Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service

Purpose: Hereditary causes are an important etiological category of childhood blindness. This study reports the real?world experience of a developing ocular genetic service. Methods: The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North?West India. Children presenting to the genetic clinic with congenital or late?onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel?based sequencing/chromosomal microarray) was outsourced to third?party laboratories with the cost of the test being borne by the patient. Results: Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Conclusion: Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Research progress of Sox2 gene in eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Sox2 gene is a member of sex determination region of Y chromosome(SRY)related gene family, and it is one of the key transcription factors to maintain the pluripotency and self-renewal characteristics of embryonic stem cells. Sox2 participates in a variety of biological processes, such as regulating cell proliferation and apoptosis, and participating in the formation and development of tumors. However, the review literature on the role of Sox2 gene in eye diseases has not been reported. This article reviews the expression level of Sox2 gene, related signal pathways and clinical application potential, so that readers can understand more comprehensive the role of Sox2 gene in eye diseases, and to carry out more in-depth research.

Newborn transient patterned hyperpigmentation and anophthalmia / Patrón de hiperpigmentación transitoria del recién nacido y anoftalmia

Abstract Background: Transient pigmentary lines of the newborn are uncommon cutaneous lesions of unknown etiology. To date, only a few cases have been described. Case report: A patient with a combination of transient pigmentary lines and ocular malformation is described. Molecular analysis of the SRY-box 2 (SOX2) and MIFT genes was conducted to rule out any monogenetic etiology. Conclusions: Worldwide, this is the eighth case of transient pigmentary lines of the newborn reported, and the first associated with anophthalmia. No mutations in the analyzed genes (SOX2 and MIFT) were identified. Therefore, somatic mutations could be responsible for this anomaly.

Resumen Introducción: Las líneas transitorias pigmentarias del recién nacido son lesiones cutáneas poco comunes. A la fecha, pocos casos se han descrito. Caso clínico: Paciente neonato con la combinación de líneas transitorias hiperpigmentadas y una malformación ocular. Se realizó secuenciación molecular de los genes SOX2 y MIFT para descartar una etiología monogénica. Conclusiones: En todo el mundo, este es el octavo caso reportado de líneas transitorias hiperpigmentadas del recién nacido, y el primero asociado con anoftalmia. No se identificaron mutaciones en los genes estudiados (SOX2 y MIFT). Por lo tanto, las mutaciones somáticas pueden ser la causa de la afección.

Bilateral Anophthalmia: Literature, Review and Case Report

Introduction:Anophthalmia which is the congenital absence of the eyes could be bilateral or congenital, it occurs globally although it is rare. It is usually in association with other systemic congenital abnormalities. Case Report:A case of a female baby delivered at a primary health center in Port Harcourt, Nigeria who had bilateral anophthalmia is reported here along with review of literature Magnetic Resonant Imaging (MRI) of brain and orbit was used to confirm the diagnosis which showed absence of both globes, with hypoplasia of the orbits as well as the extraocular muscles, the optic nerves could not be differentiated from the visualized intra-orbital structures. All other systems were essentially normal. This is an exceptional case in Port Harcourt, Nigeria, as literature search shows that no other case has been reported in Port Harcourt. She is currently being followed up at the paediatric, ophthalmology and ENT clinics of the University of Port Harcourt teaching hospital.

Importancia de la neuroimagen en la anoftalmia/microftalmia congénita neonatal: a propósito de un caso / Importance of neuroimaging in neonatal congenital anophthalmia/microphthalmia: a case report

