over the first 5 years of
life, the prosthesis and the socket will require review at
least yearly. Microphthalmic eyes may develop angle
closure glaucoma, which may cause loss of what vision
does exist and can also cause pain.
17
Children with
chorioretinal coloboma and their parents should be
aware of the increased risk of retinal detachment and
receive instructions for prompt attendance in the case of
any alteration in vision.
18
Glasses are prescribed for
refractive error, protection, and sometimes for providing
lenses to minimise cosmetic defect (such as plus lenses to
increase the size of a microphthalmic eye or prisms to
equalise a height discrepancy).
Paediatric and genetic follow-up
Associated systemic abnormalities may have very major
implications for the child and so may need considerable
input from general or specialist paediatric services. In the
case of bilateral anophthalmia or severe microphthalmia
with no light perception, there may be a reversal of sleep
pattern. In this situation, melatonin supplements at night
may be very helpful to establish a regular nocturnal sleep
pattern. Growth assessment is important since there may
be associated pituitary abnormalities. Developmental
assessment by a paediatrician skilled in assessing
children with visual problems will detect any early
difficulties, but can also provide welcome reassurance for
parents, since there is a variance in developmental
progress of visually impaired children compared with
their sighted peers (www.earlysupport.org.uk) (see Box 1
and Box 2).
It is important to reach an overall diagnosis if possible,
since this will direct future management. The parents are
Figure 7 Girl with L microphthalmia and cyst (a) cyst in situ acting as socket expander, (b) post-removal preserving the
microphthalmic eye and wearing L painted prosthesis.
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Eye
usually keen to understand the nature of the condition,
and a combined approach from paediatrics,
ophthalmology, and genetics will help to achieve this.
The parents may wish to receive genetic counselling
regarding the risks of another child being affected,
although in some cases, they may wish to wait. The high
incidence of de novo mutations, mosaicism, and variable
penetrance, combined with a large overlap in phenotype
even among those with the same genetic mutation,
makes genetic counselling very complex,
19,20
and we
would always advise the ophthalmologist involved in
the care of these children to involve an ophthalmic or
medical geneticist.
Vision and family support
It is very important that any visually impaired child
receives early help from vision support services. The
Box 2 Three major questions most parents want to know
1 What can be done to help my child see?
To a large extent this will depend on whether the condition is
unilateral or bilateral. Electrodiagnostic testing will help to
determine visual potential. This is followed by early
refraction. Where there is potential for vision, clear socket
shapes can be used to expand the socket.
2 What can be done cosmetically?
The key to this is early socket expansion, with either
sequential socket shapes or a hydrophilic expander. Ocular
prostheses and if necessary, orbital implants can give
excellent results. Further lid surgery may also be needed.
Orbital cysts are usually excised when the socket is fully
developed, often around 2–4 years of age.
3 Why did it happen and will it happen again in my family?
This can be addressed best by genetic testing and
counselling, and enrolment in a research study for testing
new genes if desired.
Box 1 The role of the ophthalmologist in management of
suspected anophthalmia/microphthalmia
1 Confirmation of the diagnosis of anophthalmia,
microphthalmia, coloboma, or orbital cyst. Ultrasonography
may be very helpful in this.
2 Visual assessment, including electrodiagnostics if possible.
3 Referral to a paediatrician to assess other congenital
abnormalities, growth and development, in particular
looking for signs of the common systemic associations for
example cleft lip/palate, heart defects, kidney and pituitary
anomalies, developmental delay.
4 Minimise cosmetic and social impact of anophthalmia or
microphthalmia by commencing socket expansion or
referring to a specialist unit for socket expansion.
5 Once the diagnosis is confirmed, and at the parents’ wishes,
referral to a specialist for genetics counselling.
