Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Cilia, ciliopathies and hedgehog-related forebrain developmental disorders.

Development of the forebrain critically depends on the Sonic Hedgehog (Shh) signaling pathway, as illustrated in humans by the frequent perturbation of this pathway in holoprosencephaly, a condition defined as a defect in the formation of midline structures of the forebrain and face. The Shh pathway requires functional primary cilia, microtubule-based organelles present on virtually every cell and acting as cellular antennae to receive and transduce diverse chemical, mechanical or light signals. The dysfunction of cilia in humans leads to inherited diseases called ciliopathies, which often affect many organs and show diverse manifestations including forebrain malformations for the most severe forms. The purpose of this review is to provide the reader with a framework to understand the developmental origin of the forebrain defects observed in severe ciliopathies with respect to perturbations of the Shh pathway. We propose that many of these defects can be interpreted as an imbalance in the ratio of activator to repressor forms of the Gli transcription factors, which are effectors of the Shh pathway. We also discuss the complexity of ciliopathies and their relationships with forebrain disorders such as holoprosencephaly or malformations of cortical development, and emphasize the need for a closer examination of forebrain defects in ciliopathies, not only through the lens of animal models but also taking advantage of the increasing potential of the research on human tissues and organoids.

Examination of the Annular Tendon (Annulus of Zinn) as a Common Origin of the Extraocular Rectus Muscles: 2. Embryological Basis of Extraocular Muscles Anomalies.

Purpose: Many reports have described anomalous connections of the superior rectus (SR) with other extraocular rectus muscles, in which additional heads of the other three rectus muscles likely provided the connections. We examined how these connections are established during fetal development. Methods: We analyzed paraffin-embedded horizontal sections from 25 late-stage fetuses. Horizontal sections are best suited for understanding the mediolateral relationships of muscle origins. Results: We confirmed a common tendinous origin of the lateral rectus (LR), inferior rectus (IR) and medial rectus (MR) muscles that was separated from the SR origin. Notably, eight fetuses (32%) had tendinous or muscular connections between the SR and other rectus muscles that had one of four morphologies: (a) a thin tendon from the SR to the common tendon of the three rectus muscles (2 fetuses), (b) a thin tendon to the LR (one fetus), (c) a thin tendon to the inferior rectus muscle origin (two fetuses), and (d) SR muscle fibers arising from an additional head of the LR (three fetuses). Conclusions: The SR seemed to issue a thin tendon that passed along the inferior or lateral side of the oculomotor nerve. Conversely, the LR and inferior rectus muscle were likely to carry a supernumerary bundle that reached the SR. The accessory head of the medial rectus muscle showed a stable morphology in that it seemed to also provide an anomalous double head. However, the presence of an accessory head in the LR was rare. In contrast with our previously published diagram of the orbital apex, the accessory head of the medial rectus muscle passed along the lateral side of the superior oblique.

Dual roles of the retinal pigment epithelium and lens in cavefish eye degeneration.

Astyanax mexicanus consists of two forms, a sighted surface dwelling form (surface fish) and a blind cave-dwelling form (cavefish). Embryonic eyes are initially formed in cavefish but they are subsequently arrested in growth and degenerate during larval development. Previous lens transplantation studies have shown that the lens plays a central role in cavefish eye loss. However, several lines of evidence suggest that additional factors, such as the retinal pigment epithelium (RPE), which is morphologically altered in cavefish, could also be involved in the eye regression process. To explore the role of the RPE in cavefish eye degeneration, we generated an albino eyed (AE) strain by artificial selection for hybrid individuals with large eyes and a depigmented RPE. The AE strain exhibited an RPE lacking pigment granules and showed reduced expression of the RPE specific enzyme retinol isomerase, allowing eye development to be studied by lens ablation in an RPE background resembling cavefish. We found that lens ablation in the AE strain had stronger negative effects on eye growth than in surface fish, suggesting that an intact RPE is required for normal eye development. We also found that the AE strain develops a cartilaginous sclera lacking boney ossicles, a trait similar to cavefish. Extrapolation of the results to cavefish suggests that the RPE and lens have dual roles in eye degeneration, and that deficiencies in the RPE may be associated with evolutionary changes in scleral ossification.

Pesticide induced visual abnormalities in Asian honey bees (Apis cerana L.) in intensive agricultural landscapes.

