Retinoblastoma is a pediatric ocular malignancy caused by biallelic inactivation of the RB1 gene, with genetic testing crucial for determining heritability. This retrospective observational study analyzed the genotypic and phenotypic profiles of 200 RB patients from North India who underwent genetic testing at a tertiary eye hospital between January 2022 and April 2024. Targeted RB1 gene analysis was performed using next-generation sequencing on blood samples, with methylation specific-multiplex ligation-dependent probe amplification detecting large deletions or duplications. Phenotypic features, including age of onset, laterality, disease severity, metastasis, and recurrence, were assessed. Among 200 patients, 113 had unilateral RB, 85 bilateral, and two trilateral, with mean onset ages of 33 months for unilateral and 14 months for bilateral cases. Intraocular tumors were present in 84%, extraocular extension in 16%, and metastasis in 16% of cases. Pathogenic RB1 variations were identified in 48% of patients, predominantly in bilateral cases (77.08%). A trend toward mutation clustering in exons 14-21 was observed in 57% of patients. While bilateral disease showed a statistically significant correlation with genotype for non-sense variations (p = 0.05); no other clinical features were linked to specific mutations. This study highlights unique regional genotypic patterns and emphasizes the potential for cost-effective testing strategies in resource-limited settings. Cat eye syndrome (CES), also known as Schmid-Fraccaro syndrome, is a rare genetic disorder named for the vertical iris coloboma observed in some affected individuals. The condition is classically characterized by a triad of features—iris coloboma, anal atresia, and preauricular pits or tags. However, CES can also involve a range of abnormalities affecting the neurodevelopmental, ocular, auricular, nasal, cardiovascular, gastrointestinal, and urogenital systems (see Image. Schematic Diagram Showing Iris Coloboma in Cat Eye Syndrome).  The clinical presentation of CES is variable, with differences in affected organ systems, prognosis, genetics, and heritability among individuals. CES is a rare chromosomal disorder first described in the early 1960s by Schmid and Fraccaro. This condition is characterized by a partial tetrasomy or trisomy of chromosome 22q11.1-q11.2. The name "cat eye" originates from ocular colobomas—iris defects—present in about half of affected individuals, which give the pupil a distinctive keyhole or cat-eye appearance. Although ocular coloboma is the eponymous hallmark, CES is fundamentally a multisystem genomic disorder with highly variable expressivity, spanning a spectrum from nearly asymptomatic to severe anomalies across ocular, cardiac, renal, gastrointestinal, skeletal, and neurodevelopmental domains. The association between ocular coloboma and anal atresia was first described by Haab in 1878. The genetic alteration is due to a small supernumerary marker chromosome (sSMC), which was first described in 1965. Schachenmann et al reported 3 pediatric patients and 1 patient’s mother who carried an additional, abnormally small chromosome featuring a submedian centromere, while the rest of the karyotype appeared normal. This sSMC contains the CES critical region (CESCR), located within the proximal portion of chromosome 22q11.2, between the centromere and the LCR22-A region. Additional genetic conditions related to chromosome 22 include the oculo-auriculo-vertebral spectrum (OAVS), DiGeorge syndrome, and mosaic trisomy 22.  At the genetic level, CES arises from a supernumerary marker chromosome, often dicentric, composed of material from chromosome 22. In approximately 90% of cases, this marker contains 2 extra copies of the proximal 22q11 region (tetrasomy), while a smaller proportion exhibits an additional copy (trisomy). The critical region encompasses approximately 1.5 to 2 Mb and includes multiple dosage-sensitive genes whose overexpression is believed to contribute to the diverse phenotypic features of CES. Molecular cytogenetic techniques, such as fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH), and, more recently, genome-wide single-nucleotide polymorphism (SNP) microarrays, have replaced traditional karyotyping for precise delineation of the supernumerary chromosome and identification of the breakpoints. This high-resolution genomic mapping is crucial for definitive diagnosis, genotype-phenotype correlations, and recurrence-risk counseling. Clinically, CES is remarkably heterogeneous. The classic triad comprises iris coloboma, preauricular skin tags or pits, and anal atresia or other anorectal malformations. However, no single feature is universally present. Iris coloboma appears in 40% to 60% of cases, preauricular anomalies in up to 70%, and anorectal malformations in about 30% to 50%. Cardiac defects, most commonly total or partial atrioventricular septal defects and tetralogy of Fallot, occur in approximately half of patients and are a major contributor to early morbidity and mortality. Renal anomalies, reported in 20% to 40% of cases, may include unilateral renal agenesis, duplex collecting systems, hydronephrosis, and vesicoureteral reflux. Skeletal abnormalities range from vertebral segmentation defects to limb anomalies. Otolaryngological manifestations may include hearing loss from middle-ear dysplasia. Less commonly, gastrointestinal anomalies beyond anorectal malformations—such as duodenal atresia or Hirschsprung disease—have also been documented. Neurodevelopmental outcomes in CES vary widely. Although some children achieve developmental milestones within