Fetal and neonatal outcomes of posterior fossa anomalies: a retrospective cohort study.

The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC), Riyadh. All fetuses diagnosed by prenatal ultrasound with PFA from 2017 to 2021 in KAMC were analyzed retrospectively. PFA included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), and isolated vermian hypoplasia (VH). The 65 cases of PFA were 41.5% DWM, 46.2% MCM, 10.8% VH, and 1.5% BPC. The annual incidence rates were 2.48, 2.64, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value = 0.014) and seizures than others (45% vs. 17.9%; p-value = 0.041). Ten patients with abnormal genetic testing showed a single gene mutation causing CNS abnormalities, including a pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1, and a variant of uncertain significance in the PNPLA8 gene. Our result showed that the most common PFA is DWM and MCM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA.

Relative prevalence and outcome of fetal posterior fossa abnormality.

AIM: To find out the relative incidence and outcome of posterior fossa abnormality (PFA) in terms of survival at birth until 2 years of age. METHODS: We conducted a prospective study; all fetuses diagnosed with posterior fossa abnormality were followed-up. The outcome was observed with respect to survival, the presence of associated anomalies, the existence of developmental delay after a telephonic interview. RESULTS: Out of 2703 children with congenital anomalies, 921 (34.1%) had a central nervous system defect; 76 cases of PFA were fully followed. Dandy-Walker malformation (DWM) was present in 50% (38/76), mega cisterna magna 18.4% (14/76), Blake pouch cyst 13.2% (10/76), vermian hypoplasia (VH) 13.2% (10/76) and arachnoid cyst 5.2% (4/76). The diagnosis was possible before 20 weeks in only 12 (15.8%) cases. The mean gestational age at delivery was 34.7 ± 6.7 weeks. Associated anomalies were seen in 35/76 (46.1%) cases. A total of 35/76 (46.1%) survived after 2 years; there was developmental delay in 9.2% of cases. CONCLUSION: There is a large variation in the outcome of PFA depending upon the type of anomaly. Associated anomalies are common in VH and DWM, making their prognosis worse.

Expanding the spectrum of CEP55-associated disease to viable phenotypes.

Homozygosity for nonsense variants in CEP55 has been associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel-like syndrome. Missense variants in CEP55 have not previously been reported in association with disease. Here we describe seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all have a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings are homozygous for a consensus splice site variant near the end of the gene. These affected girls all have severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. Here we compare our seven patients with three previously reported families with a prenatal lethal phenotype (MARCH syndrome/Meckel-like syndrome) due to homozygous CEP55 nonsense variants. Our series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype. We show that homozygosity for a splice variant near the end of the CEP55 gene is also compatible with life.

Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study.

BACKGROUND: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. OBJECTIVE: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. METHODS: Anonymous individual data on cases of DW malformation diagnosed in 2002-2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. RESULTS: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79-7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08-3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39-3.13). CONCLUSIONS: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.

The Most Common Comorbidities in Dandy-Walker Syndrome Patients: A Systematic Review of Case Reports.

OBJECTIVE: Dandy-Walker syndrome (DWS) is a rare neurologic multi-entity malformation. This review aimed at reporting its main nonneurologic comorbidities. METHODS: Following PRISMA guidelines, search in Medline was conducted (2000-2014, keyword: dandy-walker). Age, sex, country, DWS type, consanguinity or siblings with DWS, and recorded coexistent conditions (by ICD10 category) were extracted for 187 patients (46.5% male, 43% from Asia) from 168 case reports. RESULTS: Diagnosis was most often set in <1 year old (40.6%) or >12 years old (27.8%). One-third of cases had a chromosomal abnormality or syndrome (n = 8 PHACE), 27% had a cardiovascular condition (n = 7 Patent Ductus Arteriosus), 24% had a disease of eye and ear (n = 9 cataract); most common malignancy was nephroblastoma (n = 8, all Asian). Almost one-fifth had a mental illness diagnosis; only 6.4% had mild or severe intellectual disability. CONCLUSION: The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years.

Enlarged posterior fossa on prenatal imaging: differential diagnosis, associated anomalies and postnatal outcome.

