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Child Health Research Institute Pediatric Research Forum Children’s Hospital & Medical Center

5-2021

Postnatal Diagnosis of Dandy Walker Malformation with Encephalocele

Heerali Patel

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Part of the Pediatrics Commons Postnatal Diagnosis of Dandy Walker Malformation with Encephalocele

Heerali Patel, M2; Julie Sundermeier, NNP; Terence Zach, MD Creighton University School of Medicine, Omaha, NE

Case Presentation Discussion

A female preterm was born at 36 weeks’ gestation by repeat Encephalocele Cesarian section. Birth weight was 2500 g, 21st percentile for gestational age. Head circumference was 34.5 cm, 91st percentile Encephalocele is a defect of the neural tube. It is most common in for gestational age (6). The pregnancy was complicated by poorly the occipital region but occasionally may be present anteriorly (3). controlled maternal diabetes. The mother’s hemoglobin A1c was The condition is characterized by a protrusion of tissue, 7% early in pregnancy. A prenatal ultrasound at 16 weeks’ meninges, or (CSF) through an opening in the gestation demonstrated an anomaly of the central , (10). described as an occipital encephalocele. Amniocentesis revealed Most cases of encephaloceles are congenital, with some cases normal chromosomes. secondary to tumors, trauma, or iatrogenic injury. The cause of the At birth, APGAR scores at 1 minute and 5 minutes were both 8. A defect is due to incomplete separation between surface ectoderm 4.5 by 5 cm occipital encephalocele encapsulated with skin and no and neuroectoderm after closure of the neural folds by day 25 in open areas was present (Figure 1). The infant had polydactyly of the embryo. Facial deformities, including hypertelorism, may occur. the right thumb (Figure 2), otherwise there were no other Figure 1 Encephalocele Encapsulated with Skin is present in 40-60% of cases (3). dysmorphic features. Encephalocele occurs in 0.8-5.6 out of every 10,000 live births MRI showed strands of linear soft tissue within the defect but no (10). It comprises 15%-20% of all neural tube defects. Occipital frank herniation of cerebellar or cerebral contents within the encephaloceles are predominantly seen in females; males have a encephalocele. Imaging also showed an intraventricular higher association with anterior encephaloceles (3). hemorrhage in the right atrium and occipital horn with Most cases of encephaloceles are identified with prenatal ventriculomegaly of the right lateral ventricle. A Dandy Walker ultrasound. Postnatal MRI is recommended to determine the malformation was also present. (Figures 3-5) amount of neural tissue within the encephalocele and whether Renal ultrasound was normal. other brain anomalies are present (3, 7). Her neurologic exam was appropriate for her gestational age. Surgical closure of the dura and removal of non-functional tissue is imminent with skin ulceration or CSF leakage (3). Buccal samples for whole exome sequencing by microarray analysis did not reveal any variants of known clinical significance. Dandy Walker Malformation Two variants of unknown significance and one likely pathogenic Dandy Walker malformation (DWM) is a defect involving agenesis variant were identified. The variants of unknown significance were or hypoplasia of the cerebellar vermis, cystic dilation of the fourth paternally inherited point mutations in the MBD5 and CEP290 Figure 2 Polydactyly of Right Thumb ventricle, and enlargement of the posterior fossa (11). The genes. A deletion in the ACY1 gene was maternally inherited and ventricular dilation causes superior displacement of the lateral indicated as likely pathogenic. sinus, tentorium, and torcula (4, 15). An occipital encephalocele repair with placement of a The pathogenesis of DWM may be related to deletions of genes ventriculoperitoneal shunt and cranioplasty was performed at 18 ZIC1 and ZIC4 that are involved in cerebellar development (1). days of age. The infant was discharged on day 46. Mutations in these genes were not present in our patient, as confirmed by exome sequencing. DWM occurs in 1 out of every 25,000-35,000 live births, References predominantly in females. DWM is also associated with other extracranial anomalies, especially facial and cardiac defects. The 1. Blank, M. C., Grinberg, I., Aryee, E., Laliberte, C., Chizhikov, V. V., degree of hydrocephalus is an important determinant in the degree Henkelman, R. M., & Millen, K. J. (2011). Multiple developmental of developmental problems in patients with DWM (11). programs are altered by loss