Introducción: La Anoftalmia/Microftalmia es una malformación ocular congénita que se caracteriza por la reducción variable del volumen del globo ocular, la misma requiere de estudios imagenológicos para un diagnóstico más preciso. Objetivo: Demostrar la importancia de la neuroimagen en el diagnóstico y orientación de la microftalmia/anoftalmia neonatal congénita bilateral. Presentación del caso: Se hace referencia a un recién nacido con diagnóstico clínico de anoftalmia/microftalmia de manera inicial que después de realizar estudios de neuroimagen se constataron otras malformaciones del sistema nervioso central que permitieron orientar el diagnóstico hacia un síndrome genético definido. Durante el examen físico inicial se constató hipertelorismo, orejas de implantación baja, fisura palatina, ano anterior y ausencia de los globos oculares en ambos lados. La Resonancia magnética nuclear mostró esbozos de cristalinos rudimentarios, ubicados en zona atípica y esbozo de nervio óptico incompleto del lado derecho. No se observaron globos oculares. Observándose además múltiples imágenes de aspecto quístico bilaterales en las áreas orbitarias que desplazan los cristalinos rudimentarios por conflicto de espacio. Este paciente requirió estudios de neuroimagen para determinar si se trataba de una anoftalmia/microftalmia y para orientar el diagnóstico de displasia septo-óptica que organizó el pensamiento clínico hacia un posible Síndrome de Morsier. En este caso se realizó diagnóstico diferencial con otras causas asociadas a estas malformaciones oculares. Conclusiones: Los estudios imagenológicos del cerebro de los pacientes con anoftalmia / microftalmia en la etapa neonatal permiten orientar un diagnóstico preciso y precoz que favorece una intervención multidisciplinaria temprana(AU)

Introduction: Anophthalmia/microphthalmia is a congenital eye malformation that is characterized by the variable reduction of the volume of the ocular globe, which requires imaging studies for a more precise diagnosis. Objective: To demonstrate the importance of neuroimaging in the diagnosis and management of neonatal congenital bilateral anophthalmia/microphthalmia. Case Presentation: We describe the case of a newborn with an initial clinical diagnosis of anophthalmia/microphthalmia in which, after carrying out neuroimaging studies, other malformations of the central nervous system were confirmed, allowing to guide the diagnosis towards a defined genetic syndrome. During the initial physical exam, hypertelorism, low set ears, palatine fissure, anterior anus, and absence of the ocular globes in both sides were verified. The magnetic resonance imaging showed signals of rudimentary crystalline located in an atypical area, and signals of incomplete optic nerve of the right side. Ocular globes were not observed. Multiple cyst-like bilateral images were also observed in orbital areas, displacing the rudimentary crystalline lens due to space limitations. Discussion: This patient required neuroimaging studies to determine if she had an anophthalmia/microphthalmia and present a guide for the diagnosis of septo-optic dysplasia that organized the clinical thinking towards a possible Morsier Syndrome. In this case, a differential diagnosis with other causes associated to these ocular malformations was made. Conclusions: The imaging studies of the brain of the patients with anophthalmia/microphthalmia in the neonatal period allows to guide a precise and early diagnosis that favors an early multidisciplinary intervention(AU)

Novel compound heterozygous mutations of ALDH1A3 contribute to anophthalmia in a non-consanguineous Chinese family

Abstract Anophthalmia is a rare eye development anomaly resulting in absent ocular globes or tissue in the orbit since birth. Here, we investigated a newborn with bilateral anophthalmia in a Chinese family. Exome sequencing revealed that compound heterozygous mutations c.287G > A (p.(Arg96His)) and c.709G > A (p.(Gly237Arg)) of the ALDH1A3 gene were present in the affected newborn. Both mutations were absent in all of the searched databases, including 10,000 in-house Chinese exome sequences, and these mutations were confirmed as having been transmitted from the parents. Comparative amino acid sequence analysis across distantly related species revealed that the residues at positions 96 and 234 were evolutionarily highly conserved. In silico analysis predicted these changes to be damaging, and in vitro expression analysis revealed that the mutated alleles were associated with decreased protein production and impaired tetrameric protein formation. This study firstly reported that compound heterozygous mutations of the ALDH1A3 gene can result in anophthalmia in humans, thus highlighting those heterozygous mutations in ALDH1A3 should be considered for molecular screening in anophthalmia, particularly in cases from families without consanguineous relationships.