INTRODUCTION: The primary aim of this study was to ascertain the prevalence of the individual conditions and of associated anomalies in fetuses with the prenatal diagnosis of enlarged posterior fossa (PF) and to explore the diagnostic accuracy of ultrasound in these anomalies. The secondary aim was to evaluate the postnatal outcome of children affected by PF anomalies. MATERIAL AND METHODS: All fetuses with enlarged PF detected by prenatal sonography at a referral center from 2001 to 2015 were analyzed retrospectively. Some were also studied by fetal magnetic resonance imaging (MRI) or volume ultrasound examinations. Fetal sonographic and MRI were compared using following classification: Dandy-Walker malformation (DWM); megacisterna magna (MCM); Blake's pouch cyst; isolated vermian hypoplasia; vermian agenesis; PF arachnoid cyst (AC); and cerebellar hypoplasia (CH). RESULTS: The ultrasound diagnoses of the 69 fetuses were as follows: MCM (n = 29; of these isolated n = 15), DWM (n = 28, isolated n = 4), vermian hypoplasia (n = 5, isolated n = 4), Blake's pouch cyst (n = 4, isolated n = 1), CH (n = 2; none isolated) and AC in the PF (n = 1, isolated). Thirteen of the 41 karyotyped fetuses were aneuploid, including seven with DWM. Associated malformations were found in 37/69 cases. There were 39 live births, including 11 with confirmed DWM, six of whom show a normal development. Twelve infants with isolated MCM show normal development. There were eight false-positive prenatal diagnoses (or resolution until birth) of "enlarged PF": three with Blake's pouch cyst, two with MCM and one with vermian hypoplasia. CONCLUSIONS: An enlarged PF requires specific diagnoses for the best possible counseling. The term "Dandy-Walker variant" should not be used anymore. Isolated MCM and Blake's pouch cyst can either resolve or be normal variants, but may also indicate the presence of a more severe anomaly or associated malformations.

[Megacisterna magna as incidental finding in a boy with ADHD]. / Megacisterna magna als toevalsbevinding bij een jongen met ADHD.

In this case report we describe how a 13-year-old boy with a complex development profile was diagnosed with adhd and who was also found to have a megacisterna magna, a posterior fossa anomaly in the Dandy-Walker continuum. We searched the literature for reports of other patients who had this (mild) brain anomaly along with psychiatric problems in general and attention problems in particular. Our search of the literature suggested a possible link between the two diagnostic entities.

Brief report pregnancy outcome in women assigned an ICD-9/ICD-9-CM 655.0 code "central nervous system malformation in fetus affecting management of pregnancy": can these codes aid in surveillance for central nervous system defects?

BACKGROUND: The difficulty many birth defects registries have in identifying early pregnancy terminations can lead to significant underreporting of certain types of malformations. This study was designed to determine the potential benefit of using maternal ICD-9 codes relating to management of pregnancy due to fetal anomaly in surveillance of central nervous system (CNS) defects (655.0). METHODS: Women assigned the ICD-9/ICD-9-CM (henceforth termed ICD-9) code 655.0 between 1990 and 2000 were ascertained from two administrative health databases in Manitoba, Canada, one relating to maternal serum screening and one based on hospital discharges. Information was collected on the type of CNS defect identified and whether it was isolated or associated with other anomalies. The relationship of these variables to pregnancy outcome and its potential impact on surveillance for these types of defects was explored. RESULTS: Neural tube defects were the most common finding (67%) identified in the fetuses/infants of women assigned code 655.0, followed by hydrocephaly (20%) and Dandy-Walker anomaly (6%), but the proportion of neural tube defect cases declined after food fortification with folic acid. Termination of pregnancy occurred in ∼50% of neural tube defect cases, 18% before 20 weeks of gestation, but was rare for other CNS defects. CONCLUSION: The maternal ICD-9 code 655.0 had a very high (97%) positive predictive value for identifying fetuses with a CNS defect; 655.00 was particularly effective in identifying neural tube defects pregnancies terminated before 20 weeks gestation that would be difficult to ascertain, especially by passive surveillance systems using infant related data alone.

