Congenital Cataracts and Microphakia with Retinal Dysplasia and Optic Nerve Hypoplasia in a Calf

Case Description. A two-month-old, female, Aberdeen-Angus calf was presented for congenital cataracts and blindness in both eyes (OU). The dam had a reported history of visual defects (not specified) and had produced other affected calves (per owner history). Ophthalmic examination revealed mature bilateral cataracts, attenuation of the iridic granules, persistent pupillary membranes, and dyscoric pupils. Additionally, the calf had a poor body condition, prognathism, dome-shaped head, excessive nasal drainage, limb contracture, and fever. Histopathology of both eyes revealed lenticular degeneration (congenital cataracts), retinal dysplasia, and optic nerve hypoplasia. BVDV IHC detected antigen within only the left eye (OS), consisting of intrahistiocytic and endothelial immunoreactivity within the ciliary body, iris, and choroid. No BVDV immunoreactivity could be detected in the right eye (OD). This case highlights the unique ocular changes present in in utero BVDV infection of cattle with a different immunohistochemical staining profile than previously described.

Microphthalmia and Optic Nerve Hypoplasia Induced by Maternal Coronavirus Infection?

Possible mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy is still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Three perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded (two cases confirmed by PCR, the third one based on clinical findings). In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, or drug use during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as strongly support COVID19 vaccination recommendations for pregnant women.Trial registration number: NCT04741412Date of registration: November 18, 2020

ALG3-CDG: a patient with novel variants and review of the genetic and ophthalmic findings

Background ALG3-CDG is a rare autosomal recessive disease. It is characterized by deficiency of alpha-1,3-mannosyltransferase caused by pathogenic variants in the ALG3 gene. Patients manifest with severe neurologic, cardiac, musculoskeletal and ophthalmic phenotype in combination with dysmorphic features, and almost half of them die before or during the neonatal period. Case presentation A 23 months-old girl presented with severe developmental delay, epilepsy, cortical atrophy, cerebellar vermis hypoplasia and ocular impairment. Facial dysmorphism, clubfeet and multiple joint contractures were observed already at birth. Transferrin isoelectric focusing revealed a type 1 pattern. Funduscopy showed hypopigmentation and optic disc pallor. Profound retinal ganglion cell loss and inner retinal layer thinning was documented on spectral-domain optical coherence tomography imaging. The presence of optic nerve hypoplasia was also supported by magnetic resonance imaging. A gene panel based next-generation sequencing and subsequent Sanger sequencing identified compound heterozygosity for two novel variants c.116del p.(Pro39Argfs*40) and c.1060 C > T p.(Arg354Cys) in ALG3. Conclusions Our study expands the spectrum of pathogenic variants identified in ALG3. Thirty-three variants in 43 subjects with ALG3-CDG have been reported. Literature review shows that visual impairment in ALG3-CDG is most commonly linked to optic nerve hypoplasia.

Ophthalmic Manifestation and Pathological Features in a Cohort of Patients With Linear Nevus Sebaceous Syndrome and Encephalocraniocutaneous Lipomatosis

Purpose: This study aimed to figure out the association between ophthalmic and pathological features in patients with Linear Nevus Sebaceous Syndrome (LNSS) and in patients with Oculoectodermal Syndrome—Encephalocraniocutaneous Lipomatosis (OES-ECCL).Methods: It is a retrospective, non-consecutive, observational case series. Twenty-seven patients (12 with LNSS and 15 with OES-ECCL, 41 eyes) referred to the Department of Ophthalmology of the Shanghai Ninth People's Hospital between 2000 and 2020 were included. The mean age of the study population for the first-time consult was 5.7 years, ranging from 3 months to 34 years. Clinical notes, pathological records, and imaging findings were reviewed in all the patients.Results: Fourteen (51.9%) cases showed bilateral ocular involvement. Epibulbar choristomas were seen in all the patients. All the lesions involved the conjunctiva and cornea simultaneously. Multiple lesions were observed in 12 eyes. Of the 14 excised lesions, 11 were found to be complex choristomas. Further, 24 (89%) patients had eyelid coloboma. Also, 13 patients (48%) were diagnosed with strabismus, and 12 patients (44%) had abnormal fundus imaging, including optic nerve hypoplasia.Conclusions: LNSS and OES-ECCL shared common ophthalmic features, including epibulbar choristomas with distinctive characteristics, eyelid coloboma, strabismus, and optic nerve hypoplasia. The complex choristoma was found to be associated with the diseases. These specific patterns can be diagnostic clues to distinguish them from other syndromes, such as craniofacial defects, and to remind ophthalmologists that such patients require additional dermatological and neurological examinations and referral. Moreover, a thorough evaluation of ocular conditions is imperative for early interventions.

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common—and clinically important—endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.