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Radiol Case Rep 2021 Jun 17;16(6):1511-1513. Epub 2021 Apr 17.

Department of radiology, Cantonal Hospital "Dr. Safet Mujic," Mostar, Bosnia and Herzegovina.

A fetus with suspicion for holoprosencephaly and various brain malformations were seen on ultrasound and send for magnetic resonance imaging (MRI). Immediately after the birth of the female patient ultrasound and MRI was made which confirmed lobar holoprosencephaly. Fetal MRI stands out as a powerful diagnostic tool for detecting anomalies and other disorders. Read More

Eur J Obstet Gynecol Reprod Biol 2021 May 15;260:64-69. Epub 2021 Mar 15.

Department of Obstetrics and Gynecology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.

Cantrell's pentalogy is a congenital multiple malformation consisting of midline supraumbilical thoraco-abdominal wall defects, anterior and pericardial diaphragm defects, lower sternum defects, ectopia cordis and various intracardiac anomalies. Complete pentalogy is very rare. Some additional anomalies may accompany pentalogy and there are cases in the literature where chromosomal anomalies and pentalogy are seen. Read More

J Clin Ultrasound 2021 Jul 5;49(6):632-635. Epub 2021 Feb 5.

Department of Perinatology, Etlik Zübeyde Hanım Women's Health Care Training and Research Hospital, University of Health Sciences, Ankara, Turkey.

Proboscis lateralis is a very rare congenital craniofacial malformation characterized by a finger-like tubular appendage arising usually from the medial canthal region. It is mostly unilateral and associated with other craniofacial malformations. Occasionally, proboscis lateralis is seen with holoprosencephaly. Read More

Clin Anat 2021 Feb 2. Epub 2021 Feb 2.

Department of Medical Biology, Sections Clinical Anatomy & Embryology, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Netherlands.

Shared anomalies, always located close to the area of coalescence and observable in virtually every type of conjoined twinning, are currently seen as separate anomalies caused by mostly unknown and seemingly unrelated pathways rather than being connected to the twinning mechanism itself. Therefore, most (case) reports about conjoined twins are mere descriptions of (external) dysmorphologies lacking reflections on the possible origin of their concomitant anomalies. As we will demonstrate in this article, shared anomalies are influenced, and in some cases solely and sequentially explained, by interaction aplasia and neo-axial orientation; two embryological mechanisms to which each set of conjoined twins is subjected and are responsible for their ultimate phenotypical fate. Read More

J Matern Fetal Neonatal Med 2021 Jan 17:1-9. Epub 2021 Jan 17.

Feto-Maternal Medicine, University Hospitals, Leuven, Belgium.

Objective: Middle interhemispheric (MIH) variant of holoprosencephaly (HPE) or syntelencephaly is a rare prosencephalic cleavage disorder. In literature, few cases of accurate prenatal diagnosis have been reported. We report on four additional prenatally diagnosed cases. Read More

Pediatr Radiol 2020 12 30;50(13):1934-1947. Epub 2020 Nov 30.

Department of Radiology, Boston Children's Hospital, 300 Longwood Ave., Boston, MA, 02115, USA.

Fetal MRI is the modality of choice to study supratentorial brain malformations. To accurately interpret the MRI, the radiologist needs to understand the normal sequence of events that occurs during prenatal brain development; this includes familiarity with the processes of hemispheric cleavage, formation of interhemispheric commissures, neuro-glial proliferation and migration, and cortical folding. Disruption of these processes results in malformations observed on fetal MRI including holoprosencephaly, callosal agenesis, heterotopic gray matter, lissencephaly and other malformations of cortical development (focal cortical dysplasia, polymicrogyria). Read More

J Child Neurol 2021 Apr 23;36(5):357-364. Epub 2020 Nov 23.

Division of Neurology, 2518Cincinnati Children's Hospital, Cincinnati, OH, USA.

Holoprosencephaly is the most common malformation of forebrain development and includes a wide spectrum of severity. The objective of this retrospective study was to evaluate fetal magnetic resonance imaging (MRI) associations with outcome. Of the 63 cases identified on antenatal ultrasonography, 28 cases were confirmed on fetal MRI. Read More

Am J Obstet Gynecol 2020 12 7;223(6):B13-B16. Epub 2020 Nov 7.

Am J Obstet Gynecol 2020 12 7;223(6):B23-B26. Epub 2020 Nov 7.

Am J Obstet Gynecol 2021 04 27;224(4):396.e1-396.e15. Epub 2020 Oct 27.