Diagnóstico prenatal del Síndrome de Dandy-Walker clásico / Prenatal diagnosis of the classic Dandy-Walker's syndrome

Alrededor de 1 por cada 1 000 recién nacidos presenta algún tipo de alteración cráneo encefálica, constituyen el 15 por ciento de todas las malformaciones. El Síndrome de Dandy-Walker constituye el espectro de trastornos, resultantes de un desarrollo anómalo del cerebelo asociado con una alteración en el desarrollo del cuarto ventrículo. Constituye una malformación congénita poco frecuente. Se pretende resaltar la importancia del diagnóstico precoz por ultrasonografía de malformaciones congénitas en el nivel primario de atención médica. Se presenta el diagnóstico prenatal, por ultrasonido, de un caso que a las 20 sem de gestación se le observaron imágenes ecolúcidas en el feto ubicadas a nivel del cerebelo, 4to ventrículo y atrium ventricular lo que hizo sospechar de inmediato en el diagnóstico de un Síndrome de Dandy Walker, sin otra alteración demostrable en este tiempo de embarazo. Previo asesoramiento genético, la pareja decidió la terminación del embarazo. El caso fue confirmado por Anatomía patológica y no se encontraron otras malformaciones asociadas (AU)

Around one by each 1 000 newborns has some type of encephalic skull alteration accounting for the 15 percent of all the malformations. The Dandy-Walker syndrome is the disorder spectrum, resulting from an anomalous cerebellum development associated with an alteration in the four ventricle development. It is an uncommon congenital malformation. Authors try to emphasize on the significance of the ultrasonography in the early diagnosis of congenital malformations at medical care primary level. Authors present the US prenatal diagnosis of a patient that at 20 weeks of pregnancy with fetal echo-lucid images located at cerebellum level, fourth ventricle and ventricular atrium arousing immediate suspect of Dandy-Walker diagnosis without other alterations present at this pregnancy stage. With a previous genetic advice, couple took the decision of end the pregnancy. This case was confirmed by a pathologic anatomy study without other associated malformation (AU)

Use of clomiphene citrate and birth defects, National Birth Defects Prevention Study, 1997-2005.

BACKGROUND: Clomiphene citrate (CC) is the first line drug for subfertility treatment. Studies assessing the association between CC and birth defects have been inconclusive. METHODS: We used data from the National Birth Defects Prevention Study, a population-based, multi-site case-control study of major birth defects. Women from 10 US regions with deliveries affected by at least one of >30 birth defects (cases) and mothers of live born infants without a major birth defect (controls) who delivered October 1997-December 2005 were interviewed. The exposure of interest was reported CC use in the period from 2 months before conception through the first month of pregnancy. Women who conceived using assisted reproductive technology were excluded. Thirty-six birth defect categories with at least three exposed cases were studied. Multiple logistic regression was used to control for potential confounders. RESULTS: CC use was reported by 1.4% of control mothers (94/6500). Among 36 case-groups assessed, increased adjusted odds ratios (aOR) were found [all: aOR, 95% confidence interval (CI)] for anencephaly (2.3, 1.1-4.7), Dandy-Walker malformation (4.4, 1.7-11.6), septal heart defects (1.6, 1.1-2.2), muscular ventricular septal defect (4.9, 1.4-16.8), coarctation of aorta (1.8, 1.1-3.0), esophageal atresia (2.3, 1.3-4.0), cloacal exstrophy (5.4, 1.6-19.3), craniosynostosis (1.9, 1.2-3.0) and omphalocele (2.2, 1.1-4.5). CONCLUSIONS: Several associations between CC use and birth defects were observed. However, because of the small number of cases, inconsistency of some findings with previous reports, and the fact that we cannot assess the CC effect separately from that of the subfertility, these associations should be interpreted cautiously.

