Fetal Brain Injury in Rhesus Isoimmunization Fetus.

This report presents a rare fetal and neonatal complication brain injury (encephalomalacia and ventriculomegaly) as a consequence of severe fetal anemia resulting from Rhesus (Rh) isoimmunization. A 28-year-old gravida 4 para 3 woman was referred at 21+4 weeks of gestation to the fetal medicine clinic as a case of Rh isoimmunization. Fetal ultrasound showed a normal anatomy scan with normal brain structure, but with severe fetal anemia. The patient was treated with multiple intrauterine transfusions, but still developed complications post-transfusions. This case shows that severe cerebral developmental anomalies can occur because of severe fetal anemia secondary to Rh isoimmunization, such as in this case - ventriculomegaly and encephalomalacia. It has been concluded that proper antenatal counseling and early intervention for severe fetal anemia are beneficial to prevent such complications from occurring. It is crucial to consider appropriate antenatal and postnatal radiological imaging for such cases.

Fetal Diaphragmatic Eventration: A Case Report.

BACKGROUND: Congenital diaphragmatic eventration (CDE) is a rare congenital malformation that is well described in the pediatric literature. In contrast to congenital diaphragmatic hernia (CDH), there is no physical defect in the diaphragm with CDE. Prenatal differentiation of the two pathologies represents a diagnostic and prognostic challenge. CASE: A 26-year-old nulliparous woman was evaluated for a fetal thoracic mass. At 22 weeks, detailed morphology ultrasound revealed a multi-cystic structure in the left side of the thorax. Differential diagnosis included cystic congenital adenomatoid pulmonary malformation and CDH. Left diaphragmatic eventration was added to the differential diagnosis when serial ultrasound at 36 weeks showed the left hemidiaphragm as a thin membrane bulging into the fetal chest with the left kidney in a higher position underneath. The male infant was delivered vaginally at 373 weeks. CT imaging at 2 days of life showed findings consistent with left diaphragmatic eventration with protrusion of small bowel loops and the left kidney underneath. The infant was successfully extubated 3 days later and remained on nasal cannula until discharge on day 17 of life. At 6 months, the infant required operative repair owing to increasing shortness of breath. CONCLUSION: CDE is a rare and difficult diagnosis to consider prenatally. Probable associated features may aid diagnosis. Additional, larger case series are needed to improve prenatal differentiation of this condition.

Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH.

Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by severe fetal growth restriction, microcephaly, a distinct facial appearance, ichthyosis, skeletal anomalies, and perinatal lethality. The pathogenesis of NLS remains unclear despite extensive clinical and pathological phenotyping of the >70 affected individuals reported to date, emphasizing the need to identify the underlying genetic etiology, which remains unknown. In order to identify the cause of NLS, we conducted a positional-mapping study combining autozygosity mapping and whole-exome sequencing in three consanguineous families affected by NLS. Surprisingly, the NLS-associated locus identified in this study was solved at the gene level to reveal mutations in PHGDH, which is known to be mutated in individuals with microcephaly and developmental delay. PHGDH encodes the first enzyme in the phosphorylated pathway of de novo serine synthesis, and complete deficiency of its mouse ortholog recapitulates many of the key features of NLS. This study shows that NLS represents the extreme end of a known inborn error of serine metabolism and highlights the power of genomic sequencing in revealing the unsuspected allelic nature of apparently distinct clinical entities.