Axenfeld-Rieger syndrome/anomaly (ARS) is a rare genetic disorder with an autosomal dominant inheritance pattern, characterized by dysgenesis of the anterior segment of the eye. It may present with systemic anomalies (Axenfeld-Rieger syndrome) or without (Axenfeld anomaly) and may sometimes be associated with multiple congenital malformations. The estimated prevalence ranges from 1 in 50,000 to 1 in 200,000 live births, with an approximate rate of 1 in 100,000, but no epidemiological studies have been conducted to date. A clinical diagnosis of Axenfeld-Rieger syndrome requires the presence of both Axenfeld and Rieger ocular anomalies, accompanied by extraocular systemic features. Ocular manifestations include iris abnormalities, posterior embryotoxon, juvenile-onset glaucoma (a common complication), and dysgenesis of the iridocorneal angle with iridocorneal adhesions. The most commonly observed systemic anomalies include: umbilical defects; craniofacial dysmorphism; dentofacial abnormalities, such as Class III malocclusion due to maxillary hypoplasia, oligodontia, dental malformations (taurodontism, root dysplasia), microdontia, hypodontia, and anodontia; hearing impairment (partial or complete sensorineural hearing loss); and cardiac anomalies, including non-congenital heart disease and mitral valve insufficiency. Additional anomalies may include hypospadias in males, anal stenosis, endocrine disorders (notably growth retardation) secondary to pituitary dysfunction, psychomotor delay, and various neurological malformations such as Dandy-Walker malformation, mega cisterna magna, posterior fossa cysts, cerebellar vermis hypoplasia, ventriculomegaly, aprosencephaly, cerebral atrophy, microcephaly, arteriovenous malformations (AVM), and digital anomalies such as camptodactyly. Diagnosis is typically made in infancy, based on iris anomalies such as corectopia (displacement of the pupil), polycoria (multiple pupils), and iris hypoplasia. Posterior embryotoxon is frequently observed upon slit-lamp examination. Given the clinical variability, a comprehensive pediatric assessment is essential to identify systemic anomalies and distinguish Axenfeld-Rieger syndrome from the isolated Axenfeld anomaly.

Anencephaly is a serious developmental defect of the central nervous system in which the brain and cranial vault are grossly malformed. The cerebrum and cerebellum are reduced or absent, but the hindbrain is present. Anencephaly is a part of the neural tube defect spectrum. This defect results when the neural tube fails to close during the third to fourth weeks of development, leading to fetal loss, stillbirth, or neonatal death. To find out probable principal risk factors for the appearance of anencephaly. This study was conducted to compare between pregnancies affected by anencephaly in 2002-2011 with those notified in the period 1991-2001. Statistical analysis was undertaken using chi-squared tests. Results had shown that anencephaly fetuses with a weight less than 1500 g were significantly higher in the period 2002-2011 than in 1991-2001 (P=0.003; OR= 4.32; CI= 1.62-11.53). Anencephaly cases aged more than 20 weeks of gestation (WG) were statistically elevated than cases aged less than 20 WG (P= 0.003). Maternal parity was associated with the appearance of anencephaly, where uni- or multiparous cases mothers were more likely to have an offspring with anencephaly than nulliparous mothers. Consanguinity presented a significant risk factor for the occurrence of anencephaly (P= 0.003). A logistic regression was run to examine the impact of several variables, only the maternal age was statistically significant. This study clarified fields where efforts should be intensified, and surveillance data developed to prevent this malformation. Introduction: Anencephaly is a serious developmental defect of the central nervous system in which the brain and cranial vault are grossly malformed. The cerebrum and cerebellum are reduced or absent, but the hindbrain is present. Anencephaly is a part of the neural tube defect spectrum. This defect results when the neural tube fails to close during the third to fourth weeks of development, leading to fetal loss, stillbirth, or neonatal death. Aim: To find out probable principal risk factors for the appearance of anencephaly. Methods: This study was conducted to compare between pregnancies affected by anencephaly in 2002-2011 with those notified in the period 1991–2001. Statistical analysis was undertaken using chi-squared tests. Results: Results had shown that anencephaly fetuses with a weight less than 1500 g were significantly higher in the period 2002-2011 than in 1991-2001 (P=0.003; OR= 4.32; CI= 1.62-11.53). Anencephaly cases aged more than 20 weeks of gestation (WG) were statistically elevated than cases aged less than 20 WG (P= 0.003). Maternal parity was associated with the appearance of anencephaly, where uni- or multiparous cases mothers were more likely to have an offspring with anencephaly than nulliparous mothers. Consanguinity presented a significant risk factor for the occurrence of anencephaly (P= 0.003). A logistic regression was run to examine the impact of several variables, only the maternal age was statistically significant. Conclusion: This study clarified fields where efforts should be intensified, and surveillance data developed to prevent this malformation.

In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that first strike the eye, the almost obligate presence of cerebral malformations suggests a disruptive event in the cephalic pole of the forming embryo. No major monogenic contribution has been recognized today for this type of malformation.

Anticoagulation of pregnant woman with mechanical prosthetic heart valves is associated with significant maternal and fetal risks. We describe a case of dorsal midline dysplasia in a fetus at 11 weeks' gestation. The mother was receiving warfarin therapy at a dose of 7.5 mg daily following a mechanical mitral valve replacement for rheumatic heart disease. Histological assessment revealed a meningocele with hemorrhage. No cerebellar or cerebral tissue was present in the skull confirming anencephaly. A multidisciplinary approach in pregnant women with mechanical prosthetic heart valves is essential in order to improve fetal outcomes.

Bovine frontonasal dysplasias like arhinencephaly, synophthalmia, cyclopia and anophthalmia are sporadic congenital facial malformations. In this study, computed tomography, necropsy, histopathological examinations and whole genome sequencing on an Illumina NextSeq500 were performed to characterize a stillborn Limousin calf with frontonasal dysplasia. In order to identify private genetic and structural variants, we screened whole genome sequencing data of the affected calf and unaffected relatives including parents, a maternal and paternal halfsibling. The stillborn calf exhibited severe craniofacial malformations. Nose and maxilla were absent, mandibles were upwardly curved and a median cleft palate was evident. Eyes, optic nerve and orbital cavities were not developed and the rudimentary orbita showed hypotelorism. A defect centrally in the front skull covered with a membrane extended into the intracranial cavity. Aprosencephaly affected telencephalic and diencephalic structures and cerebellum. In addition, a shortened tail was seen. Filtering whole genome sequencing data revealed a private frameshift variant within the candidate gene ZIC2 in the affected calf. This variant was heterozygous mutant in this case and homozygous wild type in parents, half-siblings and controls. We found a novel ZIC2 frameshift mutation in an aprosencephalic Limousin calf. The origin of this variant is most likely due to a de novo mutation in the germline of one parent or during very early embryonic development. To the authors' best knowledge, this is the first identified mutation in cattle associated with bovine frontonasal dysplasia.