中隔視神経形成異常症／ドモルシア症候群

Congenital pituitary hormone deficiency (CH) is a rare disorder that usually involves deficient production of growth hormone (GH) and other pituitary hormones. Many cases are syndromic, affecting other aspects of craniofacial development and sometimes other organs. There are many genes implicated in congenital pituitary hormone deficiency, and some of them also cause more severe disorders like septo-optic dysplasia (SOD) and holoprosencephaly (HPE). It is not clear why mutations in the same gene can cause such variable clinical features. In addition, the molecular etiology of many cases is not identified with current genetic testing approaches. To realize the promise of the human genome project, more genetic causes need to be identified, and the basis for variable clinical presentations needs to be better understood. In this review we provide information about the overlapping genetic causes of this spectrum of disorders in humans, discuss the influence of genetic background and environment on presentations, and highlight animal models that expand our understanding of how genetic and environmental factors can synergize to generate diverse phenotypes. Evidence for genetic and environmental contributions to this spectrum of disorders is strong.

Background/Objectives: Absent septum pellucidum (ASP) is a rare fetal midline brain finding that may occur in isolation or alongside broader central nervous system (CNS) malformations, genetic disorders, or septo-optic dysplasia (SOD). Accurate prenatal diagnosis and counseling remain challenging because apparently isolated ASP may be reclassified following fetal magnetic resonance imaging (MRI), postnatal neuroimaging, or specialist assessment. This structured narrative review aimed to synthesize current evidence on prenatal imaging findings, associated anomalies, genetic evaluation, and postnatal outcomes in fetuses with ASP. Methods: This structured narrative review used PRISMA-informed reporting. PubMed and Google Scholar were searched for full-text English-language studies published from 2014 through the updated search date (8 June 2026). Data on gestational age at diagnosis, imaging classification, associated anomalies, genetic testing, postnatal assessment, and neurodevelopmental, ophthalmological, and endocrine outcomes were extracted. Study methodological quality was appraised using Joanna Briggs Institute tools. Results: Seven studies comprising 342 fetal ASP cases were included. Of these, 94 cases (27.5%) were classified as isolated ASP prenatally, but only 57 remained isolated postnatally when follow-up data were available. SOD was confirmed after birth in 11 of 94 (11.7%) fetuses with prenatally isolated ASP. As definitions, imaging protocols, genetic testing strategies, and follow-up duration differed substantially across studies, these pooled values are descriptive observations rather than formal quantitative estimates. Conclusions: ASP is a heterogeneous prenatal finding. The prognosis is most favorable when ASP remains isolated following a detailed prenatal and postnatal evaluation. Multidisciplinary follow-up involving fetal medicine, neuroradiology, genetics, ophthalmology, endocrinology, and neurology is essential for risk stratification and counseling.

OBJECTIVES: To establish gestational age-specific reference ranges for two new indices, the forehead-anterior cerebral artery angle (FACAA) and forehead-anterior cerebral artery distance (FACAD), and to objectively evaluate their diagnostic effectiveness, measured using Doppler technology with microvascular flow imaging, for identifying holoprosencephaly, even the semilobar and lobar types, in early pregnancy. METHODS: We evaluated FACAA and FACAD in 462 normal fetuses between 12 and 34 gestational weeks (GW) to generate normative reference ranges. Additionally, we evaluated these two indices in 41 fetuses with holoprosencephaly and 34 fetuses with similar two-dimensional ultrasound features (the study group), including 20 fetuses with agenesis of the corpus callosum and 14 with isolated absent septum pellucidum/septo-optic dysplasia. RESULTS: In the normal group, FACAA was almost stable throughout pregnancy, whereas FACAD increased with GW. All fetuses with holoprosencephaly had both smaller FACAA (13.99-38.00°, ≤5th percentile) and shorter FACAD (1.6-10.5 mm, ≤5th percentile). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and negative likelihood ratio (LR-) of FACAA for the prediction of holoprosencephaly in fetuses with an intracranial malformation were 100% (95% confidence interval [CI]: 89.3-100.0%), 100% (95% CI: 87.4-100.0%), 100% (95% CI: 89.3-100%), 97.1% (95% CI: 82.9-99.8%), and 0, respectively. The sensitivity, specificity, PPV, NPV, and LR- of FACAD for the prediction of holoprosencephaly in fetuses with an intracranial malformation were 97.6% (95% CI: 85.9-99.9%), 100% (95% CI: 87.0-100.0%), 100% (95% CI: 89.3-100%), 97.1% (95% CI: 82.9-99.8%), and 0.02 (95% CI: 0.003-0.165), respectively. CONCLUSION: FACAA and FACAD are sensitive, easy-to-measure indicators for the prenatal identification of holoprosencephaly, even in early pregnancy. These indices provide objective assessment tools for the diagnosis of fetuses with holoprosencephaly. TRIAL REGISTRATION: Not applicable.

Congenital diaphragmatic hernia (CDH) diagnosed in the first or early second trimester is exceedingly rare. We herein present a unique case of Emanuel syndrome identified through early sequential findings of increased nuchal translucency (NT) and CDH. A 34-year-old Japanese woman was referred at 14 weeks of gestation because of an elevated NT of 3.9 mm detected at 12 weeks, with no other markers of aneuploidy. At 15+1/7 weeks, an ultrasound revealed right-sided heart displacement, a tubular structure near the heart, and a cystic structure on the left, presumed to be the stomach and intestines, respectively-findings indicative of CDH. Fetal karyotyping via amniocentesis confirmed Emanuel syndrome with a karyotype of 47,XY,+der(22) t(11;22)(q23.3;q11.2). This case suggests that early detection of increased NT could lead to the early diagnosis of CHD, which, in our case, was part of Emanuel syndrome.

The ectopic posterior pituitary represents a rare congenital malformation attributable to aberrant embryogenesis of the neurohypophysis. Although it may occur as an isolated anomaly, it is frequently concomitant with other congenital malformations of the central nervous system. Despite extensive investigations, the precise etiology remains elusive; however, accumulating evidence suggests that its pathogenesis may parallel that of septo-optic dysplasia, thereby implicating a genetic predisposition. Earlier accounts predominantly attributed this anomaly to traumatic mechanisms. In contrast, contemporary studies increasingly support a hereditary basis. In this report, we delineate the magnetic resonance imaging (MRI) characteristics of an isolated ectopic posterior pituitary, incidentally discovered during an ataxia work-up in a 72-year-old female patient. Notably, the patient exhibited no clinical evidence of growth hormone deficiency or hyperprolactinemia.