OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.
China ; Coloboma ; Eye Proteins ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics* ; Mutation ; Osteochondrodysplasias ; Pedigree ; Pregnancy ; Prenatal Diagnosis

Cat eye syndrome (CES) is a very rare chromosomal syndrome characterized by various malformations such as anal atresia, preauricular malformation, coloboma of the iris, and congenial heart and renal defects. This genetic disorder is caused by partial duplication of chromosome 22, mostly as a result of a supernumerary isodicentric marker chromosome idic(22)(q11.2). Various congenital abnormalities and extreme phenotypic variability in CES patients have been reported, which have made prenatal diagnosis of CES difficult. We report the first case diagnosed with CES prenatally by multiplex ligation-dependent probe amplification in a woman who was referred to our hospital, for a fetus presenting with heart anomaly.
Animals ; Anus, Imperforate ; Cats* ; Chromosomes, Human, Pair 22* ; Coloboma ; Congenital Abnormalities ; Female ; Fetus ; Genetic Markers ; Heart ; Humans ; Iris ; Multiplex Polymerase Chain Reaction* ; Prenatal Diagnosis*

Bilateral choanal atresia is a rare disorder characterized by bilateral obstruction of the posterior end of the nasal cavity. It can be present in isolation or associated with multiple disorders such as coloboma, heart defect, choanal atresia, retarded growth, genital hypoplasia, ear abnormalities (CHARGE) syndrome. Because congenital bilateral choanal atresia presents as respiratory distress at birth, immediate diagnosis and adequate treatment is required. Traditionally, using stents was a part of the postoperative treatment to provide a low rate of restenosis but recently it is controversial. Currently nasal endoscopic approach is mainly used with or without stenting. We report a case of CHARGE syndrome with bilateral choanal atresia treated by transnasal endoscopic approach without stenting.
CHARGE Syndrome ; Choanal Atresia* ; Coloboma ; Diagnosis ; Ear ; Heart ; Nasal Cavity ; Parturition ; Stents*

CHARGE syndrome has been estimated to occur in 1:10,000 births worldwide and shows various clinical manifestations. It is a genetic disorder characterized by a specific and a recognizable pattern of anomalies. The major clinical features are ocular coloboma, heart malformations, atresia of the choanae, growth retardation, genital hypoplasia, and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene, located on chromosome 8q12.1, causes CHARGE syndrome. The CHD7 protein is an adenosine triphosphate (ATP)-dependent chromatin remodeling protein. A total of 67% of patients clinically diagnosed with CHARGE syndrome have CHD7 mutations. Five hundred twenty-eight pathogenic and unique CHD7 alterations have been identified so far. We describe a patient with a CHARGE syndrome diagnosis who carried a novel de novo mutation, a c.3896T>C (p. leu1299Pro) missense mutation, in the CHD7 gene. This finding will provide more information for genetic counseling and expand our understanding of the pathogenesis and development of CHARGE syndrome.
Adenosine Triphosphate ; CHARGE Syndrome* ; Chromatin Assembly and Disassembly ; Coloboma ; Diagnosis ; Ear ; Genetic Counseling ; Heart ; Humans ; Mutation, Missense ; Nasopharynx ; Parturition

We report a case of recurrent choroidal neovascularization (CNV) in an eye with chorioretinal coloboma. A 36-year-old woman presented complaining of decreased visual acuity (VA) in her left eye. Best corrected visual acuity (BCVA) was 20/200 and iris coloboma was observed. Funduscopy and fluorescein angiography (FA) showed CNV in the superior extrafoveal region with chorioretinal coloboma reaching just inferior to the optic disc. No other cause for CNV was observed except for the chorioretinal coloboma. BCVA improved to 20/30 after laser photocoagulation. She revisited our clinic for deteriorating VA (20/400) in the same eye 3 years after treatment. Funduscopy and FA demonstrated recurrent CNV with subfoveal hemorrhage. Photodynamic therapy (PDT) was followed by three consecutive intravitreal bevacizumab injections (IVB) for the subfoveally-located CNV. However, the CNV persisted with the appearance of a fresh subretinal hemorrhage. Additional PDT was combined with IVB on the same day 6 months after the initial PDT. The CNV regressed 3 months after treatment and has not recurred as of 8 months after the last treatment. The patient's BCVA improved to 20/60. This case suggests that PDT combined with IVB can be an alternative treatment for the management of recurrent CNV after laser photocoagulation in eyes with chorioretinal coloboma.
Adult ; Angiogenesis Inhibitors/administration & dosage ; Antibodies, Monoclonal/administration & dosage ; Choroid Diseases/*complications/drug therapy/surgery ; Choroidal Neovascularization/diagnosis/*etiology/physiopathology ; Coloboma/*complications/drug therapy/surgery ; Female ; Fluorescein Angiography ; Fundus Oculi ; Humans ; Intravitreal Injections ; Laser Coagulation ; Photochemotherapy ; Recurrence ; Visual Acuity

