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\begin{document}

\title{A case of PAX6 gene mutation with bilateral Peters anomaly}



\author[1]{Wei He}%
\author[1]{Lu Chang}%
\author[1]{Dong Huang}%
\author[1]{Qin Jiang}%
\affil[1]{Affiliation not available}%


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  \date{May 17, 2024}


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\begin{abstract}
The patient in this case can walk alone and take care of himself.
Therefore through surgical separation and removal of the cloudy lens,
the establishment of a visual pathway can help improve the children's
vision and improve their quality of life.%
\end{abstract}%



\sloppy


A case of PAX6 gene mutation with bilateral Peters anomaly

Wei He Lu Chang Xudong Huang Yaqin Jiang

Department of Ophthalmology, Weifang Eye Hospital, Weifang, Shandong, PR

China

Correspondence: Yaqin Jiang, Weifang Eye Hospital, Weifang, Shandong

Province, China, email: \emph{jyqopht@163.com}

Abstract

Rationale: Peters anomaly as a kind of anterior segment diseases was
rarely reported, we reported a case of PAX6 gene mutation with bilateral
Peters anomaly treated with cataract surgery.

Patient concerns: A 5-year-old male was referred to our ophthalmologic
hospital, because of bilateral corneal opacity since birth. Anterior
segment photograph showed the central corneal opacity with
neovascularization in the right eye, which peripheral cornea was clear
and peripheral pupillary membrane could be found. The obscured opacified
lens adhesion to the porcelain white cornea could be found in the left
eye. A heterozygous PAX6 gene mutation c.357+1G\textgreater{}C leads to
splicing mutations in amino acids.

Diagnosis: Peters anomaly Type 2

treatment: Cataract extraction combined with anterior vitrectomy in the
double eyes in different time.

Lessons: The patient in this case was in stable condition after surgery,
can walk alone and take care of himself. The patient and family members
are satisfied with the treatment scheme. Therefore through surgical
separation and removal of the cloudy lens, the establishment of a visual
pathway can help improve the children's vision and improve their quality
of life.

Keywords: Peters anomaly; PAX6 gene;

Key Clinical Message

A 5-year-old male was referred to our ophthalmologic hospital, A
heterozygous PAX6 gene mutation c.357+1G\textgreater{}C leads to
splicing mutations in amino acids. Peters anomaly Type 2 was made.
Cataract extraction combined with anterior vitrectomy surgery was mede
in the double eyes in different time.

Peters anomaly(PA) is a form of anterior segment malformation,
characterized by corneal opacity and keratolenticular adhesion with
associated defects in the posterior layers of the cornea. PAX6 gene
mutation may be related to anterior segment abnormity such as PA{[}1{]}.
Congenital corneal opacity as a serious vision-threatening disease,
leads to severe visual impairment. The PA has been classified to Type 1,
Type 2 and peters anomaly syndrome, according to different clinical
manifestation. There are different surgical approaches have been taken
to treat different PA. The clinical diagnosis and management of Peters
anomaly type II in a Chinese child has been reported in our
presentation.

