Genetic carrier screening is a useful tool for couples looking to understand the genetic risk profile of their offspring. However, this method is limited in identifying rare genetic variants. A couple undergoing single euploid embryo transfer (SEET) following planned embryo banking was followed in this study. The patient was a 39-year-old nulliparous female with negative expanded carrier screening (ECS) which included 400 autosomal recessive and X-linked conditions. Her partner was a 39-year-old male with no pertinent past medical history. Clinical pregnancy was achieved following SEET. Unfortunately, the fetus demonstrated a constellation of neurologic malformations at 28 weeks gestation and the couple opted for termination. Amniocentesis was conducted at the time of labor induction revealing unremarkable chromosome analysis and microarray testing. Whole genome sequencing (WGS) noted paternal and maternal variants of the fetal leukemia virus subgroup C cellular receptor family, member 2 protein (FLVCR2). The paternal variant was classified as pathogenic, and the maternal variant was classified as a variant of uncertain significance by the lab. The presence of balletic FLVCR2 variants in the setting of neurologic anomalies was consistent with Fowler syndrome, a rare autosomal recessive condition. This case highlights the inherent limitations of carrier screening in detecting rare genetic disease and marks the first documented case of Fowler syndrome following single euploid embryo transfer.

Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including PDHA1. Typical neonatal brain imaging findings have been described, with a focus on malformative and encephaloclastic features. Fetal brain MRI in PDCD has not been comprehensively described. The aims of this study were (1) to further characterize the fetal brain MRI findings in PDCD using comprehensive fetal imaging and genetic testing and (2) to determine whether markers of diagnosis of PDCD could be identified on prenatal imaging. Fetuses with a diagnosis of PDCD related to a genetic etiology that had undergone fetal MRI were included. Fetuses were identified retrospectively from local databases of 4 fetal diagnostic clinics within tertiary pediatric health care centers. Electronic medical records were reviewed retrospectively: demographics, maternal and pregnancy history, fetal outcomes, and neonatal outcomes (if available) were reviewed and recorded. Fetal and neonatal imaging reports were reviewed; source fetal and neonatal brain MRI scans were reviewed by a single pediatric neuroradiologist (J.W.S.) for consistency. Genetic testing strategies and results including variant type, zygosity, inheritance pattern, and pathogenicity were recorded. Deidentified data were combined and reported descriptively. A total of 10 fetuses with a diagnosis of PDCD were included. 8 fetuses had corpus callosum dysgenesis, 6 had an abnormal gyration pattern, 10 had reduced brain volumes, and 9 had cystic lesions. 1 fetus had intraventricular hemorrhages. 1 fetus had a midbrain malformation with aqueductal stenosis and severe hydrocephalus. 6 fetuses imaged in the second trimester had cystic lesions involving the ganglionic eminences (GEs) while GE cysts were not present in the 4 fetuses imaged in the third trimester. Fetuses with PDCD have similar brain MRI findings to neonates described in the literature, although some of these findings are subtle early in pregnancy. Additional features, such as cystic lesions of the GEs, are noted in the second trimester in fetuses with PDCD. These may represent an early diagnostic marker of PDCD, although more data are needed to validate this association. Early diagnosis of PDCD using fetal MRI may inform genetic counseling, pregnancy decision making, and neonatal care planning.

Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including PDHA1. Typical neonatal brain imaging findings in PDCD have been described, with a focus on malformative features and chronic encephaloclastic changes. However, fetal brain MRI imaging in confirmed PDCD has not been comprehensively described. We sought to demonstrate the prenatal neurological and systemic manifestations of PDCD determined by comprehensive fetal imaging and genomic sequencing. All fetuses with a diagnosis of genetic PDCD who had undergone fetal MRI were included in the study. Medical records, imaging data, and genetic testing results were reviewed and reported descriptively. Ten patients with diagnosis of PDCD were included. Most patients had corpus callosum dysgenesis, abnormal gyration pattern, reduced brain volumes, and periventricular cystic lesions. One patient had associated intraventricular hemorrhages. One patient had a midbrain malformation with aqueductal stenosis and severe hydrocephalus. Fetuses imaged in the second trimester were found to have enlargement of the ganglionic eminences with cystic cavitations, while those imaged in the third trimester had germinolytic cysts. Fetuses with PDCD have similar brain MRI findings to neonates described in the literature, although some of these findings may be subtle early in pregnancy. Additional features, such as cystic cavitations of the ganglionic eminences, are noted in the second trimester in fetuses with PDCD, and these may represent a novel early diagnostic marker for PDCD. Using fetal MRI to identify these radiological hallmarks to inform prenatal diagnosis of PDCD may guide genetic counseling, pregnancy decision-making, and neonatal care planning.