A new method to solve anophthalmic contracted socket in embedding orbital implant in 114 cases / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To perform a new method for orbital implant and contracted socket through one time and its results. ·METHODS:Totally 114 patients 114 eyes, from January 2008 to June 2014, with contracted socket participated in this study. We incised the bulbar conjunctiva horizontally and excised scar tissue, then implanted the hydroxyapatite in the four extraocular muscles and tightly sutured the Tenon ' capsule. After that, we put the superior and inferior conjunctival petals backwards and sutured them to the Tenon ' s capsule. All the patients were divided into four groups according to the vertical diameter length of the conjunctival defect area:GroupⅠ:≤5mm; Group Ⅱ: 6-10mm; Group Ⅲ: 11-15mm; and Group Ⅳ: ≥16mm. These patients were followed up for 6mo to 3y to observe the conjunctival sac shaping and growth of conjunctiva. ·RESULTS:There were 64 cases in GroupⅠ, 31 cases in Group Ⅱ, 16 cases in Group Ⅲ and 3 cases in Group Ⅳ. All patients ' conjunctival defect was covered by new conjunctiva and scar tissue 4 to 6wk after surgeries. Ten cases had contracted socket; 2 cases had orbital implant exposure, requiring reoperation. Of the 114 cases, 8 had contracted socket and could use a smaller conformer, 106 could use a normal size conformer. ·CONCLUSION: When the conjunctival defect was ≤15mm, this new method can address the orbital implant and contracted socket at the same time. While it was ≥16mm, flap transplantation is necessary.

Manejo clinicoquirúrgico de la anoftalmia y de la microftalmia congénitas / Clinical and surgical management of congenital anophthalmia and microphthalmia

La anoftalmia y la microftalmia congénitas son defectos oculares poco frecuentes, generalmente identificados en el momento del nacimiento, como resultado de alteraciones en la organogénesis del ojo a consecuencia de la acción de factores genéticos y ambientales durante el desarrollo embrionario. Estas anomalías provocan grave discapacidad visual a las personas que la padecen, por lo que generan gran repercusión en el ámbito psicosocial. El diagnóstico y el tratamiento precoz permitirán la estimulación visual a edad temprana, la corrección parcial o total de la anomalía y una mejor calidad de vida de estos pacientes, aun cuando no sea posible evitar la ceguera. La conducta ante estas afecciones es compleja y controversial; constituyen un reto para el cirujano oculoplástico y para el protesista. Por esta razón se decide realizar una revisión bibliográfica para profundizar en el adecuado manejo clinicoquirúrgico de estas anomalías(AU)

Congenital anophthalmia and microphthalmia are infrequent ocular defects at the time of birth as a result of alterations in the organ genesis of the eye caused by the action of genetic and/or environmental factors during the embryonic development. These anomalies bring about serious visual impairment to people who suffer it and have great impact on the psychosocial context. Early diagnosis and treatment allows visual stimulation at younger ages, partial or total correction of the anomaly and a better quality of life for these patients, even when it is not possible to avoid blindness. The behavior before these affections is complex and controversial; it represents a challenge for the oculoplasty surgeon and the prosthesis specialist. The objective of this literature review was to delve into the adequate clinical and surgical management of these anomalies(AU)

Síndrome cerebro-óculo-nasal con diagnóstico prenatal / Cerebro-óculo-nasal syndrome with prenatal diagnosis

El síndrome cerebro-óculo-nasal se caracteriza por anomalías del sistema nervioso central, oculares y nasales. La prevalencia de este síndrome es muy baja, y aún no se ha identificado la etiología de esta condición. Se presenta el caso de un paciente con sospecha cínica de este síndrome con diagnóstico prenatal por ecografía 2D y 3D. Se realiza una revisión de la literatura de los casos previamente reportados.

