Novel variants in the PAX6 gene related to isolated aniridia.

Aniridia, which is a rare congenital defect of the eye, consists of iris hypoplasia or aplasia, and additional ocular abnormalities. It is most commonly caused by autosomal dominant PAX6 gene mutations. However, in about 30% of cases, it is associated with chromosomal rearrangements in the 11p13 region. The aim of this study was to identify the potential PAX6 gene variants, which could cause the isolated aniridia. Eight patients with isolated aniridia were included in this study. MLPA analysis allowed in the past to exclude large structural rearrangements of the PAX6 and adjacent genes like WT1. Blood samples were collected from the patients (and their families in familial cases) and genomic DNA was extracted from peripheral blood leukocytes and buccal cells. The amplification of the 11 exons of the PAX6 gene was performed. Bidirectional Sanger Sequencing was conducted for the identification of the potentially pathogenic variants, and for the segregation analysis of the identified variant in the family. The results were analyzed with the use of CodonCode Aligner software. In three patients, aniridia was sporadic, whereas in another five cases, the eye defect was familial. The potentially pathogenic variants in the PAX6 gene were found in 6 out of 8 patients with aniridia. We identified four known (c.781C > T, c.607C > T, and c.949C > T twice), and two novel variants (c.258_265del and c.495_496insG). Point mutations in the PAX6 gene are the most frequent cause of aniridia. The investigation of the genetic background of the disease is essential for patients to evaluate recurrence risk in the offspring.

Ophthalmologic Manifestations of Neuroblastoma: A Systemic Review.

Neuroblastoma (NBL) is the most common extracranial solid tumor found in pediatric patients. It develops from the sympathetic tract tissue. Although the symptoms are associated with tumor localization, sometimes NBL is manifested as ophthalmologic disorders. In this paper, we describe their incidence and the correlation with the prognosis. We searched 2 databases (PubMed and Web of Science) for papers published before April 2022, and concerned pediatric patients with NBL, which caused ophthalmologic changes. We collected 7 papers assessing the occurrence of ophthalmologic findings in the NBL patients, as well as 68 case reports presenting children with orbital changes and NBL, or with other tumors stemming from the sympathetic ganglia. The statistical analysis was performed to synthetize the data. The ophthalmologic signs occurred in 17.89% of the NBL cases; however, they were observed on presentation in 10.68%. The isolated ocular presentation was found in 2.56% of patients, whereas Horner syndrome was most frequent. The ophthalmologic symptoms correlated with patients' age, primary tumor site, and survival rate. NBL may be challenging to diagnose in cases with isolated ophthalmologic manifestations. Numerous possible ocular signs can be observed, which emphasize the need for multidisciplinary care with regard to the NBL patients.

Incidence of Horner syndrome associated with neuroblastic disease.

PURPOSE: Horner syndrome (HS) manifests in unilateral ptosis, miosis, enophthalmos, and anhedonia. It is most commonly caused by trauma or surgical procedures, but can also occur in pediatric patients as a result of tumors, especially neuroblastoma (NBL). The objective of this study was to analyze the incidence of HS in patients diagnosed with NBL. METHODS: A retrospective analysis of data collected at the Department of Pediatric Oncology, Hematology, and Transplantology from 2004 to 2019 was performed. The study group included 119 patients younger than 18 years old, with 62 girls and 57 boys. All of them were diagnosed with a neuroblastic tumor. RESULTS: Among the 119 patients, eight children (6.72%) were diagnosed with HS associated with NBL. Three of these patients presented to the clinic with HS, whereas HS developed after the surgical procedure to remove the tumor in four patients. The adrenal gland was the most frequent localization of the tumor. However, HS occurred more frequently in patients with mediastinum tumors. As a presenting symptom, HS occurred in 2 of 11 cases (18.18%) with mediastinum localization. All of the patients with HS were younger than 2 years old. CONCLUSION: Investigation of the cause of isolated HS is crucial because it can be the first symptom of NBL. However, the surgical procedure itself increases the risk of HS as a complication of NBL treatment.