A Korean case of Cornelia de Lange syndrome

PURPOSE: Cornelia de Lange syndrome is a rare disease showing characteristic facial appearance, developmental delay, growth retardation, low birth weight, skeletal formation anomaly, hirsutism and various ophthalmologic problems. METHODS: We experienced a case of an 18-year-old female with Cornelia de Lange syndrome showing superficial keratitis with entropion, ptosis, high myopia, lacrimal cutaneous fistula and characteristic facial appearance. She was born with low birth weight, operated for cleft palate and diagnosed with ventricular septal defect. In addition, she showed psychological lag and developmental impairment. RESULTS: We performed entropion correction surgery, administered medical therapy for superficial keratitis and prescribed glasses for her myopia. CONCLUSIONS: This is the first case report on the successful correction of entropion with Cornelia de Lange syndrome in Korea.     

Ophthalmologic findings in the Cornelia de Lange Syndrome.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a disorder caused in many patients by a mutation in the NIPBL gene with a dominant pattern of inheritance characterized by mental retardation, prenatal and postnatal growth retardation, upper-limb abnormalities, and characteristic facies. Few data exist concerning the ophthalmic findings in this syndrome. METHODS: One hundred twenty individuals with CdLS underwent ophthalmic examination to ascertain the relative frequencies of oculofacial and ophthalmic abnormalities. RESULTS: We confirmed the frequent findings of synophrys (99%), long lashes (99%), hypertrichosis of the brows (96%), ptosis (44%), epiphora (22%), nasolacrimal duct obstruction (16%), blepharitis (25%), and myopia (58%). In addition, we found peripapillary pigment (83%), and microcornea (21%), which have infrequently been mentioned in the literature. CONCLUSION: Patients with CdLS can have multiple eye problems. Many of these problems can be readily treated, including myopia, blepharitis, nasolacrimal duct obstruction, and ptosis. Early examination is recommended for all children known or suspected to have CdLS.     

Ophthalmologic findings in the Cornelia de Lange syndrome

Background: Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by multisystem abnormalities, including distinct ophthalmologic findings. In recent years, advances in molecular genetics have begun to provide new insight into the characterization of these clinical features and the genetic basis of the syndrome. Materials and methods: We included 37 articles that were identified through an electronic search in PubMed and through the reference lists of previously conducted reviews. Studies of 30 or more patients were used to report frequencies of common and less common findings. Genotype–phenotype studies were used to provide additional information when available. Results: Ocular anomalies are present in most patients with CdLS. Common findings include long eyelashes, synophrys, hirsutism of the eyebrows, peripapillary pigment ring, and myopia. Less common findings include hyperopia, ptosis, blepharitis, short palpebral fissure length, down-slanting palpebral fissures, mild microcornea, strabismus, nystagmus, and optic nerve abnormalities. Conclusions: This review provides a comprehensive summary of the ophthalmologic findings in CdLS. Mutations in certain genes may be associated with specific ocular abnormalities, although future genotype studies are needed to further characterize these relationships.     

Coats' Disease,Megalopapilla and Cornelia De Lange Syndrome

Cornelia de Lange syndrome (CdLS), a congenital disorder characterized by growth and mental retardation, hirsutism, and skeletal and cardiac anomalies, has been associated with a number of ophthalmic abnormalities including synophrys, long eyelashes, myopia, nasolacrimal duct obstruction, and ptosis. Only one case of Coats' disease has been described in the setting of this syndrome.¹ We describe a second case of Coats' disease in a five-year-old boy with this condition.     

Intermittent horizontal saccade failure ('ocular motor apraxia') in children.