The cerebro-óculo-nasal syndrome is characterized by central nervous system abnormalities, ocular and nasal. The prevalence of this syndrome is very low, and has not yet identified the etiology of this condition. We report the case of a patient with suspected PJS cynical prenatal diagnosis by 2D and 3D ultrasound. A review of the literature of previously reported cases.

Urinary System anomalies at birth.

Background: Congenital anomalies of urinary system are common and are found in 3-4% of population, and lethal urinary anomalies account for 10% of termination of pregnancy. Methods: A study was done to know the incidence of congenital anomalies at birth for the period of 4 months from May 99 - Sept 99 at Cheluvamba hospital attached to Mysore medical college. Congenital anomalies in the still births, live births and aborted fetuses >20 weeks were studied along with the case history and ultrasound reports. Aborted fetuses and still born babies were collected for autopsy after the consent of parents. These babies were fixed in 10% formalin and autopsy was done after fixing, and anomalies were noted. Results: Total births during study period were 3000. There were 61 babies with congenital anomalies and 6 babies had anomalies of urinary system. Among the urinary system anomalies 1 baby had bilateral renal agenesis, 1 baby had unilateral renal agenesis with anophthalmia (Fraser syndrome), 2 babies had Multicystic dysplastic kidney disease (MCDK) and 1 live baby had hydronephrosis due to obstruction at pelvi ureteric junction, and 1 live female baby had polycystic kidneys. Conclusion: Incidence of urinary system anomalies in the present study was 2 per 1000 births. U/S detection of urinary anomalies varies with period of gestation, amniotic fluid volume and visualisation of urinary bladder. Autopsy helps to detect renal agenesis.

A child with mosaicism for deletion (14)(q11.2q13).

In this case report we describe a child with a de novo deletion in the (q11.2q13) region of chromosome 14. The child presented with dysmorphic features - anophthalmia, microcephaly, and growth retardation. Cytogenetic studies showed mosaicism. The karyotype was 46,XX,del(14)(q11.2;q13) [16] /46,XX [9]. We compared the features observed in this child with that of others with the same deletion reported in scientific literature and found that this is the first report of a child mosaic for this deletion. It is also the first time it has been reported in association with anophthalmia.

Tratamento das cavidades anoftálmicas secas com transplante de glândulas salivares labiais / Treatment of dry anophthalmic cavities with labial salivary glands transplantation

OBJETIVOS: Estudar os efeitos clínicos da secreção das glândulas salivares labiais na lubrificação das cavidades anoftálmicas secas, avaliar a durabilidade dos resultados e apresentar a técnica do transplante. A aplicação desse procedimento em cavidades anoftálmicas secas é inédita na literatura. MÉTODOS: Estudo prospectivo das cirurgias de enxertos glândulo-mucosos, compostos pela mucosa labial e glândulas salivares subjacentes, colocados no fórnice conjuntival de 5 pacientes com cavidades anoftálmicas que apresentavam grave xeroftalmia e retração dos fórnices conjuntivais. As cirurgias foram realizadas durante o período de julho/00 a janeiro/09. Dois pacientes já haviam sido tratados previamente com enxertos de mucosa ou de pele. A técnica do procedimento é descrita em detalhes. Os parâmetros que serviram para a análise comparativa dos resultados foram o quadro clínico, o aspecto do revestimento da cavidade, o ressecamento da superfície da prótese e a frequência do uso de colírios lubrificantes. RESULTADOS: Em todos os casos foi constatada a integração do enxerto e a melhora dos parâmetros avaliados. A evolução mostrou persistência e estabilidade dos resultados. CONCLUSÕES: A lubrificação da superfície da cavidade produzida pela secreção salivar mostrou ser eficiente, bem tolerada e constante, resultando maior conforto do uso da prótese. Infere-se que essa melhor lubrificação obtida ajuda a prevenir a evolução do processo de retração da cavidade. O transplante das glândulas salivares labiais para o fórnice conjuntival demonstrou ser um procedimento de fácil execução, acessível a qualquer cirurgião oftalmologista.

