Abnormal Development of Human Musculature: Linking Development, Anatomical Variations and Defects, Atavisms, Order and Chaos and Medicine

Abstract

Most studies of birth defects in humans tend to focus on external features or hard tissues. Therefore, there are few descriptions of the anomalies of the musculoskeletal system and particularly there is a lack of detailed comparisons of anomalies between individuals with different syndromes and with other species. Such comparisons are key to shed light on both normal and abnormal developmental mechanisms and disturbances, and on development and evolution of our own species. For this study, a 28‐week‐old Trisomy 18 (T18) fetus and a 35‐week‐old Anencephaly fetus were dissected using standard micro‐ and macro‐dissection tools and a hand‐held camera, as well as a dissection microscope with an attached camera, and CT scans were performed for the analysis of skeletal structures. These data were combined with an extensive literature review of the ontogeny and development of the muscular system in normal and abnormal individuals. Regarding our own dissections of the T18 and anencephalic fetuses, we observed several anomalies. For example, in the right forearm of the T‐18 fetus, the 3rd layer of the forearm flexors had two muscle belies: the medial (flexor pollicis longus) sent two tendons to digits 1 & 2 and the lateral (flexor digitorum profundus) sent three tendons to digits 3, 4 & 5. The spatial relation of those muscle bellies provides information that helps us to understand the links between normal and abnormal development and evolution because this is a case of atavism: the flexor pollicis longus was acquired during human evolution through a separation from the flexor digitorum profundus. Langer's axillary arch (a supernumerary muscle extends from latissimus dorsi to pectoralis major) was observed unilaterally in the T‐18 fetus. However, this muscle was also observed by us as a variation in two ‘normal’ fetuses (15 & 28 weeks of gestation) and described as a variation in a few ‘normal’ adults, showing the complex thin line between variations in the ‘normal’ population and anomalies in karyotypically ‘abnormal’ individuals. In fact, this link between variations and birth defects is also evidenced by the fact that, in general, the number of muscle anomalies in the lower limbs was lower than that in the upper limbs, a pattern that is also seen in variations of the normal population. Importantly, our dissections and comparisons revealed that certain anatomical patterns are often found in conditions that have very different genetic and pathological backgrounds, supporting the ill‐named “logic of monsters” hypothesis of Pere Alberch, according to which even in the extreme cases of birth defects there is still a discernable, marked “order”, instead of random, chaotic phenotypes. This is related to strong internal constraints limiting the amount of possible developmental outcomes, that is the same phenotype is produced over and over despite the fact that the specific causes leading to the anomalies are different. Such “order” is only disturbed in very rare and extreme anomalies, including cases of marked asymmetry, such as those mentioned above, which indicate a relaxation of local homeostasis but, importantly, do not result in a global lack of homeostasis that would lead to completely random phenotypes. These important links between development, anatomical variations and defects, and order and chaos are crucial for medicine because they add a very important element in the detection and potential resolution (e.g. through surgeries) of congenital malformations: the element of predictability.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.