BACKGROUND: Ocular motor apraxia (OMA) in childhood is a poorly understood condition involving a failure of horizontal saccades. OMA is thought to be rare but the literature indicates wide clinical associations. OMA is often identified by abnormal head movements, but failure of reflexive quick phases has been reported in all but a few patients. The extent of this oculomotor disorder was examined in a large group of children with diverse clinical backgrounds. METHODS: The degree of quick phase failure during horizontal vestibular and optokinetic nystagmus was measured using DC electro-oculography and video in 74 affected children, aged 17 days to 14 years. RESULTS: All children showed an intermittent failure of nystagmic quick phases, except for total failure in one case. Other visuomotor abnormalities were common including saccadic hypometria (85%), low gain smooth pursuit (70%), neurological nystagmus (28%), strabismus (22%), and vertical abnormalities (11%). Non-ocular abnormalities were common including infantile hypotonia (61%), motor delay (77%), and speech delay (87%). There was a wide range of clinical associations including agenesis of the corpus callosum, Joubert syndrome, Dandy-Walker malformation, microcephaly, hydrocephalus, vermis hypoplasia, porencephalic cyst, megalocephaly, Krabbe leucodystrophy, Pelizaeus Merzbacher disease, infantile Gaucher disease, GM1 gangliosidosis, infantile Refsum's disease, propionic acidaemia, ataxia telangiectasia, Bardet-Biedl syndrome, vermis astrocytoma, vermis cyst, carotid fibromuscular hypoplasia, Cornelia de Lange syndrome, and microphthalmos. Perinatal and postnatal problems were found in 15% including perinatal hypoxia, meningitis, periventricular leucomalacia, athetoid cerebral palsy, perinatal septicaemia and anaemia, herpes encephalitis, and epilepsy. Only 27% were idiopathic. CONCLUSION: Quick phase failure is a constant feature of OMA, whereas abnormal head movements were detected in only about half, depending on the underlying diagnosis. This oculomotor sign is better described as an intermittent saccade failure rather than as a true apraxia. It indicates central nervous system involvement, has wide clinical associations, but it is not a diagnosis.     

A novel nonsense B3GALTL mutation confirms Peters plus syndrome in a patient with multiple malformations and Peters anomaly

Peters plus syndrome is an autosomal recessive rare congenital disorder defined by corneal Peters anomaly with short disproportionate stature, development delay and dysmorphic facial features. In addition, cardiac, genito-urinary and/or central nervous system malformations can be present. Mutations in the beta-1,3-galactosyltransferase-like glycosyltransferase gene (B3GALTL) have been reported in patients with Peters plus syndrome prompting phenotype-genotype studies because of the variable clinical spectrum related to the syndrome. A 20 month old boy presenting with bilateral Peters anomaly in association with multiple developmental anomalies including cerebral malformations was found to carry a novel homozygous B3GALTL nonsense mutation [p.Tyr366X]. This is the first stop mutation described in association with this gene. The present report confirms the wide clinical spectrum of Peters plus syndrome, underlines the major clinical criteria of the syndrome and the major implication of B3GALTL gene in this condition. Ophthalmologic examination in multiple developmental anomalies remains an important clinical issue that may lead to specific gene screening. In Peters plus syndrome B3GALTL molecular test provides diagnosis confirmation and improves dramatically genetic counselling for the families.     

A novel nonsense B3GALTL mutation confirms Peters plus syndrome in a patient with multiple malformations and Peters anomaly

Peters plus syndrome is an autosomal recessive rare congenital disorder defined by corneal Peters anomaly with short disproportionate stature, development delay and dysmorphic facial features. In addition, cardiac, genito-urinary and/or central nervous system malformations can be present. Mutations in the beta-1,3-galactosyltransferase-like glycosyltransferase gene (B3GALTL) have been reported in patients with Peters plus syndrome prompting phenotype-genotype studies because of the variable clinical spectrum related to the syndrome. A 20 month old boy presenting with bilateral Peters anomaly in association with multiple developmental anomalies including cerebral malformations was found to carry a novel homozygous B3GALTL nonsense mutation [p.Tyr366X]. This is the first stop mutation described in association with this gene. The present report confirms the wide clinical spectrum of Peters plus syndrome, underlines the major clinical criteria of the syndrome and the major implication of B3GALTL gene in this condition. Ophthalmologic examination in multiple developmental anomalies remains an important clinical issue that may lead to specific gene screening. In Peters plus syndrome B3GALTL molecular test provides diagnosis confirmation and improves dramatically genetic counselling for the families.     

Clinical and ocular findings in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is a congenital abnormality of unknown etiology and variable expressivity, presenting with a characteristic facial appearance, external abnormalities, and clinical features. We report on the external and ocular findings in three cases of BDLS. We note ocular findings not previously seen in the disorder. A large hyperopic ametropia was found in two cases, and lenticular cataracts were noted in one case. Further case studies are necessary to determine if these conditions are consistent in the BDLS.     

