OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up. METHODS: A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis. RESULTS: In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001). CONCLUSION Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.
Female ; Pregnancy ; Humans ; Holoprosencephaly ; Prenatal Diagnosis/methods* ; Central Nervous System ; Fetus/abnormalities* ; Nervous System Malformations/genetics* ; Microarray Analysis ; Central Nervous System Diseases ; Cysts ; Chromosome Aberrations ; Ultrasonography, Prenatal/methods*

BACKGROUNDEvaluation of fetal central nervous system (CNS) agenesis by ultrasonography (US) is frequently limited, but magnetic resonance imaging (MRI) has its own advantages and is gaining popularity in displaying suspected fetal anomalies. The purpose of this study was to explore the value of MRI in detecting fetal CNS agenesis.

METHODSThirty-four women (aged from 22 to 35 years, average 27 years) with complicated pregnancies (16 - 39 weeks of gestation, average 30 weeks) were examined with a 1.5 T superconductive MR unit within 24 hours after ultrasonography. Half-Fourier acquisition single-shot turbo spin-echo (HASTE) T(2)-weighted imaging (T(2)WI) sequence were performed in all patients, and fast low angle shot (FLASH) T(1)-weighted imaging (T(1)WI) sequence were applied sequentially in seven of them. Comparison of the results was made between the MRI and US findings as well as autopsy or postnatal follow-up MRI findings.

RESULTSThe gyrus, sulcus, corpus callosum, thalamus, cerebellum, brainstem, and spinal cord of fetus were shown more clearly on T(2)-weighted MR images than on T(1)-weighted MR images. MRI corrected the diagnosis of US in 10 cases (10/34, 29.41%) and the diagnosis was missed only in 1 case (1/34, 2.94%).

CONCLUSIONMRI has advantages to US in detecting fetal CNS anomalies and is a supplement to US in complicated pregnancies.

Adult ; Central Nervous System ; abnormalities ; diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Pregnancy ; Ultrasonography, Prenatal

The causes of congenital hydrocephalus vary widely and have an important effect in determining the future counseling of affected cases. We analyzed the postmortem findings of 49 autopsies diagnosed as hydrocephalus to find the causes and related conditions. The cases were collected during the last 10 years (1981-1990). The cases consisted of 25 cases associated with various congenital malformations of the central nervous system (CNS), 14 cases of posthemorrhagic hydrocephalus, 4 cases of postinfection hydrocephalus, and 2 cases of hydranencephaly. Four cases were associated with supracerebellar arachnoid cyst (1) and unknown causes (3). Twenty-five cases associated with congenital malformation of the CNS consisted of 10 cases of holotelencephaly, 5 cases of stenosis of the Sylvian aqueduct, 4 cases of agenesis of the corpus callosum, and 3 cases each of Dandy-Walker malformation and Arnold-Chiari malformation. Various malformations of other organs were associated with these cases. Cardiovascular malformations were common, consisting of 11 cases of patent ductus arteriosus (PDA), 7 cases of atrial septal defect (ASD), and 6 cases of patent foramen ovale (PFO). Among the anomalies of the respiratory system, abnormal lobation was commonly associated, as well as hypoplasia of the lung. Gastrointestinal malformations included Meckel's diverticulum, diaphragmatic hernia, mobile intestine, and midline small liver. Cryptorchidism was the most common malformation in the genitourinary system. Holotelencephaly cases showed multiple craniofacial anomalies, as well as other malformations in the central nervous system. Skeletal malformations included polydactyly, simian crease, and flexion deformity. There were no specific constellations of malformations in these different groups of CNS malformations associated with hydrocephalus.
*Abnormalities, Multiple/pathology ; Autopsy ; Central Nervous System/abnormalities ; Cerebral Hemorrhage/complications ; Female ; Fetal Diseases ; Herpes Simplex/complications ; Humans ; Hydrocephalus/complications/embryology/*etiology/pathology ; Infant, Newborn ; Male

OBJECTIVE: To evaluate demographic characteristics of children with suspected dysphagia who underwent videofluoroscopic swallowing study (VFSS) and to identify factors related to penetration or aspiration. METHODS: Medical records of 352 children (197 boys, 155 girls) with suspected dysphagia who were referred for VFSS were reviewed retrospectively. Clinical characteristics and VFSS findings were analyzed using univariate and multivariate analyses. RESULTS: Almost half of the subjects (n=175, 49%) were under 24 months of age with 62 subjects (18%) born prematurely. The most common condition associated with suspected dysphagia was central nervous system (CNS) disease. Seizure was the most common CNS disorder in children of 6 months old or younger. Brain tumor was the most important one for school-age children. Aspiration symptoms or signs were the major cause of referral for VFSS in children except for infants of 6 months old or where half of the subjects showed poor oral intake. Penetration or aspiration was observed in 206 of 352 children (59%). Subjects under two years of age who were born prematurely at less than 34 weeks of gestation were significantly (p=0.026) more likely to show penetration or aspiration. Subjects with congenital disorder with swallow-related anatomical abnormalities had a higher percentage of penetration or aspiration with marginal statistical significance (p=0.074). Multivariate logistic regression analysis revealed that age under 24 months and an unclear etiology for dysphagia were factors associated with penetration or aspiration. CONCLUSION: Subjects with dysphagia in age group under 24 months with preterm history and unclear etiology for dysphagia may require VFSS. The most common condition associated with dysphagia in children was CNS disease.
Brain Neoplasms ; Central Nervous System ; Central Nervous System Diseases ; Child* ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Deglutition Disorders ; Deglutition* ; Fluoroscopy ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Logistic Models ; Medical Records ; Multivariate Analysis ; Pediatrics ; Pneumonia, Aspiration ; Pregnancy ; Referral and Consultation ; Retrospective Studies ; Seizures