normal limits, others present with global developmental delay, intellectual disability, or features consistent with autism spectrum disorder. Hypotonia during infancy and feeding difficulties—often related to underlying gastrointestinal anomalies—may further compromise early growth. Growth parameters can be affected, with some patients exhibiting short stature or failure to thrive; however, many ultimately achieve normal height and weight. Behavioral phenotypes—such as attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders—have also been reported, emphasizing the importance of comprehensive developmental and psychological assessment. Ophthalmic manifestations in CES extend beyond the iris coloboma. Additional anomalies such as chorioretinal colobomas, microphthalmia, cataracts, microcornea, and strabismus can contribute to visual impairment. A comprehensive ophthalmologic evaluation includes slit-lamp biomicroscopy to assess anterior segment abnormalities, indirect ophthalmoscopy for posterior segment examination, and optical coherence tomography (OCT), when available, to delineate the extent of colobomatous defects. Early detection and management of refractive errors, amblyopia, and strabismus are essential to support optimal visual development. Surgical intervention for coloboma is rarely indicated and is typically reserved for cases involving severe aniridia-like photophobia or significant cosmetic concerns (see Image. Schematic Diagram Showing Chorioretinal Coloboma in Cat Eye Syndrome). The management of CES depends on the organ systems involved and the severity of associated malformations. Given the significant clinical heterogeneity, an individualized, interprofessional approach is essential. This activity outlines the genetic and phenotypic spectrum of CES and outlines strategies for tailoring medical care to each patient’s needs. Cardiac evaluation at diagnosis is mandatory. Echocardiography within the first weeks of life is essential for detecting structural heart disease; in moderate-to-severe cases, surgical repair during infancy may be lifesaving. Long-term cardiology follow-up is critical to monitor for residual defects, arrhythmias, and pulmonary hypertension. Similarly, early renal ultrasonography is recommended to identify anatomical anomalies, guide urologic management, and prevent complications such as hypertension or renal insufficiency. Gastroenterological and colorectal management primarily focuses on anorectal malformations. Posterior sagittal anorectoplasty (PSARP) is the standard repair for imperforate anus, with timing and technical details tailored to the patient’s specific anatomy and overall health. Nutritional support—ranging from gavage or gastrostomy feeding in neonates to dietary modifications in older children—is essential, especially when gastrointestinal motility disorders or malabsorption are present. Audiologic and otologic care begins with newborn hearing screening. Conductive hearing loss due to middle ear anomalies may require interventions such as tympanostomy tubes or myringotomy. Speech therapy and educational support, tailored to the child’s developmental needs, are essential for optimizing communication outcomes. Genetic counseling for families includes discussion of recurrence risk, which is generally low (<1%) in de novo cases but higher in familial instances when a parent carries the small supernumerary marker chromosome in a balanced form. Secondary complications may include endocrine disorders, particularly growth hormone deficiency and thyroid dysfunction, necessitating regular endocrinologic screening. Orthopedic evaluations focus on detecting scoliosis and limb-length discrepancies. Dental and orthodontic assessments help identify malocclusion and enamel hypoplasia. Psychosocial support for families—including referrals to patient advocacy groups and peer support networks—promotes coping strategies and shared experiences. From a research perspective, CES provides valuable insights into gene dosage effects in contiguous-gene syndromes. The 22q11 region implicated in CES overlaps with that of DiGeorge syndrome (22q11.2 deletion), yet their phenotypes differ, reflecting divergent consequences of haploinsufficiency versus gene overexpression. Current studies focus on elucidating the roles of candidate genes such as CECR1 (which encodes adenosine deaminase 2) and CECR2 (involved in chromatin remodeling) in contributing to CES manifestations. Animal models with targeted duplications of the 22q11 region are under development to investigate relevant developmental pathways. Additionally, next-generation sequencing techniques show promise in detecting cryptic rearrangements and refining genotype–phenotype correlations, ultimately improving prognostic accuracy and identifying potential therapeutic targets. In summary, CES is a complex, multisystem chromosomal disorder. While its hallmark features include ocular coloboma, ear anomalies, and anorectal malformations, the condition also encompasses a wider phenotypic spectrum affecting the cardiac, renal, skeletal, neurodevelopmental, and endocrine systems. Accurate diagnosis relies on high-resolution cytogenetic and molecular techniques. Effective management requires coordinated multidisciplinary care, involving specialties from neonatology and cardiology to ophthalmology, urology, and developmental pediatrics. As advances in molecular genetics continue, they will enhance personalized prognostic counseling and enable the development of targeted therapies, ultimately improving outcomes for individuals and families affected by this rare but informative genomic syndrome.