Goldenhar and cri-du-chat syndromes: a contiguous gene deletion syndrome?

We report a full-term male infant born to nonconsanguinous parents who had clinical features of Goldenhar syndrome and cri du chat syndrome. At birth, the infant was noted to have dysmorphic features with bilateral preauricular tags, rotated ears, bilateral epicanthic folds, a left epibulbar lipodermoid, and an accessory left nipple. After he was assessed for feeding difficulty and tachypnea, he was found to have esophageal atresia with tracheoesophageal fistula. In addition, he had a high-pitched, cat-like cry, characteristic of cri-du-chat syndrome. He also failed a hearing test. Chromosomal analysis and fluorescence in situ hybridisation studies showed an unbalanced karyotype with a terminal deletion of the segment p14 on the short arm of chromosome 5, which is consistent with the cri-du-chat locus. The association of Goldenhar syndrome and cri-du-chat syndrome in this patient suggests that the chromosome 5p14 locus may harbor a gene implicated with Goldenhar syndrome.     

Ocular defects associated with a duplication of the distal part of the long arm of chromosome 1: a case report

The authors report a case of de novo duplication 1q32-qter present in a patient with dysmorphic syndrome and developmental delay. This article describes the eighth case of partial trisomy 1q32-qter "pure", without chromosomal abnormalities. In the literature, a dysmorphic "syndrome" is described for trisomy 1q32-qter: hypertelorism, low set and malformed ears, prominent forehead, long philtrum, antimongoloid slanting, foot and digital malformations, cardiovascular abnormalities, urogenital abnormalities, and mental retardation. The ocular defects described in previously reported cases include: cataract, strabismus, hypoplasia of the optic disk, microphthalmia, epicanthal folds, ptosis, persistent tunica vasculosa lentis, and hyaloid vessels, but this seems to be nonspecific of this chromosomal abnormality.     

Posterior embryotoxon may not be a forme fruste of Axenfeld-Rieger's Syndrome.

Axenfeld-Rieger Syndrome is a disorder of morphogenesis which is autosomal dominantly inherited. One of the main ocular features associated with Axenfeld-Rieger is posterior embryotoxon, which is a prominent anteriorly displaced Schwalbe's line. This can be found in up to 15% of normal eyes, without any clinical significance or may represent a forme fruste of an anterior segment dysgenesis. Many large case series studies of Axenfeld-Rieger had used the presence of posterior embryotoxon with iris strands extending from the peripheral iris to Schwalbe's line, as inclusion criterion for this condition. We report a case of Axenfeld-Rieger syndrome without posterior embryotoxon and the abnormalities of the angle, but with other features to support the diagnosis of Axenfeld-Rieger Syndrome.     

Mild Optic Nerve Hypoplasia with Retinal Venous Tortuosity in Aarskog (Facial-Digital-Genital) Syndrome

Aarskog syndrome (faciogenital dysplasia) is an X-linked recessive genetic growth disorder characterized by short stature, dysmorphic facies, shawl scrotum, and digital anomalies. The condition was first described in 1970 and the gene responsible is FGD1 (MIM#305400). There are several reported ophthalmic findings associated with Aarskog syndrome which are discussed. We describe a case of Aarskog syndrome with venous tortuosity, optic nerve hypoplasia, and a type-2 antithrombin deficiency.     

Mild optic nerve hypoplasia with retinal venous tortuosity in aarskog (facial-digital-genital) syndrome

Aarskog syndrome (faciogenital dysplasia) is an X-linked recessive genetic growth disorder characterized by short stature, dysmorphic facies, shawl scrotum, and digital anomalies. The condition was first described in 1970 and the gene responsible is FGD1 (MIM#305400). There are several reported ophthalmic findings associated with Aarskog syndrome which are discussed. We describe a case of Aarskog syndrome with venous tortuosity, optic nerve hypoplasia, and a type-2 antithrombin deficiency.     

