Classification, clinical features, and genetics of neural tube defects

Abstract

Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant death, or significant lifelong handicaps. The malformations result from failure of the neural folds to fuse in the midline, and form the neural tube between the third and the fourth week of embryonic development. This review article discusses their classification, clinical features, and genetics. Most NTDs are sporadic and both genetic, and non-genetic environmental factors are involved in its etiology. Consanguinity was suggested to contribute to the high incidence of NTDs in several countries, including Saudi Arabia. Syndromes, often associated with chromosomal anomalies, account for <10% of all NTDs; but a higher proportion (20%) has been documented in Saudi Arabia. Genetic predisposition constitutes the major underlying risk factor, with a strong implication of genes that regulate folate one-carbon metabolism and planar cell polarity.

Figure 1

Images showing cranial neural tube defects: A) a newborn with anencephaly. B, C & D) Anterior encephalocele. Sequential coronal MRI scan showing brain herniation through the right nasal bone (arrows in C & D); and E) large posterior encephalocele.

Figure 2

Images showing: A) posterior encephalocele (arrow) seen in an x-ray carried out on a newborn who had Meckel-Gruber syndrome. The abdomen is distended due to associated polycystic kidneys. Polydactyly of the right foot is also shown; B, C, & D) MRI features of a child who had Joubert syndrome associated with posterior encephalocele. Note the osseous defect of the cranium (arrow, B); C) axial image at the level of midbrain shows the classic “molar tooth sign” with the roots of the tooth formed by the thick and horizontally oriented superior cerebellar peduncles (arrows); D) parasagittal image demonstrating a thick and horizontally oriented superior cerebellar peduncle (arrow); E & F) holoprosencephaly; E) sagittal MRI image showing an associated encephalocele (arrow); and F) coronal image revealed fusion of the cerebral hemispheres, associated with band heterotopias (arrows).

Figure 3

Classification of spinal dysraphisms.

Figure 4

Images showing: A) newborn with thoracic myelomeningocele. The diaphanous sac is filled with CSF and contains fragile vessels in its membrane. A placode-containing remnants of the nervous system can be seen in the lower half of the lesion; B) a one-day-old neonate with myelomeningocele at the lumbar region. A T2-weighted MRI image with fat saturation showing low-lying spinal cord tethered to the upper end of spina bifida (arrow); C) sagittal brain MRI image shows features of Chiari II malformation. There is small-sized posterior fossa, downward herniation of the cerebellar tonsils, through the foramen magnum (4), deformed shape of the fourth ventricle (3), tectal beaking (2); and prominent massa intermedia (1).

Figure 5

An image showing lipomyelomeningocele:A) a newborn with subcutaneous mass above the gluteal crease; B) sagittal T1-weighted MRI image (taken at the age of 26 months) shows large subcutaneous lipoma with fatty tissue extending through a wide posterior spina bifida into the spinal canal (arrow) to connect with the placode (P); C) sagittal T2-weighted MRI image (with fat saturation) showing the lipoma attached (arrow) to the placode (P). Note the distended urinary bladder (asterix) with irregularity of the posterior wall suggesting the presence of neurogenic bladder.

Figure 6

Images showing: A & B) thoracic and cervicocephalic intramedullary lipoma: A) the affected 9-month-old presented as floppy infant syndrome. Spinal CT scans showed an expanded cervicothoracic spinal cord filled by a large low-density mass (image not shown); B) cranial CT revealed extension of the low-density mass (lipoma) in the posterior fossa (arrow); C & D) Caudal agenesis. C) sagittal T1-weighted (T1W) MRI image showing the less severe form, with blunted appearance of the distal cord (arrow) and dysplastic sacrum; and D) sagittal T1W MRI revealing severe caudal agenesis. There is also blunted appearance of the distal spinal cord (arrow).

Figure 7

Images showing: A) a 9-year-old girl presenting with a remarkable hair tuft at the back above the gluteal fold; B) the left foot was smaller, had equinus posture, and showed spontaneously upgoing big toe; C) sagittal T2-weighted MRI showed features of diastematomyelia with thinning of the spinal cord (large arrow) resulting from the intervening subarachnoid space between the 2 hemicords. There is also remarkable widening of the spinal canal with tethering of the cord (small arrow). D-F) serial axial T-2 weighted images revealed that the spinal cord started to divide at the level of L2 (E) into 2 halves (F).