Epidermal nevus syndrome is now delineated as a congenitally acquired syndrome consisting of deformities of the skin (various linear epidermal or organoid nevi), central nervous system, skeleton, cardiovascular system, and renal system. A 4-year-old girl had linear epidermal nevus on the right lower extremity, right ear lobe and anterior neck, and multiple skeletal abnorrnalities since birth. And she had an adult fist-sied, soft, nontender mass on the right lower abdomen since 2 years of age. Radiologic examination showed scoliosis of the thoracic spines, deformities of the lumbar spines, focal gigantisms of the left hand and right foot, and other skeletal abnormalities. Histological examination of the linear, verrucous lesion of the right leg showed hyperkeratosis and papillomatosis. The surgically removed abdominal mass revealed the finding of hydrosalpinx.
Abdomen ; Adult ; Cardiovascular System ; Central Nervous System ; Child, Preschool ; Congenital Abnormalities ; Ear ; Female ; Foot ; Hand ; Humans ; Leg ; Lower Extremity ; Neck ; Nevus* ; Organoids ; Papilloma ; Parturition ; Scoliosis ; Skeleton ; Skin ; Spine

OBJECTIVETo assess the state of the art of fetal magnetic resonance imaging (MRI) in China.

DATA SOURCESBoth Chinese and English language literatures were searched in the databases of PUBMED (1998-2005) and CNKI (1998-2005), 41 published articles about fetal MRI were selected.

RESULTSFetal MRI can serve as an adjunct tool for ultrasonography because of its excellent soft tissue contrast, high spatial resolution, multiplanar capabilities, large field of view and simultaneous visualization of fetal and maternal structures. Since the development of ultrafast MRI sequences provides faster scan time and avoids motion artifacts, it is widely applied in detecting normal or abnormal fetal development, including the central nervous system, thoracic region, abdomen and others. In China, experience in fetal MRI has been scanty, but the technique will be extensively used in the near future because of its multi-faceted advantages.

CONCLUSIONSCompared with ultrasonography, MRI as a complementary imaging for fetal screening is prospective in China or other parts of the world because of its multiple superiorities.

Abdomen ; abnormalities ; embryology ; Cell Movement ; Central Nervous System ; abnormalities ; embryology ; Congenital Abnormalities ; diagnosis ; Female ; Fetus ; anatomy & histology ; Humans ; Magnetic Resonance Imaging ; methods ; Myelin Sheath ; physiology ; Pregnancy ; Thorax ; abnormalities ; embryology

BACKGROUNDUsually, cavernous dural arteriovenous fistula can be treated via transarterial approaches. However, in many complicated patients, transvenous approaches are superior to the transarterial ones because of the difficulties during a transarterial operation. In this study, we retrospectively analyzed the outcomes of 28 patients with cavernous dural arteriovenous fistula treated by transvenous embolization.

METHODSFrom September 2001 to December 2005, 28 patients with 31 cavernous dural arteriovenous fistulae were treated with transvenous embolization in Beijing Tiantan Hospital. The involved cavernous sinuses were catheterized via the femoral vein-inferior petrosal sinus approach or the femoral-facial-superior ophthalmic vein approach, and embolized with coils (GDC, EDC, Matrix, Orbit or free coil) or coils plus silk. The patients were followed up for 3 to 26 months.

RESULTSAll the 31 cavernous sinuses in the 28 patients were successfully embolized. Complete angiographic obliteration of the fistulae was achieved immediately in 25 patients. Residual shunting was observed in the other 3, who had drainage through the pterygoid plexus (2 patients) or the inferior petrosal sinus (1) after the operation. Headache and vomiting were the most common symptoms after the embolization. In 3 patients, who achieved complete angiographic obliteration immediately, the left oculomotor nerve palsy remained unchanged after the operation. Transient abducens nerve palsy was encountered in 1. In 1 patient, the occular symptoms were improved after the operation, but recurred 4 days later, and then disappeared spontaneously after 5 days. During the follow-up, no patient had recurrence. Three months after the operation, angiography was performed on the 3 patients with residual shunting. Two of them had angiographic cure, the other had residual drainage through the pterygoid plexus.