PURPOSE: To study the clinical effects of labial salivary glands' secretion used as ocular lubricant in anophthalmic cavities with severe xerophthalmia; to evaluate the evolution of the results; and to present the surgical technique. This procedure application in dry anophthalmic cavities is new in the literature. METHODS: Prospective study of patients presenting anophthalmic cavities with severe xerophthalmia and conjunctival fornix retraction treated with labial salivary glands transplantation to the conjunctival fornices. The surgeries were performed in five patients during the period of July 2000 to January 2009. In two cases the fornix retraction was previously treated with mucosa or skin graft. The surgical procedure technique is described in details. The postoperative comparative analysis was based on the clinical picture, the cavity surface aspect, the dryness of the cavity and prosthesis and the frequency of lubricant eye drops use. RESULTS: In all cases both graft integration and improvement of the evaluated parameters were observed. The evolution proved the persistence and stability of the results. CONCLUSION: The salivary secretion produced by the transplanted labial glands proved to be efficient as conjunctival lubricant, well tolerated and permanent, making the use of the prosthesis more comfortable. This improvement helps to prevent the progression of the cavity retraction process. Labial salivary glands graft into the anophtalmic cavity is a simple procedure and accessible to any ophthalmic surgeon.

Cavidades anoftálmicas atípicas / Atypical anophthalmic cavities

OBJETIVO: Determinar el comportamiento de las cavidades anoftálmicas atípicas en nuestro centro en cuanto a edad, sexo, causas de pérdida del globo ocular, técnica quirúrgica y sus principales alteraciones. MÉTODOS: Se realizó un estudio descriptivo de tipo prospectivo de 239 pacientes con diagnóstico confirmado de cavidades anoftálmicas atípicas que acudieron a la consulta de prótesis del ICO Ramón Pando Ferrer en el período de junio a diciembre del 2007. RESULTADOS: El 3 por ciento fueron menores de 20 años, el 30 por ciento entre los 21 y los 40 años, el 43 por ciento entre los 41 y 60 años y el 24 por ciento mayores de 60 años. El 74 por ciento fueron del sexo masculino. La pérdida del globo ocular por traumatismo fue en 115 pacientes para un 48,1 por ciento seguido de infecciones y glaucoma. El 69,5 por ciento fueron eviscerados y el 30,5 por ciento enucleados. El 64 por ciento tuvo patología conjuntival de ellos el 28 por ciento por retracción del férnix inferior. La pseudoptosis se presentó en el 49 por ciento. CONCLUSIONES: Las cavidades anoftálmicas atípicas resultaron más frecuentes entre los 41 y 60 años. Predominó el sexo masculino. Las principales causas de pérdida del globo ocular fueron el traumatismo seguido de infecciones. Predominó la evisceración como técnica quirúrgica. La mayoría de las cavidades atípicas resultaron ser por pérdida de fondo de saco inferior y malposiciones palpebrales

OBJECTIVE: To determine the situation of atypical anophthalmic cavities in our center in terms of age, sex, causes of eyeball loss, surgical technique and main alteration of the technique. METHODS: A prospective descriptive study was conducted in 239 patients with confirmed diagnosis in the period of June to December 2007. RESULTS: In this group of patients, 3 percent were under 20 years of age, 30 percent aged 21 to 40 y, 43 percent was in 41-60 y group and 24 percent were over 60 years. Males accounted for 74 percent. The eyeball loss due to trauma affected 115 patients for 48,1 percent followed by infections and glaucoma. In these patients, 69,5 percent were eviscerated and 30,5 percent were enucleated. Conjunctival pathology was present in 64 percent of them whereas lower fornix retraction affected 28 percent. Pseudoptosis was observed in 49 percent. CONCLUSIONS: Atypical anophthalmic cavities were more common in the 41-60y age group. Males prevailed. The main causes of the eyeball loss were trauma and infections. Evisceration was the most used surgical technique. Most of these atypical cavities were due to loss of the lower sac fundus and to palpebral malpositions