Síndrome de Danly-Walker. Comunicación de dos casos y revisión / Dandy-Walker síndrome. A report of two cases and review

Las malformaciones quísticas de la fosa posterior en el recién nacido son de gran interés, en particular las correspondientes al espectro malformativo de Dandy-Walker. El síndrome de Dandy-Walker es una malformación de la fosa posterior que se caracteriza por diferentes grados de dilatación del cuarto ventrículo, hipoplasia del vermis cerebeloso y megacisterna magna asociada con frecuencia a hidrocefalia congénita. La etiología es heterogénea y más frecuente en el sexo femenino. Las manifestaciones clínicas suelen evidenciarse desde la infancia y pueden acompañarse de otras malformaciones congénitas externas y del sistema nervioso central. El tratamiento es la derivación de los ventrículos. Se comunican dos casos de síndrome de Dandy-Walker con una presentación y evolución clínica muy distinta y hacemos unas consideraciones generales de interés sobre esta afección (AU)

Cystic malformations of the posterior cranial fosse in the newborn are of great interest, especially those related to the Dandy-Walker malformation range. The Dandy-Walker syndrome is a posterior cranial fosse malformation characterized by several degrees of cystic dilation of the fourth ventricle, cerebellar vermian hypoplasia and megacisterna magna frequently associated with congenital hydrocephalus etiology is heterogeneous and it´s more frequent in females. Clinical manifestations are present since infancy and could be associated to other external and central nervous system congenital malformations. Treatment consists of ventricle shunt. We present two cases of Dandy-Walker Syndrome with different presentation and evolution and we discuss different aspects of this clinical condition (AU)

Racial disparities in mortality among infants with Dandy-Walker syndrome.

BACKGROUND: Congenital malformations are the major cause of infant mortality in the United States, but their contribution to overall racial disparity--a major public health concern--is poorly understood. We sought to estimate the contribution of a congenitally acquired central nervous system lesion, Dandy-Walker Syndrome (DWS), to black-white disparity in infant mortality. METHODS: Data were obtained from the New York State Congenital Malformations Registry, an ongoing population-based validated surveillance system. We compared black to white infants with respect to infant, neonatal, and postneonatal mortality using Cox proportional hazards regression models. RESULTS: A total of 196 live-born neonates were diagnosed with DWS in the state from 1992 to 2005 inclusive. Of these, 53 were non-Hispanic black and 76 were non-Hispanic white. Neonatal mortality was similar for non-Hispanic blacks and non-Hispanic whites (adjusted hazards ratio [AHR], 1.42; 95% CI, 0.52-3.82), but non-Hispanic blacks had an 8-fold increased risk for postneonatal mortality (AHR, 8.26; 95% CI, 2.08-32.72). Adjustment for fetal growth and other maternal and infant characteristics resulted in a 10-fold increased risk of mortality for non-Hispanic black infants as compared to non-Hispanic whites. By contrast, adjustment for preterm birth attenuated the risk, but non-Hispanic black infants were still more than 6 times as likely to die during the postneonatal period than non-Hispanic whites (AHR, 6.36, 95% CI, 1.52-26.60). CONCLUSION: DWS has one of the largest black-white disparities in postneonatal survival. This underscores the importance of evaluating racial disparities in infant mortality by specific conditions in order to formulate targeted interventions to reduce disparities.

Developmental outcome of children with enlargement of the cisterna magna identified in utero.

An enlarged cisterna magna can be identified during routine ultrasound screening in the second half of pregnancy. It is important to be able to give an accurate prognosis. We evaluated the developmental outcome of these children. A total of 29 fetuses with a large cisterna magna identified in utero were compared to 35 children with a normal fetal ultrasound. The children were evaluated by the Gesell Developmental Schedules and the Peabody Developmental Motor Scale. The study group showed a significantly worse performance in the Gesell test. However, the overall performance for both groups was within normal limits. Four children in the study group had a borderline developmental quotient. Both groups performed similarly in the Peabody test. Walking age was significantly delayed in the study group. Children with an enlarged cisterna magna may be at risk for mild developmental delay. In cases of nonisolated enlargement of the cisterna magna, the outcome may be guarded.

Dandy-Walker syndrome and monochorionic twins: insight into a possible etiological mechanism.