Pesticide stress is one of the important factors for global bee declines. Apart from physiological and developmental anomalies, pesticides also impose cognitive damages on bees. The present study investigates the visual acuity of wild populations of honey bees, in an agricultural intensification landscape, and corroborates the findings with controlled laboratory experiments. Even though overall morphometric examinations revealed no significant differences between the populations, correct color choices by bees in pesticide exposed populations were significantly reduced. The study reports, for the first time, the significant reduction in ommatidia facet diameter in these populations, as viewed under scanning electron microscope, along with the molecular underpinnings to these findings. Western blot studies revealed a significant reduction in expression of two visual proteins - blue-sensitive opsin and rhodopsin - in the pesticide exposed populations in both field and laboratory conditions. The novel findings from this study form the basis for further investigations into the effects of field realistic doses of multiple pesticide exposures on wild populations of honey bees.

[Glaucoma Surgery in Anterior Segment Dysgeneses]. / Glaukomchirurgie bei Vorderabschnittsdysgenesien.

Anterior segment dysgeneses are rare conditions, and mostly occur sporadically. The severity of dysgenesis and the number of structures affected are highly variable. Glaucoma occurs in approximately 50% of all patients, either as part of primary chamber angle dysgenesis or secondary to surgery, mostly for removal of congenital cataracts. This review provides a brief overview of the embryological background and the spectrum of phenotypes, such as primary congenital glaucoma, Axenfeld Rieger and Peters Anomaly. Current surgical approaches to lower intraocular pressure are discussed. Special attention is paid to the increasingly used microcatheter-assisted 360° trabeculotomy and glaucoma drainage devices in paediatric glaucoma surgery.

Loss of the neurodevelopmental Joubert syndrome causing protein, Ahi1, causes motor and muscle development delays independent of central nervous system involvement.

Joubert syndrome (JBTS) is a predominantly autosomal recessive neurodevelopmental disorder that presents with characteristic malformations of the cerebellar vermis, superior cerebellar peduncles and midbrain in humans. Accompanying these malformations are a heterogeneous set of clinical symptoms, which frequently include deficits in motor and muscle function, such as hypotonia (low muscle tone) and ataxia (clumsiness). These symptoms are attributed to improper development of the hindbrain, but no direct evidence has been reported linking these in JBTS. Here, we describe muscle developmental defects in a mouse with a targeted deletion of the Abelson helper integration site 1 gene, Ahi1, one of the genes known to cause JBTS in humans. While FVB/NJ Ahi1-/- mice display no gross malformations of the cerebellum, deficits are observed in several measures of motor function, strength, and body development. Specifically, Ahi1-/- mice show delayed physical development, delays in surface reflex righting as neonates, and reductions in grip strength and spontaneous locomotor activity as adults. Additionally, Ahi1-/- mice showed evidence of muscle-specific contributions to this phenotype, such as reductions in 1) myoblast differentiation potential in vitro, 2) muscle desmin expression, and 3) overall muscle mass, myonuclear domain, and muscle fiber cross-sectional area. Together, these data suggest that loss of Ahi1 may cause abnormalities in the differentiation of myoblasts to mature muscle cells. Moreover, Ahi1 loss impacts muscle development directly, outside of any indirect impact of cerebellar malformations, revealing a novel myogenic cause for hypotonia in JBTS.

Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway.

Ocular anterior segment dysgenesis (ASD) is a failure of normal development of anterior structures of the eye, leading to lens opacification. The underlying mechanisms relating to ASD are still unclear. Previous studies have implicated transcriptional factor muscle segment homeobox 2 (Msx2) in ASD. In this study, we used Msx2 conditional knockout (CKO) mice as a model and found that Msx2 deficiency in surface ectoderm induced ASD. Loss of Msx2 function specifically affected lens development, while other eye structures were not significantly affected. Multiple lines of evidence show that calcium signaling pathways are involved in this pathogenesis. Our study demonstrates that Msx2 plays an essential role in lens development by activating a yet undetermined calcium signaling pathway.

Biometric Alterations of Mouse Embryonic Eye Structures Due to Short-Term Folic Acid Deficiency.

PURPOSE: Folic acid (FA) is an essential nutrient for normal embryonic development. FA deficiency (FAD) in maternal diet increases the risk of several defects among the progeny, especially, neural tube defects. The eye begins its development from the neural tube; however, the relationship between FAD and ocular development in the offspring has been little explored and it isn't known how the FAD affects the formation of the eye. Our objective was to analyze the effect of maternal FAD on mouse embryos ocular biometry. METHODS: Female mice C57/BL/6J were distributed into three different groups, according to the assigned diet: control group fed a standard FA diet (2 mg FA/kg), FAD group for short term fed (0 mg FA/kg + 1% succinylsulfathiazole) from the day after mating until day 14.5 of gestation, and FAD group for long term fed the same FA-deficient diet for 6 weeks prior mating and continued with this diet during gestation. A total of 57 embryos (19 embryos of each dietary group) at 14.5 gestational days were evaluated. As indicators of changes in ocular biometry, we analyze two parameters: area and circularity of the lens and whole eye, and the area of the retina. The program used in the treatment and selection of the areas of interest was ImageJ. The statistical analysis was performed by IBM SPSS Statistics 19. RESULTS: Regarding the measures of the area, FA-deficient lenses and eyes were smaller than that of controls. We have also observed increase in the size of the neural retina, spatially, in embryos from females fed FAD diet during long term. On the other hand, as regard to circularity measures, we have seen that eyes and lenses were more circular than control. CONCLUSION: Maternal FAD diet for a very short term generates morphological changes in ocular structures to the offspring.

