Congenital lens coloboma and associated pathologies

Coloboma of the lens is characterized by notching of the equator of the lens. The cause of the condition is faulty development of the zonule. The lens deprived of its normal pull in the defective region is thicker and more spherical as if there were no loss of its substance. We report five cases of lens coloboma and localized zonular defect without any associated systemic anomalies. One case included retinal detachment; another included an iris coloboma; and a third included iris, choroid and optic disk colobomas and retinal detachment with lens coloboma. The remaining two cases were without associated ocular anomalies. The pathogenic mechanisms and relationship of this defect with the differentiation of the tertiary vitreous and development of the zonule is discussed. The defect most likely occurs in the third to fourth months of gestation during differentiation of the tertiary vitreous in response to toxic, inflammatory or genetic factors.     

显微手术在眼睑缺损修复与重建中的应用

目的对78例不同类型眼睑缺损修复与重建回顾性总结,了解显微手术应用的必要性。方法43例采用眼科显微手术器械,部分在手术显微镜下操作。35例采用普通手术器械在肉眼下操作。结果显微手术组创面全部I期愈合,眼睑外形良好。普通手术组1例延期愈合,7例遗留肉眼可见细小瘢痕。两组癫痕形成率P＜0．01。结论证明了显微手术在眼睑缺损的修复与重建中必要和可行。     

Congenital anomalies of the optic nerve

Congenital optic nerve head anomalies are a group of structural malformations of the optic nerve head and surrounding tissues, which may cause congenital visual impairment and blindness. Each entity in this group of optic nerve anomalies has individually become more prevalent as our ability to differentiate between them has improved due to better characterization of cases. Access to better medical technology (e.g., neuroimaging and genetic analysis advances in recent years) has helped to expand our knowledge of these abnormalities. However, visual impairment may not be the only problem in these patients, some of these entities will be related to ophthalmologic, neurologic and systemic features that will help the physician to identify and predict possible outcomes in these patients, which sometimes may be life-threatening. Herein we present helpful hints, associations and management (when plausible) for them.     

A 14q distal chromoanagenesis elucidated by whole genome sequencing

Chromoanagenesis represents an extreme form of genomic rearrangements involving multiple breaks occurring on a single or multiple chromosomes. It has been recently described in both acquired and rare constitutional genetic disorders. Constitutional chromoanagenesis events could lead to abnormal phenotypes including developmental delay and congenital anomalies, and have also been implicated in some specific syndromic disorders. We report the case of a girl presenting with growth retardation, hypotonia, microcephaly, dysmorphic features, coloboma, and hypoplastic corpus callosum. Karyotype showed a de novo structurally abnormal chromosome 14q31qter region. Molecular characterization using SNP-array revealed a complex unbalanced rearrangement in 14q31.1-q32.2, on the paternal chromosome 14, including thirteen interstitial deletions ranging from 33 kb to 1.56 Mb in size, with a total of 4.1 Mb in size, thus suggesting that a single event like chromoanagenesis occurred. To our knowledge, this is one of the first case of 14q distal deletion due to a germline chromoanagenesis. Genome sequencing allowed the characterization of 50 breakpoints, leading to interruption of 10 genes including YY1 which fit with the patient's phenotype. This precise genotyping of breaking junction allowed better definition of genotype-phenotype correlations.     

Novel BRPF1 mutation in a boy with intellectual disability,coloboma, facial nerve palsy and hypoplasia of the corpus callosum

Mutations in the chromatin regulator gene BRPF1 were recently associated with the Intellectual Developmental Disorder With Dysmorphic Facies And Ptosis (IDDDFP). Up till now, clinical data of 22 patients are reported. Besides intellectual disability (ID), ptosis and blepharophimosis are frequent findings, with refraction problems, amblyopia and strabism as other reported ophthalmological features. Animal studies indicate BRPF1 as an important mediator in brain development. However, only 5 of 22 previously reported patients show structural brain abnormalities.We report on an additional patient harboring a novel de novo nonsense mutation p.(Glu219*) in BRPF1. He presented with ID, bilateral iris colobomas, facial nerve palsy and severe hypoplasia of the corpus callosum. Our findings support previous findings of brain abnormalities in BRPF1-mutations and indicates coloboma and facial nerve palsy as possible additional features of IDDDFP syndrome.     