Objectives  The abducens nerve has a long, serpentine subarachnoid course with complex topographical relationships, rendering abducens nerve palsy the most common ocular motor cranial nerve palsy in adults and second most common in pediatric patients, with anatomical variants reported in the literature. Preoperative awareness of abducens nerve variant anatomy may help prevent inadvertent intraoperative injury. Design  This study is a case report with a review of the abducens nerve anatomy and variants. Setting  The study setting included outpatient, inpatient, and operating room in the neurosurgery department of a quaternary referral center. Participants  The study included a woman in her early 30s with a diagnosis of petrous meningioma. Main Outcome Measures  In vivo documentation of a type 3 abducens nerve duplication was carried out. Results  A left extended retrosigmoid craniotomy was recommended for the petroclival meningioma resection. Intraoperatively, a complete duplication of the left abducens cisternal segment was encountered and photographed. The left unilateral abducens nerve duplication was confirmed with postoperative volumetric magnetic resonance imaging using the FIESTA (fast imaging employing steady-state acquisition) sequence, revealing the union of the duplicated cisternal abducens nerves into a single trunk from Dorello's canal distally. Conclusion  Abducens nerve variants are uncommon, and although reported in the setting of cadaveric dissection, in vivo documentation of them is limited. This case report of an in vivo type 3 abducens nerve duplication with intraoperative photographic and radiographic images highlights the need for clinical awareness to avoid inadvertent intraoperative injury.

MYCN-amplified RB1 wild-type (MYCNampRB1+/+) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCNampRB1+/+ from the most prevalent RB1-/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN. The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCNampRB1+/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCNampRB1+/+ and RB1-/- retinoblastoma subtypes.

A 33-5/7, 1570 g dichorionic diamniotic twin presented with cryptorchidism, failed hearing examination (both ears), poor feeding, profound hypoglycemia, coagulopathy, conjugated hyper-bilirubinemia, hydronephrosis, and hypotension. Microarray sent with results of whole genome SNP microgray analysis detected an interstitial duplication of the chromosomal segment 4q35 1q35.2. On this basis, telemedicine screening was performed to evaluate for ocular abnormalities in association with abnormal gene testing. Unilateral advanced retinopathy was noted affecting the right eye, with mature vascularization in the left eye. This infant was managed in concordance with retinopathy of prematurity guidelines, despite not making screening criteria. Off-label intravitreal bevacizumab injection (0.625 mg in 0.025 mL) resulted in full vascular maturation assessed by fluorescein angiography 6 months later. This represents the first description and management of retinopathy in 4q duplication syndrome. [Ophthalmic Surg Lasers Imaging Retina 2024;55:228-230.].

Pituitary stalk abnormalities are one of the causes of hypopituitarism. Isolated pituitary stalk duplication with a single pituitary gland is extremely rare with only a few cases reported to date. The present case has a different clinical picture as compared to the cases that were previously reported in the literature. A 2 years 6-month-old male child, a product of nonconsanguineous marriage, presented with short stature, micropenis with unilateral undescended testis, and delayed motor milestones. His bone age was delayed by 6 months. On further evaluation, he was found to be euthyroid, with stimulated growth hormone (GH) and stimulated gonadotropin levels were suboptimal, whereas the cortisol and the prolactin were normal. Magnetic resonance imaging of the pituitary revealed pituitary stalk duplication with a single pituitary gland of normal dimensions and fused tuber cinereum and mammillary body. To our knowledge, only 7 cases with isolated pituitary stalk duplication were reported. The presenting complaint could be primarily of hypopituitarism like short stature or a neurologic complaint or ocular abnormality. The pituitary hormone deficiencies are variable with GH deficiency being the most common as seen in our case. Other associated features could be the morning glory disc anomaly, moyamoya disease, pituitary adenoma or hypoplasia, split hypothalamus, and sellar dermoid. Pituitary stalk duplication is a developmental disorder that is diagnosed only by imaging. Patients should be evaluated for hypopituitarism, particularly the GH and gonadotrophins deficiency, and also screened for associated neurologic and ocular abnormalities.