Porencephaly is an uncommon neurological condition characterized by cystic cavities or holes in the cerebral hemispheres of the brain filled with cerebrospinal fluid. There are two types of porencephaly: acquired porencephaly, also known as pseudo-porencephaly, and congenital porencephaly, also known as true porencephaly. Acquired porencephaly, also known as encephaloclastic porencephaly, typically results from late prenatal or perinatal vascular lesions caused by arterial ischemic stroke or venous thrombosis. Congenital porencephaly, or genetic porencephaly, arises from maldevelopment during early neuronal migration. Brain lesions associated with congenital porencephaly are thought to result from irregularities in cell migration during development and are often linked to additional brain deformities. Lesions resulting from degenerative disorders caused by vascular, viral, or traumatic events are classified under acquired porencephaly. Familial cases of porencephaly are believed to be caused by mutations in the COL4A1 gene, which lead to brain small-vessel disease with haemorrhage. Due to the variability in lesion size and location, porencephaly presents with a wide range of clinical symptoms. We report a case of a 41-year-old male who is diagnosed as a case of porencephaly with complaints of withdrawn behaviour, decreased interaction, suspiciousness, delusion of persecution and delusion of reference. These symptoms have started in the past two months. This case report contributes to the growing body of research suggesting a potential link between porencephaly and psychosis, despite the limited available data. Further investigation is required to validate this connection and explore the underlying mechanisms. Continued research into this potential association may help guide future psychosis diagnosis and treatment plans.

Porencephaly is defined as a fluid-filled cavity of variable size in the brain cortex. It is regarded as a congenital condition and is typically considered a developmental or an encephaloclastic defect. Our hypothesis is that postnatal traumatic events in the first few months of life may represent a cause of canine and feline porencephaly that is more common than generally suspected. The aims of this study were to retrospectively investigate porencephaly in a large population of dogs and cats, detect MRI features that might be useful to differentiate postnatal acquired traumatic forms from congenital/perinatal porencephaly, and define the prevalence of seizure activity in porencephalic patients. This is a double-center, descriptive, retrospective case series. Databases were searched for cases within a 17-year time span that involve dogs and cats with an MRI-based diagnosis of cerebral cavitary lesions. Animals were included if a complete signalment and an exhaustive MRI of the brain were available. Besides the porencephalic lesions, MRIs of the head were reviewed to detect concomitant musculoskeletal abnormalities. Thirty-two cases involving nine cats and twenty-three dogs were selected. Of all the cases, 21.9% were aged six years or older at the time of diagnosis. All patients in which the neuroanatomical localization was available showed clinical signs of a prosencephalic disorder. Epileptic seizures were observed in 71.8% of cases. A single porencephalic cavity was found in 78.1% of cases. The most affected cerebral lobe was the parietal lobe (n = 20). The defects involved both the grey and white matter in 78.1% of cases. Twenty cases showed concomitant musculoskeletal abnormalities overlying the porencephalic cavities. Fourteen of twenty cases showed evidence of fractures, of which thirteen showed depression of the calvarium and twelve masticatory muscle abnormalities. Of these, seven of fourteen had a history consistent with a head trauma in the first period of life. The recognition of skull fractures and muscular abnormalities closely associated with the porencephalic cavity may support a diagnosis of a postnatal traumatic origin of porencephaly. Therefore, this study highlights the importance of evaluating musculoskeletal structures in the MRIs of the heads of porencephalic cases.