Table 1 Selected genes and syndromes associated with eye malformations
Name of Gene Name of syndrome Ocular manifestations Systemic manifestations Inheritance Refs
SOX2 3q26.3-q27 SOX2 anophthalmia
syndrome, some cases of
AEG (anophthalmia-
oesophageal-genital)
syndrome
Anophthalmia,
microphthalmia, cataract,
retinal dystrophy
Hypothalamic –
pituitary abnormalities,
growth failure, genital
tract malformation,
developmental delay,
seizures, oesophageal
atresia
Autosomal
dominant –
usually de novo
mutation
22–24,
26, 31
OTX2
14q21-14q22
Anophthalmia,
microphthalmia, coloboma,
microcornea, cataract,
retinal dystrophy, optic
nerve hypoplasia
Agenesis of the corpus
callosum, developmental
delay
Autosomal
dominant
20
PAX2
10q24.3-25q.1
Renal-coloboma
syndrome or
Papillorenal syndrome
Coloboma, microphthalmia Renal hypoplasia Autosomal
dominant
32
PAX6 11p13 Aniridia, Peters’ anomaly,
foveal hypoplasia,
keratopathy
Abnormalities of
pituitary, pancreatic, and
brain development
Autosomal
dominant,
compound
heterozygotes
have
anophthalmia
25, 26,
33
CHD7 8q12.1 CHARGE syndrome Microphthalmia, coloboma Heart defects, choanal
atresia, retarded growth
and development,
genital hypoplasia, ear
anomalies, and deafness
Autosomal
dominant
27, 28
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Eye
Table 1 (Continued )
Name of Gene Name of syndrome Ocular manifestations Systemic manifestations Inheritance Refs
PTCH 9q22.3 Basal cell naevus
syndrome/Gorlin’s
syndrome
Microphthalmia, coloboma,
cyst
Palmer pits,
medulloblastoma basal
cell carcinoma
Autosomal
dominant
29
SHH 7q36 Holoprosencephaly-3
(HPE3)
Cyclopia, coloboma,
hypotelorism
Preaxial polydactyly,
cleft lip and palate
Autosomal
dominant
30, 34
CHX10 14q24.3 Anophthalmia,
microphthalmia, coloboma,
cataract, iris abnormalities
Autosomal
recessive
19, 21
FOXC1 6p25 Axenfeld–Rieger
syndrome
Iris hypoplasia,
iridogoniodysgenesis,
glaucoma
Dental abnormalities,
midface abnormalities
Autosomal
dominant
35
HCCS Xp22 Microphthalmia with
linear skin defects
Microphthalmia,
sclerocornea
Linear skin defects,
agenesis of corpus
callosum
X-linked
dominant
36
BRIP1 17q22 Fanconi anaemia Microphthalmia Bone marrow failure,
breast cancer, growth
retardation, cafe
´
-au-lait
spots, hearing loss,
thumb and kidney
abnormalities
Autosomal
dominant
37
DPD 1p22 Microphthalmia, coloboma,
nystagmus
Epilepsy, mental
retardation, motor
retardation
Autosomal
recessive
38
SIX3 2p21 Holoprosencephaly 2 Cyclopia, Microphthalmia,
coloboma
hypotelorism,
microcephaly,
craniofacial anormalities
Autosomal
dominant
39
SIX6 14q23 Microphthalmia, cataract,
nystagmus
Pituitary abnormalities Autosomal
dominant
40, 41
PITX2 4p25 Rieger syndrome Iris hypoplasia,
iridogoniodysgenesis,
glaucoma
Maxillary hypoplasia,
dental abnormalities,
excess periumbilical skin
Autosomal
dominant
42
POMT1 9q34.1 Walker-Warburg
syndrome
Microphthalmia, cataract,
anterior chamber
abnormalities, retinal
dysplasia and detachment,
persistent hyperplastic
primary vitreous, coloboma,
optic nerve hypoplasia
Developmental delay,
muscular dystrophy,
hydrocephalus, agyria,
epilepsy
Autosomal
recessive
43
BCOR Xq27-q28 Oculofaciocardiodental
syndrome
Microphthalmia, congenital
cataract
Mental retardation, heart
defects, dental and facial
abnormalities
X-linked recessive 44
RX 18q21.3 Anophthalmia,
microphthalmia,
sclerocornea
Autosomal
recessive
45
FRAS1 4q21 Fraser Syndrome Microphthalmia,
cryptophthalmos
Genital and kidney
abnormalities, finger
webbing
Autosomal
recessive
46
FREM2 13q13.3 Fraser Syndrome Microphthalmia,
cryptophthalmos
Genital and kidney
abnormalities, finger
webbing
Autosomal
recessive
47
HESX1
3p21.2-p21.1
Septo-optic dysplasia Optic nerve hypoplasia Agenesis of the corpus
callosum,
panhypopituitarism, and
absent septum
pellucidum
Autosomal
dominant
48
MAF 16q22-q23 Cataract, anterior segment
dysgenesis, coloboma
Nephritic syndrome Autosomal
dominant
49
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Eye
child may qualify for a Certificate of Visual Impairment,
which may help to expedite some of the services and
financial support available. There are publications, such
as ‘Show me what my child can see’ (available from the
Wolfson Centre, Mecklenburg Sq, London WC1N 2AP)
which can help parents to interact with their babies if
visually impaired. Early intervention undoubtedly
makes a huge difference to the overall development of
the child and the emotional well-being of the family.
