Craniorachischisis and omphalocele in a stillborn cynomolgus monkey (Macaca fascicularis)

Abstract

Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities.

Fig. 1

Physical characteristics of infant with craniorachischisis and omphalocele. a. Face of the infant with no skull above wide-set, protruding eyes and flattened nose. Lips and tongue were normal, and palate was intact and well-formed. b. The back of the infant shows the considerably shortened trunk as compared with a term stillbirth. Normal measurements were found for the humeri, femora, and tail. Tight flexures are seen at the joints. c. Left hand of the infant with the fingers tightly folded over the palm, illustrating the tight flexures that were observed in all limbs. d. The back of the infant showing extent of craniorachischisis through the thoracic vertebrae. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 2

Whole-body radiograph. Note the dysplastic cervical vertebrae and hemivertebra at the T5–6 level.

Fig. 3

Whole body Maximum Intensity Projection (MIP)-images from a volumetric microCT scan. [A three-dimensional 360° movie of the microCT scan is available at www.interwcience.wiley.com. Three-D glasses are needed for viewing the movie.] a. Ventral MIP-view shows craniorachischisis with abnormal widening of the vertebral bodies, angulation of the lateral walls, and absence of the neural arches through the cervical and thoracic areas. Only 9 ribs were present instead of the 12 found in normal M. fascicularis. b. Lateral MIP-view demonstrates the lack of bony elements in the skull above the orbits and clearly shows the tight flexures in the elbows, wrists, hip, knees, ankles, and digits as well as bowing of the radii. The infant’s mandible was separated during the necropsy.