A 5-year-old male was referred to our ophthalmologic hospital, because
of bilateral corneal opacity since birth. Written informed consent was
obtained from the patient's parents to create this report. He was
delivered normally by the mother and there was no the experience of
oxygen uptake. Both parents are in good health. There was no congenital
abnormities nor similar ocular disorders was revealed in family members.
The patient underwent fundamental ophthalmic examinations. His vision
was hand movement in double eyes, so he can not walk independently. The
intraocular pressure measured with I-care tonometer (Finland Oy,
Helsinki, Finland) was respectively 21.3 mmHg(1mmHg= 0.1333224kpa) and
32 mmHg in the right and left eye. Anterior segment
photograph(Haag-Streit, Bern, Switzerland) (Figure 1A) showed the
central corneal opacity with neovascularization in the right eye, which
peripheral cornea was clear and peripheral pupillary membrane could be
found. The obscured opacified lens adhesion to the porcelain white
cornea could be found in the left eye (Figure 1B). The retina and optic
disc could not be seen. Binocular nystagmus. Axis oculi measured with
ophthalmic A - scan ultrasonography was 21.83mm and 23.44mm in the right
and left eye. B-scan ultrasonography(Figure 2) showed a normal posterior
segment in the double eyes. Anterior segment OCT(Figure 3) showed lens
echo enhanced and adhere to the cornea. Genital, skeletal and cardiac
abnormalities didn't present through physical examinations. We did the
genetic testing for the patient and his parents, by extracting the
peripheral blood for genetic testing and found mutations in the PAX6
gene. Individual exons of the PAX6 gene was amplified by polymerase
chain reaction(PCR). A heterozygous PAX6 gene mutation
c.357+1G\textgreater{}C leads to splicing mutations in amino
acids(Figure 4). However, PAX6 gene of his parents was normal, so it was
spontaneous mutation. The diagnosis of Peters anomaly Type 2 was made.
Immediate cataract extraction combined with anterior vitrectomy in the
right eye was advised, and the patient's parents consented our surgical
scheme. Under general anesthesia, a conjunctival peritomy was created at
the area of maximally clear peripheral cornea. A limbal incision was
fashioned directly at corneal limbus. Viscoelastic was injected to the
anterior chamber to create space between the cornea and lens. Then
Inserted anterior chamber perfusion. During the operation, we found that
the lens was not fully developed and optoaxial lens was opacity. 23G
vitrectomy removed the lens and anterior vitreum(Figure 5A). The corneal
incision was then closed with 10--0 Vicryl suture. The first day after
surgery, the intraocular pressure measured with I-care tonometer was
16.5 and 35mmHg in the right and left eye. The viusal acuity was
FC/40cm. The right eye was treated with anti-inflammation and mydriasis
therapy. 1 week later, the same operation was performed to the left eye.
Because the cornea was porcelain, 23G vitrectomy removed the lens with
the assistance of 23G cold light illuminator (Figure 5B). During the
operation, we found that the lens was not fully developed and optoaxial
lens was opacity, indistinctly. Separation of adhesive opacified lens
and anterior vitreum was performed. The first day after surgery of left
eye, there was no obvious abnormality in slit-lamp examination(Figure
6). Anterior segment OCT(Figure 7) and B-scan ultrasonography(Figure 8)
showed a normal anterior and posterior segment in the double eyes.
Viusal acuity was 0.01 and hand movement in the right eye and left eye.
The intraocular pressure measured with I-care tonometer was 19.5mmHg and
18.2mmHg in the right and left eye. Topical antibiotics and
corticosteroid drops were applied after the procedure and were gradually
reduced.

PA as a rare congenital dysgenesis of the anterior segment diseases, was
first described in 1906 by Dr Alfred Peters{[}2{]} PA is a polygenic
hereditary disease caused by abnormal neural crest cell migrate to
cornea during development. This abnormal migration has been proved to be
related to mutations in pax6, pitx2, foxe3 and cyplbl genes. PAX6
mutation also has been proved as a Genetic Factor in one Peters'anomaly
patient of Tetsuyuki Yasuda research{[}3{]}. Alough mutation of the PAX6
gene maybe related to Peters'anomaly, Calvas et al. investigated the
PAX6 coding region in four patients with Peters' anomaly but without any
mutations{[}4{]}. We found exon 6 mutations in pax6 gene that were
previously confirmed to be aniridia related{[}5{]}. The etiology of PA
mainly includes intrauterine infection, incomplete separation of lens
vesicles from the epidermal embryoblast and developmental disorder of
nerve cells{[}6{]}. Therefore, the environment and genes maybe both as
pathogenic factors{[}7{]}. The clinical sign of Type II PA is
keratoleukoma with cataract or adhesion of corneal and lens{[}8{]}.
Clinical ophthalmic characteristic led us to classify our patient as
Type II PA. The management of PA depends on the corneal status and
accompanied anomalies. Haruna Yoshikawa considers it is likely that in
eyes with the less-severe type of PA without glaucoma, corneal opacity
can be expected to decrease during the first several years from birth.
However, patients with cataract and glaucoma should be given surgical
intervention to prevent sensory amblyopia and irreversible glaucoma
damages. In this case presentation, we successfully removed the
cataract. Because the corneal of left eye was porcelain, 23G vitrectomy
removed the lens with the assistance of 23G cold light illuminator to
overcome the difficulty of the lack of transparent cornea. Due to
abnormal ocular tissue development and visual impairment, patients with
Peters abnormality have greater difficulty in refractive correction in
the evaluation of therapeutic effects and postoperative refractive
parameter measurement. The patient in this case was in stable condition
after surgery, can walk alone and take care of himself. The patient and
family members are satisfied with the treatment scheme. Therefore
through surgical separation and removal of the cloudy lens, the
establishment of a visual pathway can help improve the children's vision
and improve their quality of life.

