A detailed musculoskeletal study of a fetus with anencephaly and spina bifida (craniorachischisis), and comparison with other cases of human congenital malformations

Abstract

Few descriptions of the musculoskeletal system of humans with anencephaly or spina bifida exist in the literature. Even less is published about individuals in which both phenomena occur together, i.e. about craniorachischisis. Here we provide a detailed report on the musculoskeletal structures of a fetus with craniorachischisis, as well as comparisons with the few descriptions for anencephaly and with musculoskeletal anomalies found in other congenital malformations. We focused in particular on the comparison with trisomies 13, 18, and 21 because neural tube defects have been associated with such chromosomal defects. Our results showed that many of the defects found in the fetus with craniorachischisis are similar not only to anomalies previously described in the available works on musculoskeletal phenotypes seen in fetuses with anencephaly and spina bifida, but also to a wide range of other different conditions/syndromes including trisomies 13, 18 and 21, and cyclopia. The fact that similar anomalies are seen commonly not only in a wide range of different syndromes, but also as variants of the normal human population and as the 'normal' phenotype of other animals, supports Pere Alberch's unfortunately named idea of a 'logic of monsters'. That is, it supports the idea that development is so constrained that both in 'normal' and abnormal development one sees certain outcomes being produced again and again because ontogenetic constraints only allow a few possible outcomes, thus also leading to cases where the anatomical defects of some organisms are similar to the 'normal' phenotype of other organisms. In fact, this applies not only to specific anomalies but also to general patterns, such as the fact that in pathological conditions affecting different regions of the body, one consistently sees more defects on the upper limbs than on the lower limbs. Such general patterns are, again, seen in the fetus examined for this study, which had 29 muscle anomalies on the right upper limb and 22 muscle anomalies on the left upper limb, vs. seven muscle anomalies on the right lower limb and two on the left lower limb. It is therefore hoped that this work, which is part of our effort to describe and compile information on human musculoskeletal defects found in a wide range of conditions, will contribute not only to a better understanding of craniorachischisis in particular and of human congenital malformations in general, but also to broader discussions on the fields of comparative anatomy, and developmental and evolutionary biology.

First use of anatomical networks to study modularity and integration of heads, forelimbs and hindlimbs in abnormal anencephalic and cyclopic vs normal human development

“…As noted in our previous publications on the gross anatomy of the T18 fetus 17,26–28 and the anencephalic fetuses 18 included in the AnNA of the present work, the more marked differences between these fetuses and the ‘normal’ (see below) phenotype of a 7-month-old fetus are found in the head (Figs 1–4). This was to be expected as the abnormal fetuses have severe head malformations: anencephaly (Fig.…”

“…Of the two FLs of the anencephalic fetus 1 (Figs 8 and 9; Tables 15 and 16), the right is clearly the more abnormal in terms of its gross anatomy, lacking a radius and a digit 2 18 . Accordingly, in terms of its modules, the left FL displays a mix of modules that are often seen in either the prenatal or adult normal phenotype (e.g., “carpals/digit 5” and “digit 2”) and that are quite unique.…”

“…Interestingly, also on the left FL of the anencephalic fetus 1 there is a very peculiar module that includes only the occipital bone, vertebrae, and the rhomboid complex, which is the result of the presence of an extra, abnormal muscle in this complex connecting the vertebrae to the head: the rhomboideus occipitalis (see SI and Alghmadi et al . 18 ). This latter muscle is often seen in humans with severe birth defects (see, e.g., reviews by Smith et al .…”

“…9; for more details see SI and Alghamdi et al . 18 ). As also discussed in those previous studies, and in Diogo et al .…”

“…Anencephaly results from failure of the cranial portion of the neural tube to fuse, resulting in partial or complete absence of cranial vault (frontal, parietal, occipital, temporal, sphenoid, and ethmoid bones) with absence of overlying tissues and malformation and damage of fundamental brain structures (recently reviewed by Alghamdi et al . 18 ). The present study will therefore provide new data to discuss these and other broader developmental and evolutionary hypotheses and to better understand the links between normal and abnormal development, morphological diversity, variations and defects, and modularity and integration.…”