Cellular rearrangement of the prechordal plate contributes to eye degeneration in the cavefish.

Astyanax mexicanus consists of two different populations: a sighted surface-dwelling form (surface fish) and a blind cave-dwelling form (cavefish). In the cavefish, embryonic expression of sonic hedgehog a (shha) in the prechordal plate is expanded towards the anterior midline, which has been shown to contribute to cavefish specific traits such as eye degeneration, enhanced feeding apparatus, and specialized brain anatomy. However, it is not clear how this expanded expression is achieved and which signaling pathways are involved. Nodal signaling has a crucial role for expression of shh and formation of the prechordal plate. In this study, we report increased expression of prechordal plate marker genes, nodal-related 2 (ndr2) and goosecoid (gsc) in cavefish embryos at the tailbud stage. To investigate whether Nodal signaling is responsible for the anterior expansion of the prechordal plate, we used an inhibitor of Nodal signaling and showed a decreased anterior expansion of the prechordal plate and increased pax6 expression in the anterior midline in treated cavefish embryos. Later in development, the lens and optic cup of treated embryos were significantly larger than untreated embryos. Conversely, increasing Nodal signaling in the surface fish embryo resulted in the expansion of anterior prechordal plate and reduction of pax6 expression in the anterior neural plate together with the formation of small lenses and optic cups later in development. These results confirmed that Nodal signaling has a crucial role for the anterior expansion of the prechordal plate and plays a significant role in cavefish eye development. We showed that the anterior expansion of the prechordal plate was not due to increased total cell number, suggesting the expansion is achieved by changes in cellular distribution in the prechordal plate. In addition, the distribution of presumptive prechordal plate cells in Spemann's organiser was also altered in the cavefish. These results suggested that changes in the cellular arrangement of Spemann's organiser in early gastrulae could have an essential role in the anterior expansion of the prechordal plate contributing to eye degeneration in the cavefish.

Genetic linkage between altered tooth and eye development in lens-ablated Astyanax mexicanus.

The phenotype of lens-ablated Mexican tetra (Astyanax mexicanus) compared to wild-type surface fish has been described and includes, among other effects, eye degeneration, changes in tooth number and cranial bone changes. Here, we investigate the spatiotemporal expression patterns of several key genes involved in the development of these structures. Specifically, we show that the expression of pitx2, bmp4 and shh is altered in the eye, oral jaw, nasal pit and forebrain in these lens-ablated fish. Furthermore, for the first time, we show altered pitx2 expression in the cavefish, which also has altered eye and tooth phenotypes. We thus provide evidence for a genetic linkage between the eye and tooth modules in this fish species. Furthermore, the altered pitx2 expression pattern, together with the described morphological features of the lens-ablated fish suggests that Astyanax mexicanus could be considered as an alternative teleost model organism in which to study Axenfeld-Rieger syndrome (ARS), a rare autosomal dominant developmental disorder that is associated with PITX2 and which has both ocular and non-ocular abnormalities.

RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion.

The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor known to recruit DAB1 - causes rod bipolar cell misposition. Moreover, whereas SOCS7 also controls Muller glia cell lamination, it is not responsible for cone photoreceptor positioning, suggesting that RBX2, most likely through CRL5 activity, controls other signaling pathways required for proper cone localization. Furthermore, RBX2 depletion reduces the number of ribbon synapses and disrupts cone photoreceptor function. Together, these results uncover RBX2 as a crucial molecular regulator of retina morphogenesis and cone photoreceptor function.