CONCLUSIONSTransvenous catheterization and embolization of the cavernous sinus is a safe and efficient way to treat complicated cavernous dural arteriovenous fistulae. It is an alternative to the patients with spontaneous cavernous dural arteriovenous fistulae or those in whom transarterial embolization failed.

Adult ; Aged ; Cavernous Sinus ; abnormalities ; Central Nervous System Vascular Malformations ; complications ; therapy ; Embolization, Therapeutic ; methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVEThere is a paucity of published works that systematically evaluate gene anomalies or clinical features of patients with renal cysts and diabetes syndrome (RCAD)/maturity onset diabetes of the young type 5 (MODY5). The purpose of this review was to systematically assess the detection rate, genetic and phenotypic implications of heterozygous autosomal dominant TCF2 anomalies.

DATA SOURCESMEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germline TCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification (hypomethylation and hypermethylation), loci associated with cancer risk, and somatic TCF2 anomalies were all excluded.

STUDY SELECTIONAfter searching the literature, 50 articles were selected.

RESULTSThe detection rate of TCF2 anomalies was 9.7% and varied considerably among MODY (1.4%), renal structure anomalies (RSA) (21.4%) and RSA with MODY (41.2%) subgroups. Mutations were strikingly located within the DNA binding domain and varied among exons of the DNA binding domain: exons 2 and 4 were the hottest spots, while mutations were sporadically distributed in exon 3. The consistent phenotypes were RSA (89.6%) and diabetes mellitus (DM) (45.0%). However, the concurrence of RSA and DM was relatively low (27.5%), which hinders the optimal performance of genetic testing and obtainment of timely diagnosis. Other organ involvements were complementary and necessary for the early identification of patients with TCF2 anomalies. Analysis of phenotypes of TCF2 point mutations showed significant differences in the detection rates of RSA, impaired renal function (IRF) and DM according to mutation type but not mutation location.

CONCLUSIONThese valuable features of TCF2 anomalies that previously did not receive sufficient attention should not be neglected.

Central Nervous System Diseases ; metabolism ; Dental Enamel ; abnormalities ; metabolism ; Diabetes Mellitus ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Hepatocyte Nuclear Factor 1-beta ; metabolism ; Humans ; Kidney Diseases, Cystic ; metabolism

PHACE association is a rare neurocutaneous condition in which facial hemangiomas associate with a spectrum of posterior fossa malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, and eye anomalies. We reported a case of PHACE association in a premature infant showing facial, intracranial, and oropharyngeal hemangiomas with evidence of the Dandy-Walker variant and complicated cardiovascular anomalies, including a right-sided aortic arch and an atypical patent ductus arteriosus arising from a tortuous left subclavian artery. To our knowledge, intracranial hemangiomas are rare in PHACE association, and a concomitant oropharyngeal hemangioma has not been previously reported in the PHACE association literature. In infants presenting with large, plaque-like facial hemangiomas, it is important to conduct active cardiovascular and neurological evaluations. Special attention should be given to the laryngoscopic examination to search for additional hemangiomas in the airway.
Aorta, Thoracic ; Aortic Coarctation ; Ductus Arteriosus, Patent ; Eye ; Eye Abnormalities ; Hemangioma ; Hemangioma, Cavernous, Central Nervous System ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Neurocutaneous Syndromes ; Subclavian Artery

BACKGROUND: Median cleft lip is a rare anomaly consisting of a midline vertical cleft through the upper lip. It can also involve the premaxillary bone, the nasal septum, and the central nervous system. In our current report, we present the clinical features of 6 patients with a median cleft lip and their surgical management according to the accompanying anomalies. METHODS: From December 2010 to January 2014, 6 patients with a median cleft lip were reviewed. Five of these cases underwent surgical correction; alveolar bone grafting was performed in a patient with a median alveolar cleft. The surgical technique included inverted-U excision of the upper lip and repair of the orbicularis oris muscle. The mean follow-up period was 20.4 months (range, 7.4-44.0 months). RESULTS: The study patients presented various anomalous features. Five patients received surgical correction, 4 with repair of the median cleft lip, and one with iliac bone grafting for median alveolar cleft. A patient with basal sphenoethmoidal meningocele was managed with transoral endoscopic surgery for repair of the meningocele. Successful surgical repair was achieved in all cases with no postoperative complications. CONCLUSIONS: Relatively mild forms of median cleft lip can be corrected with inverted-U excision with good aesthetic outcomes. In addition, there is a broad spectrum of clinical features and various anomalies, such as nasal deformity, alveolar cleft, and short upper frenulum, which require close evaluation. The timing of the operation should be decided considering the presence of other anomalies that can threaten patient survival.
Alveolar Bone Grafting ; Bone Transplantation ; Central Nervous System ; Cleft Lip* ; Congenital Abnormalities ; Follow-Up Studies ; Humans ; Lip ; Meningocele ; Nasal Septum ; Postoperative Complications