An 18-year-old man presented with poor vision in both eyes that had been present since birth. Central corneal opacity and inferior peripheral sclerocornea with iridocorneal adhesion were observed upon anterior segment examination of the left eye. A coloboma of the iris was observed in the patient's right eye, which manifested as a small notch in the inferior pupillary margin and cataract. Fundus examination of the right eye showed a large inferior chorioretinal coloboma involving the optic disc and macula. It is essential to examine the fundus in detail, if possible, in cases of Peters' anomaly, because these patients may have congenital anomalies such as chorioretinal coloboma.
*Abnormalities, Multiple ; Adolescent ; Anterior Eye Segment/abnormalities ; Choroid/*abnormalities ; Coloboma/*diagnosis ; Corneal Opacity/*diagnosis ; Diagnosis, Differential ; Eye Abnormalities/*diagnosis ; Humans ; Male ; Microscopy, Acoustic ; Optic Nerve/abnormalities ; Retina/*abnormalities

An 18-year-old man presented with poor vision in both eyes that had been present since birth. Central corneal opacity and inferior peripheral sclerocornea with iridocorneal adhesion were observed upon anterior segment examination of the left eye. A coloboma of the iris was observed in the patient's right eye, which manifested as a small notch in the inferior pupillary margin and cataract. Fundus examination of the right eye showed a large inferior chorioretinal coloboma involving the optic disc and macula. It is essential to examine the fundus in detail, if possible, in cases of Peters' anomaly, because these patients may have congenital anomalies such as chorioretinal coloboma.
*Abnormalities, Multiple ; Adolescent ; Anterior Eye Segment/abnormalities ; Choroid/*abnormalities ; Coloboma/*diagnosis ; Corneal Opacity/*diagnosis ; Diagnosis, Differential ; Eye Abnormalities/*diagnosis ; Humans ; Male ; Microscopy, Acoustic ; Optic Nerve/abnormalities ; Retina/*abnormalities

The 22q11 region has been implicated in chromosomal rearrangements that result in altered gene dosage, leading to three different congenital malformation syndromes: DiGeorge syndrome, cat-eye syndrome (CES), and der(22) syndrome. Although DiGeorge syndrome is a common genomic disorder on 22q11, CES is quite rare, and there has been no report of Korean CES cases with molecular cytogenetic confirmation. In this study, we present the phenotypic and genetic characteristics of a 3-month-old boy with CES. Clinical findings included micropthalmia, multiple colobomata, and renal and genital anomalies. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, which was identified as a bisatellited and isodicentric chromosome derived from an acrocentric chromosome. The results of array comparative genomic hybridization and fluorescence in situ hybridization studies confirmed the karyotype as 47,XY,+mar.ish idic(22)(q11.1) (D22S43+).arr 22q11.1(15,500,000-15,900,000)x4, resulting in a partial tetrasomy of 22q11.1. To the best of our knowledge, this is the first report in Korea of CES confirmed by cytogenetic and molecular cytogenetic analyses.
Abnormalities, Multiple/genetics ; Aneuploidy ; Chromosome Disorders/diagnosis/genetics ; *Chromosomes, Human, Pair 22/genetics ; Coloboma/genetics ; Craniofacial Abnormalities/genetics ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; Phenotype ; *Tetrasomy ; Ultrasonography, Prenatal

Achondroplasia is a congenital disorder resulting from a specific disturbance in endochondral bone formation. The ophthalmic features reportedly associated with achondroplasia are telecanthus, exotropia, inferior oblique overaction, angle anomalies and cone-rod dystrophy. This is first report of chorioretinal coloboma in achondroplasia. An 8-year-old female was diagnosed with a developmental delay, known as achondroplasia, seven months after birth. Upon her initial visit, visual acuity was 0.3 in both eyes. The patient had telecanthus but normal ocular motility. Findings were normal upon anterior segment examination. Fundus examination of both eyes revealed about 1,500 microm sized chorioretinal coloboma inferior to the optic nerve head. Upon fluorescent angiography, there was chorioretinal coloboma without any other lesions. Afterward, there was no change in the fundus lesion, and best corrected visual acuity was 0.6 in both eyes. Chorioretinal coloboma is associated with choroidal and retinal detachment. As chorioretinal coloboma and achondroplasia are developmental disorders in the embryonic stage, early detection and regular ophthalmologic examination would be essential in patients with achondroplasia.
Achondroplasia/*complications/diagnosis ; Child ; Choroid/*abnormalities ; Choroid Diseases/*complications/diagnosis ; Coloboma/*complications/diagnosis ; Female ; Humans ; Ophthalmoscopes ; Tomography, Optical Coherence ; Visual Acuity

We report a rare case of retinal detachment in colobomatous macrophthalmos with microcornea syndrome. A 25-year-old female who had suffered from poor vision in her left eye since early childhood and high myopia in her right eye (-11 D) visited our clinic because of a sudden deterioration of vision. Examination of the anterior segment showed microcornea with coloboma of the inferior pupil margin in the left iris. Fundus examination of the left eye revealed an inferior choroidal coloboma extending from the optic disc and macula. The patient also had total bullous retinal detachment. Pars plana vitrectomy with silicone oil tamponade was performed, and the retina was reattached. In the very rare condition of colobomatous macropthalmos with microcornea, retinal detachment may develop. Pars plana vitrectomy with additional silicone oil tamponade may be performed to treat this condition.
Adult ; Choroid/*abnormalities ; Coloboma/*complications/diagnosis ; Cornea/*abnormalities ; Female ; Follow-Up Studies ; Humans ; Retinal Detachment/diagnosis/*etiology/surgery ; Syndrome ; Vitrectomy/methods