Ameliorative impact of Morus alba leaves' aqueous extract against embryonic ophthalmic tissue malformation in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is becoming a serious threat to human health. Morus alba var. multicaulis (Perr.) Loudon (Moraceae) showed a bright future in DM therapy. OBJECTIVE: The study evaluates the antioxidant activity of Morus alba leaves aqueous extract (MLAE) and antidiabetic properties of MLAE in streptozotocin-induced diabetic rats focusing on the ameliorative effects against embryogenesis defects. MATERIALS AND METHODS: MLAE was assayed for bioactive compounds, and antiradical potential. MLAE (100mg/kg body weight) was orally administered to albino rats. DM was induced by intraperitoneal injection of STZ (60mg/kg). The pregnant rats were arranged into 4 groups including control pregnant (C), MLAE-treated group (M), experimental diabetic group (D), and combined diabetic with MLAE-treated group (D-MLAE). The experiment performed in about six months. RESULTS: TPC in MLAE accounted for 11mg GAE/g dry weight (dw) while vitamin C and ß-carotene amounts were 144 and 0.1mg/100g, respectively. MLAE exhibited DPPH, NO and O-2 radical scavenging activities. Treatment of diseased-rats with MLAE resoluted serum glucose levels (378mg/dL), wherein glucose recorded the highest level (830mg/dL) in DM mothers. DM rats recorded the highest level of TC, TG, HDLc, LDLc, and CK, while MLAE treatment reduced those levels. DM rats recorded the highest level of MDA, H2O2, SOD, CAT, GST, GSPase, GSH, GOT, GPT, albumin, bilirubin, arginase, and α-l-fucosidase, while MLAE reduced those levels. Histological photomicrographs of maternal retina showed degenerated ganglionic cells, and neovascularization of nerve fiber layer with edematous inner plexiform layer, and partial loss outer plexiform layer in DM rats. CONCLUSION: MLAE could be used to ameliorate DM. Thus, it might be considered as useful dietary supplements in diabetic patients.

Congenital glaucoma detected by unilateral megalophthalmos on prenatal sonography.

A 36-week male fetus was noted to have isolated right megalophthalmos on prenatal ultrasound and was found to have buphthalmos and congenital glaucoma at birth. Detection of congenital glaucoma at birth may be occasionally possible if abnormal orbit dimensions are noted on late prenatal sonographic examination. Early neonatal intervention may improve the chances to retain vision. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:499-501, 2017.

Fraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases.

OBJECTIVE: Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported. METHOD: We analyzed the prenatal and postnatal fetal phenotype in 38 cases of FS, including 25 pregnancy termination cases, 8 intra-uterine death cases and 4 cases that died after birth. RESULTS: Including both prenatal and postnatal fetal phenotypic evaluation, all cases presented dysmorphic features with nose and ear dysplasia. Renal anomalies and syndactyly were present in 37/38 cases, cryptophtalmos in 36/38, airways anomalies in 30/37 and genital anomalies in 30/35 cases. Anomalies of the abdominal wall such as low set umbilicus and omphalocele were found in 31 cases. Among the 26 cases for which ultrasound data were available, detectable anomalies included oligohydramnios (22), ascites/hydrops (9), renal anomalies (20), evidence for high airways obstruction (11), ophthalmologic anomalies (4), ear dysplasia (2) and syndactyly (2). CONCLUSION: This study shows that the postnatal phenotype of FS is very specific, whereas oligohydramnios hampers the prenatal recognition of the cardinal FS diagnosis criteria. Association of oligohydramnios, kidney agenesis and CHAOS should lead to consider this diagnosis. © 2016 John Wiley & Sons, Ltd.

Six3 regulates optic nerve development via multiple mechanisms.

Malformations of the optic nerve lead to reduced vision or even blindness. During optic nerve development, retinal ganglion cell (RGC) axons navigate across the retina, exit the eye to the optic stalk (OS), and cross the diencephalon midline at the optic chiasm en route to their brain targets. Many signalling molecules have been implicated in guiding various steps of optic nerve pathfinding, however much less is known about transcription factors regulating this process. Here we show that in zebrafish, reduced function of transcription factor Six3 results in optic nerve hypoplasia and a wide repertoire of RGC axon pathfinding errors. These abnormalities are caused by multiple mechanisms, including abnormal eye and OS patterning and morphogenesis, abnormal expression of signalling molecules both in RGCs and in their environment and anatomical deficiency in the diencephalic preoptic area, where the optic chiasm normally forms. Our findings reveal new roles for Six3 in eye development and are consistent with known phenotypes of reduced SIX3 function in humans. Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations.

PHACE syndrome--clinical features, aetiology and management.

UNLABELLED: PHACE syndrome comprises a spectrum of anomalies including posterior fossa malformations, haemangioma, arterial anomalies, cardiac defects and eye anomalies. PHACE should be considered in any patient with a large facial segmental infantile haemangioma (IH), and multidisciplinary management is crucial. Low-dose propranolol is effectively for the treatment of IH associated with PHACE syndrome. Recent evidence suggests IH is comprised of mesoderm-derived haemogenic endothelium. CONCLUSION: The embryonic developmental anomaly nature of IH provides an insight into the origin of PHACE syndrome.

Congenital basis of posterior fossa anomalies.

The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies.

The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye.

Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1(gt/gt) and Daam1(gt/+) embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1(gt/+) mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.

Anterior segment developmental anomalies in a 33-week-old fetus with MIDAS syndrome.

We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.