On the origin of congenital limb deficiency

Newswise — A revolutionary new approach to the topic of congenital birth defects has been published in the pages of the American Journal of Medical Genetics as a cover story this week (Vol. 19, Issue 6, June 2023).

David R. Hootnick, M.D., of the Departments of Orthopedic Surgery, Pediatrics and Cell and Developmental Biology at SUNY Upstate Medical University, has revealed extensive clinical evidence that most human congenital long bone deficiencies of the lower limbs are the result of downstream effects of embryonic arterial dysgenesis, similar to that of thalidomide embryopathy; such limb deficiencies are, in fact, indistinguishable from those seen in the notorious thalidomide epidemic of the 1950s and 1960s.

According to Hootnick, over the past century, researchers have been led astray because of an almost exclusive reliance on X-ray analysis of such malformed limbs, while anatomy of the soft tissues, including the arteries, has been neglected. Also, despite the completion of the Genome Project over 20 years ago, few causes of congenital limb deficiencies have been identified.

Hootnick says that neat empirical terminologies for limb deficiencies have further muddied the waters of understanding by having established inaccurate straight line geometric terminologies, such as ‘absent’ fibula and ‘fibular hemimelia’ which dominate the birth coding systems and granting domains of various authorities. Lewis Holmes, M.D., of the Mass General Hospital for Children further asserted that this work provides unequivocal evidence that previous assumptions regarding “absent” fibula have been inaccurate.

According to Hootnick, recent publications reveal that the most commonly encountered long bone deficiency, ‘absent’ fibula, is a radiologic misnomer. An accurate appraisal of congenital deficiencies, one based on the pathologic anatomy of such affected limbs, demands revision of the currently employed terminologies.

He and his colleagues have suggested naming this group of conditions as the syndrome of “proximal femoral, fibular and midline metatarsals”as a starting point in recognition of the fact that the deficient skeletal structures faithfully follow the ingrowth pattern of new blood vessels in the sixth- and seventh-week embryonic limb, as illustrated in Gray’s Anatomy textbook.

Hootnick observed that this paradigm shift in understanding congenital limb deficiencies—that the missing blood vessels precede the visibly missing bones—explains why the multiple techniques for lengthening congenitally shortened bone mechanically over the past century by Codivilla in Spain, Wagner in Germany and most recently Ilizarov in Russia have always been fraught with difficulty because the shortened bones are biologically diminished due to reduced blood supply.