of Zic1 and Zic4 to cause Dandy-Walker malformation cerebellar pathogenesis. Development, 138(6), 1207-1216. DWM may present as part of PHACES syndrome – posterior fossa 2. Coppieters, F., Lefever, S., Leroy, B. P., & De Baere, E. (2010). CEP290, abnormalities, hemangiomas of face and scalp, arterial a gene with many faces: mutation overview and presentation of Figure 3 MRI Sagittal View 1 abnormalities, cardiac defects, eye anomalies, and sternal CEP290base. Human mutation, 31(10), 1097-1108. abnormalities (12). Our patient did not undergo echocardiography 3. Cruz, A. J. M., & De Jesus, O. (2020). Encephalocele. StatPearls or eye exams to confirm the presence of any abnormalities. [Internet]. 4. Dastoli, P. A. D., Nicácio, J. M., da Costa, M. D. S., Suriano, I. C., da Genetic Associations Silva, M. C., & Cavalheiro, S. (2020). Hydrocephalus and Dandy-Walker Malformation: a review. Archives of Pediatric Neurosurgery, e442020- Certain syndromes, including Meckel-Gruber syndrome, have been e442020. associated with encephalocele and Dandy Walker malformation (3, 5. Ferri, L., Funghini, S., Fioravanti, A., Biondi, E. G., la Marca, G., Guerrini, R., ... & Morrone, A. (2014). Aminoacylase I deficiency due to 10, 14). Meckel-Gruber syndrome is an autosomal recessive ACY1 mRNA exon skipping. Clinical genetics, 86(4), 367-372. disorder characterized by neurological abnormalities, polydactyly, 6. Fetal growth assessment. (n.d.). Retrieved January 31, 2021, from polycystic dysplastic kidneys, and liver anomalies. It has been https://fetalmedicine.org/research/assess/growth linked to a paternally inherited homozygous nonsense mutation in 7. Markovic, I., Bosnjakovic, P., & Milenkovic, Z. (2020). Occipital the CEP290 gene (8). The UniProtKB gene database identifies Encephalocele: Cause, Incidence, Neuroimaging and Surgical CEP290 as involved in centrosome recruitment in ciliogenesis. Management. Current Pediatric Reviews, 16(3), 200-205. Numerous CEP290 mutations have been identified as associated 8. Molin, A., Benoist, G., Jeanne-Pasquier, C., Elkartoufi, N., Litzer, J., with , such as Meckel-Gruber syndrome (2). Further Decamp, M., ... & Leporrier, N. (2013). 12q21 Microdeletion in a studies indicate a heterozygous mutation in the CEP290 gene may with Meckel syndrome involving CEP290/MKS4. European journal of Figure 4 MRI Sagittal View 2 , 56(10), 580-583. have a role in some mechanisms related to development of 9. Mullegama, S. V., & Elsea, S. H. (2016). Clinical and molecular aspects ciliopathic conditions (13). Physical findings in our patient have of MBD5-associated neurodevelopmental disorder (MAND). European some overlap with physical findings associated with Meckel-Gruber Journal of Human Genetics, 24(9), 1235-1243. syndrome. Our patient also has a paternally-derived heterozygous 10. Rehman, L., Farooq, G., & Bukhari, I. (2018). Neurosurgical mutation in the CEP290 gene. interventions for occipital encephalocele. Asian Journal of Neurosurgery, 13(2), 233. Mutations in ACY1 are associated with Aminocyclase 1 Deficiency 11. Sharmin, L. (2018). Dandy-Walker Malformation—A Rare Cause of (ACY1D). This is an autosomal recessive inborn error of Congenital Hydrocephalus. Journal of Enam Medical College, 8(2), 114- metabolism, associated with neurological symptoms (5). Our 115. 12. Stambolliu, E., Ioakeim-Ioannidou, M., Kontokostas, K., Dakoutrou, M., patient has a heterozygous deletion inherited from the mother. & Kousoulis, A. A. (2017). The most common comorbidities in Dandy- Walker syndrome patients: a systematic review of case reports. Journal MBD5 gene mutations have been associated with MBD-5 of child , 32(10), 886-902. Associated Neurodevelopmental Disorder (MAND). This disorder is 13. Travaglini, L., Brancati, F., Attie‐Bitach, T., Audollent, S., Bertini, E., primarily characterized by a deletion that causes motor delay, Kaplan, J., ... & Valente, E. M. (2009). Expanding CEP290 mutational speech impairment, intellectual disability, seizures, and Autism spectrum in ciliopathies. American Journal of Medical Genetics Part Spectrum Disorder. Variants in the MBD5 gene, as seen in our A, 149(10), 2173-2180. patient, have been associated with a similar but milder phenotype 14. Yaqoubi, H. N. A., & Fatema, N. (2018). Meckel Gruber syndrome to the deletion syndrome of MAND (9). Our patient’s neurological associated with —an unusual reported case. Oxford Figure 5 MRI Transverse View exam did not show any abnormalities for gestational age. medical case reports, 2018(2), omx092. 15. Zamora, E. A., & Ahmad, T. (2019). Dandy Walker Malformation. StatPearls Publishing.