Figure 1A:Anterior segment photograph showed the central corneal opacity
with neovascularization in the right eye. Figure 1B: The obscured
opacified lens adhesion to the porcelain white cornea could be found in
the left eye.

Figure2: B-scan ultrasonography showed normal posterior segment in the
double eyes

Figure3 Anterior segment OCT showed lens echo enhanced and adhere to the
cornea

Figure4: A heterozygous PAX6 gene mutation c.357+1G\textgreater{}C leads
to splicing mutations in amino acids, PAX6 gene of his parents was
normal.

Figure5A: 23G vitrectomy removed the lens and anterior vitreum in the
right eye.

Figure5B: 23G vitrectomy removed the lens with the assistance of 23G
cold light illuminator in the left eye.

Figure6: Anterior OCT showed the normal anterior segment in the double
eyes

Figure7: B-scan ultrasonography showed a normal posterior segment in the
double eyes

There is no conflicts between the authors

There is no funding supportment

Acknowledgments

The authors are grateful to the patient and his parents.

Author contributions

Data curation: Wei He, Lu Chang.

Formal analysis: Wei He.

Investigation: Wei He, Lu Chang, Xudong Huang, Yaqin Jiang.

Project administration: Yaqin Jiang.

Resources: Yaqin Jiang.

Supervision: Xudong Huang, Yaqin Jiang.

Validation: Wei He, Lu Chang, Xudong Huang, Yaqin Jiang.

Writing - original draft: Wei He.

Writing -- review and editing: Lu Chang, Xudong Huang, Yaqin Jiang

References

{[}1{]} Hanson IM, Fletcher JM, Jordan T, et al. Mutations at the PAX6
locus are found in heterogeneous anterior segment malformations
including Peters' anomaly.~\emph{Nat Genet} . 1994;6(2):168-173.
doi:10.1038/ng0294-168.

{[}2{]} Hanson IM, Fletcher JM, Jordan T, et al. Mutations at the PAX6
locus are found in heterogeneous anterior segment malformations
including Peters'anomaly. Nat Genet. 1994;6(2):168--173.

{[}3{]} Yasuda T, Kajimoto Y, Fujitani Y, et al. PAX6 mutation as a
genetic factor common to aniridia and glucose intolerance. Diabetes.
2002;51(1):224-230. doi:10.2337/diabetes.51.1.224.

{[}4{]} Calvas P, Rozet J-M, Gerber S, Munnich A, Kaplan J: Novel Pax6
home-odomain mutations in congenital aniridia and identification of a
new alternative splicing of Pax6 mRNA (Abstract). Am J Hum Genet 59
(Suppl.):A394, 1996.

{[}5{]} Calvas P, Rozet J-M, Gerber S, Munnich A, Kaplan J: Novel Pax6
home-odomain mutations in congenital aniridia and identification of a
new alternative splicing of Pax6 mRNA (Abstract). Am J Hum Genet 59
(Suppl.):A394, 1996.

{[}6{]} Bhandari R, Ferri S, Whittaker B, et a1. Peters anomaly: review
of the literature. Cornea. 2011; 30: 939-944.

{[}7{]} Lakshmi N, Maina Pk. Microphthalmia and microcornea: in
congenital cytomegalovirus. Indian J Ophthalmol. 2009;57(4):323.

{[}8{]} Harissi-Dagher M, Colby K. Anterior segment dysgenesis: Peters
anomaly and sclerocornea. Int Ophthalmol Clin. 2008;48(2):35-42.

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