Fetal Pathology of Neural Tube Defects - An Overview of 68 Cases

Abstract

Introduction: The prevalence of neural tube defects worldwide is 1 - 2 per 1000 neonates. Neural tube defects result from a disturbance of neurulation in the 3rd or 4th week of development and thus represent the earliest manifestation of organ malformation. Neural tube defects (NTD) are classified into cranial dysraphism leading to anencephaly or meningoencephalocele and spinal dysraphism with or without meningomyelocele. In isolated form they have multifactorial causes, and the empirical risk of recurrence in Central Europe is 2%. As associated malformations they tend to occur sporadically, and in monogenic syndromes they follow Mendelian inheritance patterns with a high risk of recurrence.

Patients: Autopsies were performed on 68 fetuses following a prenatal diagnosis of NTD and induced abortion.

Results: The incidence of NTDs in our autopsied fetuses was 8% and 11% in fetuses with malformations. The percentage of fetuses with anencephaly, encephalocele or spina bifida was 24, 18, and 60%*, respectively. Analysis of the sex distribution showed a female preponderance in cranial dysraphisms but the sex distribution of spina bifida cases was equal. The extent and localization of NTDs varied, with lumbosacral cases clearly predominating. The proportion of isolated, associated and syndromic neural tube defects was 56, 23.5 and 20.6% respectively. In the majority of syndromes, the neural tube defect represented a not previously observed syndromic feature.

Conclusion: The high proportion of NTDs with monogenic background underlines the importance of a syndrome oriented fetal pathology. At the very least it requires a thourough photographic and radiographic documentation of the fetal phenotype to enable the genetic counsellor to identify a syndromic disorder. This is necessary to determine the risk of recurrence, arrange confirming mutation analyses and offer targeted prenatal diagnosis in subsequent pregnancies.

Keywords: Chiari II malformation; encephalocele; fetal pathology; neural tube defects; spina bifida.

Fig. 1

Anencephaly with meroacrania in a female fetus of 18 weeks of gestation ( a ); anencephaly with holoacrania involving the occipital foramen magnum in a male fetus of 17 + 2 weeks of gestation ( b ) compared with ultrasound image ( d ); typical appearance of anencephaly and proptosis caused by defects of the orbital roof, long nose and macrognathia in the fetus shown in Fig.  a ( c ); extensive craniorachischisis with involvement of the skull and the entire spine in a female fetus of 16 weeks of gestation ( e ).

Fig. 2

Double meningoencephalocele in a male fetus with Meckel-Gruber syndrome in the 19th week of gestation ( a ); small covered encephalocele at the occipitocervical junction in a female fetus with associated Dandy-Walker cyst in the 19th week of gestation ( b ); double meningoencephalocele with MKS – see Fig.  a – after exposure of the posterior skull ( c ); large occipital encephalocele on prenatal ultrasound (transverse plane) with prolapse of parts of the cerebrum and subsequent microcephaly in a female fetus with del(13q) syndrome at 21 + 5 weeks of gestation (Thomas v. Ostrowski, Praenatalmedizin Dorsten) ( d ).

Fig. 3

Double neural tube defect with small, partially skin-covered occipital meningoencephalocele (MEC) and thoracic meningomyelocele (MMC) in a female fetus in the 25th week of gestation ( a ); MEC on three-dimensional prenatal ultrasound ( b ↘) and MMC in the horizontal plane ( d  ↘↘); X-ray showing vertebral malformation at Th2 – Th5 in the region of the MMC ( c ).

Fig. 4

“In-plane” view of lumbosacral spina bifida (L2 – S1) in a female fetus at 19 + 2 weeks of gestation showing an oval soft tissue skin defect with strongly raised edges, a wide vertebral arch (Wb) fissure, exposed spinal canal with exposed non-closed neural plate ( a ) and cross-sectional view of the spina bifida ( c ). Cross-sectional histological image showing a flat neural plate with an open neural groove and open subarachnoid space (HE × 1.25) ( b ).

Fig. 5

Thoraco-lumbo-sacral spina bifida in a male fetus of 21 + 6 weeks of gestation. The fetus shows gibbus-like kyphosis (↘), wide median fissure at the spinal arches Th8 – S2, wedged vertebrae and hemivertebrae in the thoraco-lumbo-sacral region on lateral and posterior-anterior X-ray ( a and b ). Dorsal view of the open spinal canal with exposed necrotic neural tissue ( c ).