Department of Ultrasound, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China. Electronic address:

Background: First-trimester ultrasound scans were introduced to China for nearly 20 years. The ability of first-trimester ultrasound screening to detect different malformations was variable. A recent systematic review concluded that the use of a standardized anatomic protocol was the most crucial factor to improve the sensitivity of first-trimester ultrasound screening for anomalies. Read More

Mymensingh Med J 2020 Oct;29(4):1010-1014

Dr Manifa Afrin, Assistant Professor, Department of Pediatrics, BIHS General Hospital, Mirpur, Dhaka, Bangladesh; E-mail:

Holoprosencephaly is a rare spectrum of congenital malformation associated with midline facial defects and absence of olfactory tract. Sequence occurs at 4th to 8th week of gestational age due to failure or incomplete diverticulation and cleavage of primitive prosencephalon. It is most common brain malformation with an incidence 1:250 in conceptuses and associated with a high rate of spontaneous abortion, and prevalence of 1:16000 in live borns. Read More

Ultrasound Obstet Gynecol 2021 Feb;57(2):204-214

Department of Medicine and Surgery, Unit of Surgical Sciences, Obstetrics and Gynecology, University of Parma, Parma, Italy.

Most brain abnormalities are present in the first trimester, but only a few are detected so early in gestation. According to current recommendations for first-trimester ultrasound, the fetal head structures that should be visualized are limited to the cranial bones, the midline falx and the choroid-plexus-filled ventricles. Using this basic approach, almost all cases of acrania, alobar holoprosencephaly and cephalocele are detected. Read More

J Vet Intern Med 2020 Nov 3;34(6):2682-2686. Epub 2020 Oct 3.

Department of Medical Sciences, University of Wisconsin - Madison, Madison, Wisconsin, USA.

Case Description: A 10-month-old neutered male mixed breed dog was presented for assessment of poorly controlled seizures.

Clinical Findings: Magnetic resonance imaging of the brain disclosed complete absence of the lateral and third ventricles and mesencephalic aqueduct. Postmortem computed tomographic (CT) imaging and positive contrast cisterno-ventriculography confirmed the lack of a contiguous ventricular system. Read More

Int J Clin Pediatr Dent 2020 May-Jun;13(3):295-298

Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Montpellier, Montpellier, Cedex 5, France.

Background: The single median incisor is a rare dental abnormality that could be isolated or could be part of many different syndromes or syndromic association with poor prognosis.

Case Description: We report the first prenatal ultrasound description of a 31-year-old patient, gravida 1, para 0, whose male fetus was diagnosed at 25 weeks' gestation with a single median incisor suggestive of nasal pyriform aperture stenosis in Montpellier University Hospital (France). A fetal magnetic resonance imaging (MRI) performed at 30 weeks' gestation retrieved no intracranial midline cerebral anomalies and confirm nasal pyriform aperture stenosis suspicion. Read More

Am J Med Genet A 2020 10 11;182(10):2409-2416. Epub 2020 Aug 11.

Division of Pediatric Otolaryngology, Texas Children's Hospital, Houston, TX, USA.

Agnathia is a rare congenital malformation with unknown etiology characterized by absence of the mandible, microstomia, and tongue aplasia, often found to have other anomalies including holoprosencephaly. The purpose of this paper was to describe the symptoms and imaging of a case of isolated agnathia and to conduct a comprehensive literature review of reported patients with isolated agnathia. Case reports of isolated agnathia are very rare, with most infants as stillborn. Read More

Brain 2020 08;143(8):e65

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA.

Radiographics 2020 Sep-Oct;40(5):1458-1472. Epub 2020 Jul 24.

From the Department of Radiology (S.W.C., S.V.G.) and Department of Obstetrics & Gynecology (B.K.B.), Duke University, 2301 Erwin Rd, Box 3808, Durham, NC 27710.

Fetal central nervous system (CNS) abnormalities are second only to cardiac malformations in their frequency of occurrence. Early and accurate diagnosis at prenatal US is therefore essential, allowing improved prenatal counseling and facilitating appropriate referral. Thorough knowledge of normal intracranial anatomy and adoption of a logical sonographic approach can improve depiction of abnormal findings, leading to a more accurate differential diagnosis earlier in pregnancy. Read More

Brain 2020 08;143(8):e64

Hunter Genetics, Waratah, NSW 2298, Australia.

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 May;37(5):547-550

Department of Gynecology and Obstetrics, Shengjing Hospital Affiliated to China Medical University, Key Laboratory of Maternal Fetal Medicine of Liaoning Province, Shenyang, Liaoning 110004, China.

Objective: To analyze the clinical features and pathogenesis of a fetus with holoprosencephaly.

Methods: The findings of prenatal ultrasonography was reviewed. Following elective abortion, whole exome sequencing (WES) was carried out to identify potential pathogenic variant. Read More

Pediatr Radiol 2020 05 26;50(6):863-868. Epub 2020 Feb 26.

Department of Medical Imaging, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria, 3052, Australia.

Background: Septopreoptic holoprosencephaly is a mild form of holoprosencephaly in which the midline non-separation is restricted to the septal or preoptic regions. This entity has only been described in a small case series in which associated intracranial abnormalities were limited to the midline structures.

Objective: To describe the radiologic findings of septopreoptic holoprosencephaly and highlight that it can be associated with a variety of intracranial abnormalities, not merely with abnormalities restricted to midline structures as previously reported. Read More

J Med Genet 2020 06 3;57(6):389-399. Epub 2020 Feb 3.

Département de Génétique, APHP, Hopital Robert Debré, 75019 Paris, France

Background: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level.