Sequence variations in TENM3 gene causing eye anomalies with intellectual disability: Expanding the phenotypic spectrum

Microphthalmia, anophthalmia are the malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball. Coloboma of iris is associated with many of the cases. Here, we report a propositus with eye anomalies and intellectual disability associated with TENM3 pathogenic variations identified by exome sequencing and confirms intellectual disability as a phenotype associated with TENM3 variations. This child was compound heterozygote [NM_001080477.3(TENM3):c.4046C?>?G; p.(Ala1349Gly) and NM_001080477.3(TENM3): c.7687C?>?T; p.(Arg2563Trp)] for the missense likely pathogenic sequence variations in TENM3 gene. To our knowledge only three patients till now have been reported to have TENM3 pathogenic variations in association with microphthalmia, two siblings without developmental delay and third with developmental delay. This report supports the association of TENM3 variations with colobomatous microphthalmia and expands the phenotypic spectrum associated with pathogenic variations in this gene.     

先天性黄斑缺损1例

先天性黄斑缺损是指黄斑区视网膜和脉络膜的先天性发育异常,是最严重影响中心视力的眼底先天异常,病因不明,临床较少见.近期我院诊断1例,报告如下. 1 临床资料 患者,女,41岁,主因自幼双眼视物不清,于2011年12月16日来我院就诊.     

Low-level complex mosaic with multiple cell lines affecting the 18q21.31q21.32 region in a patient with de novo 18q terminal deletion

We describe a 5-year-old girl who was diagnosed at birth with 18q de novo homogeneous deletion at G-banding karyotype. Her clinical condition, characterized by hypotonia, psychomotor retardation, short stature, deafness secondary to bilateral atresia of the external auditory canals, was in agreement with the 18q deletion syndrome though presence of coloboma of a single eye only suggested a mosaic condition as an unusual sign. By combining multiple technologies including array-CGH, FISH, and WGS, we found that the terminal deletion 18q21.32q23 (21 Mb) was in segmental mosaicism of the proximal region 18q21.31q21.32 (2.7 Mb), which showed a variable number of copies: one, two, or three, in 7, 41 and 55% of the cells respectively. Breakpoint junction analysis demonstrated the presence of an inv-dup del (18q) with a disomic segment of 4.7 kb between the inverted and non-inverted copies of the duplicated region 18q21.31q21.32. From these results, we propose that all three types of abnormal chr18 (the inv-dup del and the two 18q terminal deletions of different sizes) arisen from breaks in a dicentric mirror chromosome 18q, either in more than one embryo cell or from subsequent breaking-fusion-bridge cycles. The duplication region was with identical polymorphisms as in all non-recurrent inv-dup del rearrangements though, in contrast with most of them, the 18q abnormality was of maternal origin. Taking into account that distal 18q deletions are not rarely associated with inv-dup del(18q) cell lines, and that the non-disjunction of chromosome 18 takes place especially at maternal meiosis II rather than meiosis I, multiple rescue events starting from trisomic zygotes could be considered alternative to the postmitotic ones. From the clinical point of view, our case, as well as those of del(18q) in mosaic with the dic(18q), shows that the final phenotype is the sum of the different cell lines that acted on embryonic development with signs typical of both the 18q deletion syndrome and trisomy 18. Asymmetrical malformations, such as coloboma of the iris only in the right eye, confirm the underlying mosaicism regardless of whether it is still detectable in the blood.     

Lateral frontal encephalocele associated with dysplasia of orbit,eyeball, and eyelid

A case is reported of a right lateral frontal encephalocele without communication with the midline structures and in concurrence with dysplasia of the orbit, eyeball, and eyelid.     

Is There an Association between Maternal Carbamazepine Use during Pregnancy and Eye Malformations in the Child?

PURPOSE: To check for an association between carbamazepine (CBZ) use by the mother during pregnancy and congenital eye malformations (i.e., anophthalmia, microphthalmia, and coloboma) in the child, as suggested by Sutcliffe et al. (1998), who reported four cases. METHODS: We checked all the cases with these eye malformations for CBZ use by the mother in the EUROCAT Northern Netherlands dataset, which registers infants with congenital malformations and records possible teratogenic exposures (including medication taken by the mother). We also reviewed 13 studies in the literature. RESULTS: The EUROCAT dataset recorded 77 cases of anophthalmia, microphthalmia, or coloboma, but none with prenatal exposure to CBZ. Prenatal CBZ exposure was recorded in seven other cases without congenital eye malformation. Large studies in the literature on the teratogenic effects of CBZ (and other antiepileptic drugs), including data from the MADRE database, revealed no association between these congenital eye malformations and prenatal CBZ exposure. One case reported bilateral anophthalmia and other congenital anomalies after prenatal exposure to CBZ in combination with vigabatrin and dexamethasone. CONCLUSIONS: Our data do not support Sutcliffe's suggestion that prenatal CBZ exposure may result in congenital eye malformations. However, despite the large population represented, both the low birth prevalence of these congenital eye malformations and the low prevalence of CBZ exposure during pregnancy make it difficult to exclude an increased relative risk. The many large prospective and retrospective studies in the literature seem to agree with our findings, although there is still uncertainty about the teratogenic effect of CBZ in polytherapy.