Neural tube defects (NTDs) are severe congenital anomalies resulting from improper neural tube closure. Craniorachischisis totalis, the most extreme form, involves failure of neural tube formation along the entire cranio-spinal axis. This rare condition is fatal, with limited reported cases globally. We report a case of a 35-year-old G3P1L1A1 woman admitted at 20 weeks and 4 days gestation for medical termination of pregnancy following second-trimester ultrasound findings of anencephaly and spinal dysraphism. The patient began folic acid supplementation only after pregnancy confirmation. The fetus exhibited acrania, bifid vertebrae, exposed neural tissue, frog-eye deformity, and limb contractures. Butterfly vertebrae was observed in infantogram. Retrospective ultrasound review revealed an absent cranial vault, disorganized brain matter, and a large open spinal defect extending to the upper lumbar region. Genetic and infectious panels were largely unremarkable, except for reactive rubella IgG. Craniorachischisis totalis arises from failure of neural tube closure, potentially linked to genetic mutations, folate deficiency, and multiple maternal risk factors. Here, we also revisit the various theories of neural tube closure. Early prenatal diagnosis and counseling are critical for managing craniorachischisis. Periconceptional folic acid supplementation remains the most effective preventive measure.

We present a rare case of trisomy 18 of maternal origin in a pregnancy with omphalocele, craniorachischisis, and ectopia cordis. A 38-year-old woman, G3P1A1, was diagnosed with fetal anencephaly, an extrathoracic heart (ectopic cordis), deformity of spine and a stomach-and-intestine-containing omphalocele by prenatal ultrasound at 12 weeks of gestation. The patient's husband was 39 years old and healthy. The patient had no significant past medical history. She was a nonsmoker, with a pre-pregnancy BMI of 23.7 and was not diabetic. There was no family history of malformations, diseases, or teratogenic medication. The patient had not received assisted reproductive technology during this pregnancy. The pregnancy was terminated in the 13th gestational week. Additional anomalies detected after termination of the pregnancy included small and triangular face, abnormal posturing of hands, clubfoot and craniorachischisis. Crown-heel length was 5.5 cm consistent with a 12-13-week gestational age. Postnatal cytogenetic analysis of chorionic villi obtained by placental sampling revealed a karyotype of 47, XX + 18. Polymorphic DNA marker analysis by quantitative fluorescent polymerase chain reaction (QF-PCR) assays showed a maternal origin of the extra chromosome 18. The concomitant omphalocele, ectopia cordis and craniorachischisis may be related to trisomy 18. Genetic analysis of the postmortem tissue and the analysis of the parental origin of the extra chromosome 18 using QF-PCR, provide valuable information for genetic counseling.

SLMAP3 is a tail-anchored membrane protein that targets subcellular organelles and is believed to regulate Hippo signaling. The global loss of SLMAP3 causes late embryonic lethality in mice, with some embryos exhibiting neural tube defects such as craniorachischisis. We show here that SLMAP3 -/- embryos display reduced length and increased width of neural plates, signifying arrested convergent extension. The expression of planar cell polarity (PCP) components Dvl2/3 and the activity of the downstream targets ROCK2, cofilin, and JNK1/2 were dysregulated in SLMAP3 -/- E12.5 brains. Furthermore, the cytoskeletal proteins (γ-tubulin, actin, and nestin) and apical components (PKCζ and ZO-1) were mislocalized in neural tubes of SLMAP3 -/- embryos, with a subsequent decrease in colocalization of PCP proteins (Fzd6 and pDvl2). However, no changes in PCP or cytoskeleton proteins were found in cultured neuroepithelial cells depleted of SLMAP3, suggesting an essential requirement for SLMAP3 for these processes in vivo for neurulation. The loss of SLMAP3 had no impact on Hippo signaling in SLMAP3 -/- embryos, brains, and neural tubes. Proteomic analysis revealed SLMAP3 in an interactome with cytoskeletal components, including nestin, tropomyosin 4, intermediate filaments, plectin, the PCP protein SCRIB, and STRIPAK members in embryonic brains. These results reveal a crucial role of SLMAP3 in neural tube development by regulating the cytoskeleton organization and PCP pathway.

We report the case of a 33-week-old female fetus born with craniorachischisis to a gravida 5, para 4 (3104) mother with no previous history of conceiving a child with a neural tube defect. Craniorachischisis is characterized by anencephaly and an open defect extending from the brain to the spine and is the most severe and fatal type of neural tube defect. Although the cause of neural tube defects is hypothesized to be multifactorial and is usually sporadic, the risk is increased in neonates born to mothers with a family history or a previous pregnancy with neural tube defect, both of which are not present in the index case. This case is unique in that only during the fifth pregnancy did the couple conceive a child with a neural tube defect, emphasizing that folic acid supplementation, the sole preventive measure proven to decrease the risk of neural tube defects, remains to be important in the periconceptual period for all women of childbearing age.