OBJECTIVE: Dandy-Walker syndrome (DWS) is a developmental malformation of the central nervous system characterized by complete or partial absence of the cerebellar vermis, the presence of a posterior fossa cyst, and ventriculomegaly. Although DWS can be seen with Mendelian and chromosomal disorders, the actual pathophysiologic mechanism responsible for the syndrome is unknown. The incidence of DWS is approximately 1-8/100,000 births. We have noted a higher than expected incidence of DWS in a population of twins referred as complicated monochorionic twins, to include twin-twin transfusion syndrome (TTTS). The purpose of this study was to assess the incidence of DWS in monochorionic twins. METHODS: The database of all patients referred with complicated monochorionic twins was queried for the diagnosis of DWS. TTTS was defined sonographically as the combined presence of a maximum vertical pocket (MVP) of >or=8 cm in the recipient and

The Dandy-Walker variant: a case series of 24 pediatric patients and evaluation of associated anomalies, incidence of hydrocephalus, and developmental outcomes.

OBJECT: The Dandy-Walker complex is a continuum of aberrant development of the posterior fossa that has been associated with multiple congenital anomalies, radiographic abnormalities, and developmental delay. The Dandy-Walker variant (DWV) is a unique entity believed to represent a milder form of the complex, and is characterized by a specific constellation of radiographic findings. In this retrospective case series, the authors report the association of the DWV with other congenital anomalies, the associated radiographic findings linked with DWV, and the developmental outcome in this population. METHODS: The charts and radiographs of 10 male and 14 female patients treated between 2000 and 2006 were examined. The patients' mean gestational age was 35.6 weeks (range 23-41 weeks), and the mean follow-up period was 5.1 years (range 1 month-15 years). RESULTS: Three patients died. Associated anomalies included cardiac (41.7%), neurological (33.3%), gastrointestinal (20.8%), orthopedic (12.5%), and genitourinary (12.5%) abnormalities. Less common were pulmonary and psychiatric findings. Developmental delay was identified in 11 of the 21 patients for whom follow-up was available. Five of 6 patients with isolated DWV had a normal developmental course. Radiographic findings associated with DWV included corpus callosum dysgenesis in 20.8%, ventricular enlargement in 29%, and vermian rotation in 8.3%. Shunts were placed in 4 of 7 patients with ventriculomegaly. Using the two-tailed Pearson correlation, the authors determined that developmental outcome was solely affected by neurological deficits and that ventricular enlargement predicted the need for shunt placement. CONCLUSIONS: The DWV was associated with both extra- and intracranial anomalies. Associated radiographic abnormalities including ventriculomegaly were observed. Hydrocephalus requiring cerebrospinal fluid diversion may be indicated. Isolated DWV was associated with a good developmental outcome.

Congenital malformations of the central nervous system: clinical approach.

Central nervous system (CNS) malformations represent important factor of morbidity and mortality in children. The aim of the study was to determine the incidence, type and clinical features of CNS malformations in children who were admitted at the Neonatal and Child Neurology Department, Neonatal Intensive Care Unit and Paediatric Intensive Care Unit of Paediatric Clinic, University of Sarajevo Clinics Centre, from January 1st, 2002 to December 31st, 2006. There were total of 16520 admissions at the Paediatric Clinic over the studied period. CNS malformations, solitary or multiple, have been diagnosed in 100 patients (0,61%). The total number of various CNS malformations was 127. Lethal outcome was established in 9/100 cases (9%). The most frequent CNS malformations were neural tube defects 49/127 (38,6%). Hydrocephalus was seen in 34/127 (26,8%), microcephaly in 24/127 (18,9%), agenesis of corpus callosum in 10/127 (7,9%), Dandy Walker malformation in 6/127 (4,7%) and other CNS malformations in 4/127 (3,1%). In 20/100 of patients neural tube defect was associated with hydrocephalus (20%). CNS malformations were prenatally diagnosed in 13/100 of patients (13%). Primary prevention of CNS malformations can be improved in our country by better implementation of preconceptional folic acid therapy for all women of childbearing age. Secondary prevention by prenatal diagnosis requires advanced technical equipment and adequate education of physicians in the field of foetal ultrasonography. In our circumstances, prenatal diagnostics of CNS malformations is still not developed enough.

Parenchymal neurocutaneous melanosis in association with intraventricular dermoid and Dandy-Walker variant: a case report.

Neurocutaneous melanosis (NCM) is a rare congenital disease that is characterized by the presence of large or multiple congenital melanocytic nevi and melanotic lesions of the central nervous system. We report here on the CT and MR imaging findings of an unusual case of NCM that was associated with intraventricular dermoid and Dandy-Walker malformation.