In addition to the more widely known organisations
for the visually impaired, there are two British charities,
the Eyeless Trust (www.eyeless.org.uk) and MACS
(Microphthalmic and Anophthalmic Children’s Society,
www.macs.org.uk) who can offer specialist advice and
family support to these children and their families. Other
charities that can be very helpful to these children
include VICTA (Visually Impaired Children Taking
Action, www.victa.org.uk), VISION and LOOK (The
National Federation of Families with Visually Impaired
Children, www.look-uk.org).
Aetiology and genetics
The development of the eye is highly complex. It is
determined by sequential and coordinated expression of
eye development genes within the developing tissues.
Although some individuals with anophthalmia or
microphthalmia have relatives with other eye
malformations, the frequent lack of clear Mendelian
inheritance in these conditions has made identifying the
genes for eye development very challenging. However,
using a variety of techniques, some genes involved in
anophthalmia or microphthalmia have now been
identified (see Table 1). These include genes principally
involved in ocular development, such as CHX10, many of
which are involved in the development of substructures
within the eye
19,21
and genes that are involved in eye and
brain development including SOX2, OTX2, and
PAX6.
20,22–26
Several syndromic genes are involved in
developing other organs in addition to the eye, including
CHD7, the gene for CHARGE syndrome
27,28
and PTCH,
the gene for Gorlin syndrome.
29
There is a complex
interplay between the different eye development gene
pathways, which allows their expression to be finely
regulated
5,27,30
and begins to explain why there is such an
overlap of the phenotypes associated with mutations of
each gene.
Acknowledgements
Nicola Ragge is a Senior Surgical Scientist supported
through an Academy of Medical Sciences and Health
Foundation Fellowship. www.acmedsci.ac.uk;
www.health.org.uk. We are extremely grateful to many
who support the specialist anophthalmia and
microphthalmia services, in particular our consultant
colleagues, Mr Yassir Abou-Rayyah, Dr Alison Salt; the
prosthetists: Nigel Sapp, David Carpenter and Peter
Coggin; Marie Restori for ultrasound, Medical Illustration,
Chris Timms and all the orthoptists, the paediatric nurses,
Christine Ennals, family support services, Dr Graham
Holder Electrodiagnostics Dept., optometry services, and
Celestria Bell for family liaison. We acknowledge with
deepest gratitude the generous support from the Eyeless
Trust, VICTA and the Polak Trust. Above all, we wish to
dedicate this article to the individuals with anophthalmia
and microphthalmia and their families.
References
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2 Kallen B, Tornqvist K. The epidemiology of anophthalmia
and microphthalmia in Sweden. Eur J Epidemiol 2005; 20(4):
345–350.
3 Morrison D, Fitzpatrick D, Hanson I, Williamson K, van
Heyningen V, Fleck B et al. National study of
microphthalmia, anophthalmia and coloboma (MAC) in
Scotland; Investigation of genetic aetiology. J Med Genet
2002; 39(1): 16–22.
4 Tucker S, Jones B, Collin JRO. Systemic anomalies in 77
patients with congenital anophthalmos or microphthalmos.
Eye 1996; 10: 310–314.
5 Gregory-Evans CY, Williams MJ, Halford S, Gregory-Evans
K. Ocular coloboma: a reassessment in the age of molecular
neuroscience. J Med Genet 2004; 41: 881–891.
Table 1 (Continued )
Name of Gene Name of syndrome Ocular manifestations Systemic manifestations Inheritance Refs
RAB3GAP
2q21.3
Warburg Micro
Syndrome
Microphthalmia,
microcornea, optic atrophy,
cataract
Microcephaly, mental
retardation, hypoplasia
of corpus callosum,
hypothalamic
hypogenitalism
Autosomal
recessive
50
For a more complete list of conditions associated with coloboma, the reader is referred to the reviews by Gregory-Evans et al. and Chang et al.
5,6
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