Rieger syndrome is associated with PAX6 deletion

PURPOSE: Rieger syndrome is an autosomal dominant condition defined by anterior segment dysgenesis in combination with facial, dental, skeletal and umbilical abnormalities. To date Rieger syndrome has been associated with mutations in the PITX2 gene at chromosome 4q25 and a second locus has been found at chromosome 13q14. METHODS: We describe a Rieger syndrome case with all the typical dysmorphic features and the molecular genetic finding by use of FISH analysis of the PAX6 gene. RESULTS: An eight-year-old girl had iris stroma hypoplasia, corectopia and iridogoniodysgenesis. She had an underdeveloped premaxilla and a congenital absence of nine teeth in the maxilla. The front teeth in the mandible were peg-shaped and all teeth were small. There was failure of involution of the periumbilical skin. FISH analysis using probes for the PAX6 gene showed a small deletion for the PAX6 gene on one homologue of chromosome 11. CONCLUSION: Rieger syndrome can -- in addition to PITX2 gene mutations and abnormalities at chromosome 13q14 -- be associated with PAX6 gene abnormalities.     

Congenital corneal opacification in De Barsy syndrome

A newborn male was noted to have bilateral congenital corneal opacification. Findings from examination disclosed a variety of dysmorphic features, including cutis laxa, progeroid aspect, short stature, multiple hyperextensible subluxated joints, muscular hypotonia, and hyperreflexia. Bilateral penetrating keratoplasties were performed; histopathologic examination revealed diffuse epithelial thickening, loss of the Bowman layer, and stromal attenuation with anterior stromal scarring. Special stains showed no deposition of abnormal material in the corneas. Electron microscopy demonstrated absence of Bowman layer differentiation with a paucity of collagen fibers, as well as extensive small elastic fibers in the anterior stroma. The diagnosis of De Barsy syndrome was made, a rare progeroid syndrome associated with characteristic ocular, facial, skeletal, dermatologic, and neurologic abnormalities. De Barsy syndrome should be included in the differential diagnosis of congenital corneal opacification; its distinctive clinical features enable the clinician to easily differentiate it from other causes of congenitally cloudy corneas.     

Lenz microphthalmia: a malformation syndrome with variable expression of multiple congenital anomalies

Lenz microphthalmia is a syndrome of microphthalmia accompanied by multiple congenital anomalies, none of which is unique to the syndrome. The patient described in this paper had, in addition to the microphthalmia, dysmorphic facies and dental anomalies, several features not previously described in this syndrome: synophrys, an isolated cleft of the soft palate, a webbed neck and sacral pits. Other congenital syndromes associated with microphthalmia (oculodentodigital dysplasia, cryptophthalmos and the 10q+ syndrome) were excluded. The frequency of the anomalies described in 22 case reports is presented as a guide to diagnosis in isolated cases.     

Complete Vogt-Koyanagi-Harada Disease and Holmes-Adie Syndrome: Case Report

Abstract

We report a 37-year-old woman with uveitic phase of Vogt Koyanagi Harada disease and tonic pupil, the tonic pupil persisted after other clinical features of this syndrome had disappeared; neurological evaluation shows absent knee and arm tendon reflexes and positive cholinergic supersensitivity test with Pilocarpine 0.125% confirming the diagnosis of Holmes Adie Syndrome.     

痛性眼肌麻痹综合征5例临床分析

目的 :探讨痛性眼肌麻痹综合征 (TolosaHuntSyn drome)的临床特点。方法 :对 5例痛性眼肌麻痹综合征患者的临床资料进行分析。结果 :5例痛性眼肌麻痹综合征患者均符合诊断标准 ,对激素治疗效果佳 ,4例痊愈 ,1例并发化脓性脑膜炎。结论 :痛性眼肌麻痹病因多样 ,临床表现复杂 ,诊断时应慎重。头颅CT、MRI及动脉造影对其诊断有一定的价值。大部分患者对激素疗效好 ,但需警惕炎症播散     

眼面心牙综合征的研究进展

眼面心牙综合征（oculo-facio-cardio-dental syndrome，OFCD 综合征）是一种罕见的 X 染色体显性遗传综合征，特征性表现为眼部、面部、心血管以及牙齿发育异常。眼部主要表现为先天性白内障，且发生率较高。近年来文献对 OFCD 综合征的报道逐渐增多。为提高对 OFCD 综合征的认识，本文对 OFCD 的临床表现、基因研究及综合治疗进展做一综述。（国际眼科纵览，2016，40：213-216）