Methods: 7 patients with newly identified mutations in (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions. Read More

Vet Med Sci 2020 08 23;6(3):454-461. Epub 2020 Jan 23.

Department of Veterinary Anatomy and Physiology, University of Nairobi, Nairobi, Kenya.

Background: Holoprosencephaly is a forebrain deformity that results from varying degrees of separation failure of cerebral hemispheres. The condition is classified based on the degree of non-separation of the hemispheres which, in turn, determines its severity. Holoprosencephaly is usually accompanied by craniofacial defects whose severity tends to reflect the extent of brain deformities. Read More

Prenat Diagn 2020 04 10;40(5):565-576. Epub 2020 Feb 10.

Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.

Objective: The objective of this study is to evaluate the prenatal diagnosis, postnatal characteristics, and the spectrum of associated findings in fetuses with holoprosencephaly (HPE).

Methods: Fetal neurosonograms, postnatal assessment, and chromosomal analysis were performed in a cohort of 25 fetuses with HPE.

Results: The prevalence of HPE in high-risk pregnancies was 4. Read More

Am J Med Genet A 2020 03 17;182(3):441-445. Epub 2019 Dec 17.

Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts.

Kabuki syndrome is a rare, multi-systemic disorder of chromatin regulation due to mutations in either KMT2D or KDM6A that encode a H3K4 methyltransferase and an H3K27 demethylase, respectively. The associated clinical phenotype is a direct result of temporal and spatial changes in gene expression in various tissues including the brain. Although mild to moderate intellectual disability is frequently recognized in individuals with Kabuki syndrome, the identification of brain anomalies, mostly involving the hippocampus and related structures remains an exception. Read More

Ultrasound Obstet Gynecol 2020 Nov;56(5):732-739

Academic Unit of Radiology, University of Sheffield, Sheffield, UK.

Objective: To analyze a large retrospective cohort of fetuses in which the cavum septi pellucidi and vergae (CSPV) was not present or was not in its expected position on in-utero magnetic resonance imaging (iuMRI), in order to describe the possible causes of that finding and provide a diagnostic approach to assess such cases in clinical practice using iuMRI.

Methods: This was a retrospective study of fetuses that underwent iuMRI at a single institution, over an 18-year period (2000-2017 inclusive), in which the CSPV was not visualized or was abnormal. All iuMRI studies were reviewed and classified as CSPV being not present, disrupted (visualization of remnants of an otherwise normally placed CSPV) or malpositioned (CSPV was present, but not in its expected position). Read More

Int J Pediatr Otorhinolaryngol 2020 Jan 5;128:109705. Epub 2019 Oct 5.

College of Medicine, The Ohio State University, 370 W 9th Ave, Columbus, OH, USA, 43210.

Background: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of upper airway obstruction in neonates. It can occur either associated with a solitary median maxillary central incisor (SMMCI) in 40-75% of cases or as an isolated morphogenic variant. Brain MRI is routinely performed in patients with CNPAS with a SCMMI due to the concomitant risks of intracranial midline defects of the hypothalamic-pituitary axis (HPA), holoprosencephaly, or associated endocrine dysfunction. Read More

Am J Med Genet A 2019 12 9;179(12):2454-2458. Epub 2019 Sep 9.

Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Cases with multiple molecular diagnoses are challenging to diagnose clinically, yet may be resolved by unbiased exome sequencing analysis. We report an infant with developmental delay, severe growth delay, dysmorphic features, and multiple congenital anomalies including retinal coloboma, congenital pyloric stenosis, and circumferential skin creases. Exome sequencing identified a homozygous missense variant in MAPRE2 and a homozygous stopgain (nonsense) variant in CDON. Read More

J Hum Genet 2019 Nov 16;64(11):1127-1132. Epub 2019 Aug 16.

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.

RAC3 is a member of the Rho GTPases family, which has important regulatory functions in aspects of neuronal morphogenesis. Rho GTPases show a conformational change in two regions (switch I and II) through GTP binding, which provides a platform for selective interactions with functionally diverse proteins. Missense variants in the switch I and II regions of RAC3 were recently suggested to cause severe intellectual disability and brain malformations. Read More

Clin Genet 2019 12 21;96(6):560-565. Epub 2019 Aug 21.

Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.

Meckel syndrome (MKS) is a perinatally lethal, genetically heterogeneous, autosomal recessive condition caused by defective primary cilium formation leading to polydactyly, multiple cysts in kidneys and malformations of nervous system. We performed exome sequencing in six fetuses from six unrelated families with MKS. We identified seven novel variants in B9D2, TNXDC15, CC2D2A, CEP290 and TMEM67. Read More

Ultrasound Obstet Gynecol 2019 Oct;54(4):468-476

Fetal Medicine Research Institute, King's College Hospital, London, UK.

Objective: To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities.

Methods: This was a retrospective study of prospectively collected data from 100 997 singleton pregnancies attending for a routine ultrasound examination of fetal anatomy, performed according to a standardized protocol, at 11-13 weeks' gestation. All continuing pregnancies had an additional scan at 18-24 weeks and 71 754 had a scan at either 30-34 or 35-37 weeks. Read More