Perfil biopsicossocial de portadores de anoftalmia no sul de Minas Gerais - Brasil / Biopsychosocial profile of patients with anophthalmia in the south of Minas Gerais - Brazil

OBJETIVO: Avaliar o perfil biopsicossocial de portadores de anoftalmia, com ênfase no impacto psicológico e funcional da perda ocular e na reintegração social dessa população. MÉTODOS: Realizou-se estudo transversal com 84 pacientes (50 do gênero masculino e 34 do feminino), reabilitados ou em processo de reabilitação com próteses oculares, avaliados por meio de questionário que contemplava dimensões como: etiologia da perda ocular, grau de adaptação à prótese e impacto nas atividades profissionais, sociais e escolares. RESULTADOS: O olho direito foi afetado em 45,2 por cento dos pacientes, o olho esquerdo em 51,2 por cento, e os demais apresentavam anoftalmia bilateral. Relataram dificuldade, atual ou já superada, de adaptação à visão monocular 47,5 por cento dos participantes. No gênero masculino as principais causas da anoftalmia foram os traumatismos oculares por acidentes (54 por cento), e no feminino, as doenças adquiridas (38,2 por cento). Na população estudada, a perda ocular ocorreu, em média, aos 20,5 ± 18,4 anos, e o tempo decorrido até a primeira reabilitação protética foi de 8,6 ± 13,1 anos. A maioria dos pacientes (66,1 por cento) relatou satisfação e boa adaptação à prótese ocular. Sentimentos de tristeza, vergonha e timidez foram freqüentemente relatados. CONCLUSÃO: Pacientes com anoftalmia freqüentemente apresentam transtornos psíquicos e/ou funcionais que dificultam sua readaptação ao meio social, profissional e familiar, o que é agravado por fatores econômicos e pela carência de serviços públicos que ofereçam tratamento reabilitador. A realização de campanhas de esclarecimento à população também pode ser útil para a prevenção das causas que levam à perda ocular.

PURPOSE: To evaluate the biopsychosocial profile of patients with anophthalmia, with emphasis on the psychological and functional impact of eye loss and the social reintegration of this population. METHODS: Prospective analyses of 84 patients (50 males and 34 females), rehabilitated or in the rehabilitation process with ocular prostheses were interviewed by means of a questionnaire with dimensions involving the etiology of the ocular defect, degree of adaptation to the ocular prosthesis, and impact on professional, family and social activities. RESULT: The right eye was affected in 45.2 percent of the patients, the left eye in 51.2 percent, and the rest of the patients had bilateral anophthalmia. Difficulty in adapting to monocular vision was reported by 47.6 percent of the patients. The main causes of anophthalmia in males were eye injuries due to accidents (54 percent), and, in females, acquired diseases (38.2 percent). For the total studied population, the eye loss occurred at a mean of 20.5 ± 18.41 years, and the elapsed time until the first rehabilitation with ocular prosthesis was of 8.6 ± 13.10 years. Most patients (66.1 percent) reported satisfaction and good adaptation to the prosthesis. Feelings of sadness, shame and shyness were frequently reported. CONCLUSION: Anophtalmic patients often exhibit psychic and/or functional disorders which hinder their social, professional and family readaptation, and this is aggravated by both economic factors and lack of public services that provide rehabilitative treatment. Public information campaigns could also be useful to prevent causes that lead to ocular loss.

A Case of XX Male Syndrome with Anophthamia

XX male has a male phenotype with testes or gonads of testicular type and a female chromosomal constitution of 46, XX with no evidence of either ovarian tissue or female genital organs. Generally, they have normal male genitalia and all are infertile. We experienced a neonate with anophthalmia, hypospadia, small penis, and normal testes, whose chromosomal analysis demonstrated 46, XX. Polymerase chain reaction revealed the existence of a sex-determining region of Y (SRY). These findings suggest that the translation of an SRY on the X chromosome led to the development of a male phenotype. We report the case with a review of the related literature.