Fig. 6

Chiari II malformation (CM-II) in the female fetus (20th week of gestation) shown in Fig. 4 . The skull and spinal canal have been opened dorsally; there is herniation of parts of the cerebellum and medulla oblongata through the distended occipital foramen magnum (* edge) into the spinal canal ( a ). Brainstem and upper spinal cord show distinct elongation and Z-shaped kinking and lateral ventricles are dilated due to hydrocephalus as shown by a longitudinal section through the right cerebral hemisphere ( b ).

Abb. 1

Anenzephalie bei Meroakranie eines weiblichen Feten der 18. SSW ( a ); Anenzephalie bei Holoakranie unter Einbeziehung des Foramen occipitale magnum bei männlichem Fetus der 17 + 2 SSW ( b ) im Vergleich zur sonografischen Darstellung ( d ); typische Facies eines Anenzephalus mit Protrusio bulbi infolge Defekt des Orbitadachs, langer Nase und Makrognathie beim Fetus der Abb.  a ( c ); ausgedehnte Kraniorachischisis unter Einbeziehung des Schädels sowie der HWS, BWS und LWS eines weiblichen Fetus in der 16. SSW ( e ).

Abb. 2

Doppelte Meningoenzephalozele eines männlichen Fetus der 19. SSW mit Meckel-Gruber-Syndrom und MKS3 -Mutation ( a ); kleine gedeckte Enzephalozele am okzipitozervikalen Übergang bei einem weiblichen Fetus der 19. SSW mit assoziierter Dandy-Walker-Zyste ( b ); doppelte Meningoenzephalozele bei MKS – s. Abb.  a – nach Freilegung der hinteren Schädelkalotte ( c ); große okzipitale Enzephalozele im pränatalen Ultraschall (Transversalebene) mit Prolaps von Großhirnanteilen und konsekutiver Mikrozephalie bei einem weiblichen Fetus der 21 + 5 SSW mit del(13q)-Syndrom (Thomas v. Ostrowski, Praenatalmedizin Dorsten) ( d ).

Abb. 3

Zweifacher Neuralrohrdefekt mit kleiner partiell überhäuteter okzipitaler Meningoenzephalozele (MEC) und thorakaler Meningomyelozele (MMC) bei einem weiblichen Fetus der 25. SSW ( a ); MEC im 3-dimensionalen pränatalen Ultraschall ( b ↘) und MMC in der Horizontalebene ( d  ↘↘); röntgenologisch erkennbare Wirbelkörperfehlbildungen Th2 – Th5 im Bereich der MMC ( c ).

Abb. 4

Lumbosakrale Spina bifida (L2 – S1) bei weiblichem Fetus der 19 + 2 SSW mit ovalärem Haut-Weichteil-Defekt und wallartig aufgeworfener Hautbegrenzung, breiter Spaltung der Wirbelbögen (Wb) und freiliegendem Rückenmarkskanal mit exponierter Medulla spinalis in der Aufsicht ( a ) und am Spina-bifida-Querschnitt ( c ). Histologisch flache Neuralplatte mit offener Neuralrinne, damit offenem Liquorraum am Querschnitt (HE × 1,25) ( b ).

Abb. 5

Thorakolumbosakrale Spina bifida bei einem männlichen Fetus der 21 + 6 SSW mit gibbusförmiger Kyphose (↘), breiter Spaltung der Wirbelbögen Th8 – S2 und thorakolumbosakralen Keil- und Halbwirbeln im seitlichen und p.–a. Röntgenbild ( a und b ). Dorsalansicht des offenen Wirbelkanals mit exponiertem nekrotischen Neuralgewebe ( c ).

Abb. 6

Chiari-II-Malformation beim weiblichen Fetus der 20. SSW aus Abb. 4 . Schädel und Wirbelkanal dorsal eröffnet, Herniation von Anteilen des Cerebellums und der Medulla oblongata durch das erweiterte Foramen occipitale magnum (* Absetzungskante) in den Wirbelkanal ( a ) mit deutlicher Elongation und Z-förmiger Abknickung von Hirnstamm und oberem Zervikalmark sowie hydrozephal erweiterten Seitenventrikeln am Sagittalschnitt durch die rechte Großhirnhemisphäre ( b ).