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Case Report
Bilateral cervical ribs in a Dobermann Pinscher M. Ricciardi; A. De Simone; F. Gernone; P. Giannuzzi “Pingry” Veterinary Hospital, Bari, Italy
Keywords Cervical ribs, computed tomography, dog
Summary An 11-year-old intact female Doberman Pinscher was presented with the complaint of non-ambulatory tetraparesis. Clinical and neurological examination revealed a caudal cervical spinal cord disfunction (C6-T2 spinal cord segments). Magnetic resonance imaging and computed tomographic (CT) findings of the cervical spine were consistent with caudal cervical spondylomyelopathy (CSM). During the diagnostic work-up for the cervical spine, bilateral bone anomalies involving the seventh cervical vertebra and the first ribs were found on radiographs and CT examination. The rib anomalies found in this Correspondence to Dr. M. Ricciardi Pingry Veterinary Hospital via Medaglie d'Oro 5 Bari 70126 Italy Phone: +39 080 553 3884 E-mail: [email protected]
dog appear similar to cervical ribs widely described in human medicine. In people, cervical ribs are associated with a high rate of stillbirth, early childhood cancer, and can cause the thoracic outlet syndrome, characterized by neurovascular compression at level of superior aperture of the chest. In dogs, only some sporadic anatomopathological descriptions of cervical ribs exist. In this report the radiographic and CT findings of these particular vertebral and rib anomalies along with their relationships with adjacent vasculature and musculature are shown intravitam in a dog. Specific radiographic and CT findings described in this report may help in reaching a presumptive diagnosis of this anomaly. Finally, their clinical and evolutionary significance are discussed. Vet Comp Orthop Traumatol 2015; 28: 145–150 http://dx.doi.org/10.3415/VCOT-14-07-0109 Received: July 23, 2014 Accepted: December 12, 2014 Epub ahead of print: February 4, 2015
Introduction A cervical rib is defined as a supernumerary rib, springing from one or both sides of one cervical vertebra usually the seventh, rarely the sixth, and very rarely the fifth (1). In the human population cervical ribs represent a rare, atavistic anomaly with an incidence of 0.2% to 1.0% (2, 3). They are twice as common in women as in men (68% versus 32%, respectively) and are bilateral in more than 50% of cases (4). To date descriptions of cervical ribs in dogs are limited to twelve reported necropsy findings, in which one or both transverse process of C7 resembled a rib.
Unfortunately, only a partial lateral radiograph and a single isolated vertebra in these anatomopathological specimens, are available for review (5, 6). In this report, we describe the presence of an anatomical anomaly involving the first ribs and the seventh cervical vertebra in a dog. The bone anomalies, resembling supernumerary cervical ribs, were found as incidental findings during the diagnostic work-up for a cervical spondylomyelopathy. The morphology of these bones and their relationships with the cervical spine and the adjacent musculature and vessels were assessed through the three-dimensional multislice computed tomography (CT).
Case description An 11-year-old, female Doberman Pinscher dog was evaluated for the complaint of a one month history of progressive inability to walk. Clinical and neurological examination findings included non-ambulatory tetraparesis, decreased postural reaction on all four limbs, severely decreased forelimb spinal reflexes, normal hindlimb spinal reflexes, and cervical discomfort. Neuroanatomic localization was the cervico-thoracic spinal cord (C6-T2 spinal cord segment – C4-T2 vertebral bodies). Haematology, serum chemistry analyses and urinalysis results were within normal limits. Orthogonal radiographic views of the cervico-thoracic and thoracic spine were obtained while the dog was under general anaesthesia. The lateral view radiographs demonstrated an abnormal triangular shape of the body of the C5-C6 vertebrae, narrowing of the C6-C7, and C7-T1 intervertebral disc spaces, and abnormal shape of the first ribs. The body of these bones appeared caudo-cranially flared and connected by a linear mineral opacity to the ventro-cranial aspect of the body of the seventh vertebra (C7) (▶ Figure 1 A). On ventrodorsal radiographic views, two welldefined rib-like opacities were visualized and were connected on both sides of the first ribs to the cranio-lateral aspect of C7. The left one showed a linear radiolucent area that separated it in two segments: one which was more cranial and connected to C7 (with perpendicular orientation to the axis of the spine), and a second directly connected to the body of the first rib (with parallel orientation to the axis of the spine) (▶ Figure 1 B). No anomalies in the shape and number of the remaining ribs were observed. Based on these findings, a presumptive diagnosis of cervical spondylomyelopathy with associated unknown
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Figure 1 A) Lateral and B) ventrodorsal radiographs of the cervico-thoracic spine. A) On the lateral view, the first ribs appear caudo-cranially flared and connected by a linear mineral opacity (arrow) to the ventro-cranial aspect of the body of the seventh vertebra. B) There are two well-defined rib-like opacities connecting on both sides the first ribs with the cranio-lateral aspect of the seventh vertebra (arrows). A radiolucent linear defect separates the left supernumerary rib in two segments (arrowhead). C5 = fifth cervical vertebra; C6 = sixth cervical vertebra.
Figure 2 Magnetic resonance imaging of the cervico-thoracic spine. A) Sagittal T2-weighted image; B) dorsal STIR; transverse T2-weighted image at C) C5-C6, D) C6-C7 and E) C7-T1 intervertebral disc spaces. There was severe C5-C6 and mild C6-C7 intervertebral disc protrusions with ventral spinal cord compression, dorsal C5-C6 spinal cord compression subsequent to hypertrophy of the ligamentum flavum and triangular shape of the C6 and C7 vertebral bodies. No signal changes of the cervicothoracic nerve roots were observed (C, D, E and arrows in B).
anomaly of the first ribs was made. In order to evaluate the spinal cord damage subsequent to the suspected cervical spondylomyelopathy and to clarify the anatomical relationships between the first ribs and the seventh vertebra, MRI and CT of the cervico-thoracic spine were performed after the radiographic examination. Magnetic resonance imaging was acquired under general anaesthesia using a 0.25 Tesla permanent magneta. The MRI sequences protocol included a fast spin echo T2-weighted acquired in sagittal and transverse planes, a short-tau inversion recovery (STIR) acquired in dorsal plane, and a spin echo T1-weighted acquired in sagittal and transverse planes before and after intravenous administration of paramagnetic contrast mediumb. Magnetic resonance imaging showed severe C5-C6 and mild C6-C7 intervertebral disc protrusions with ventral spinal cord compression, dorsal C5-C6 spinal cord compression subsequent to hypertrophy of the ligamentum flavum, and a triangular shape of the C6 and C7 vertebral bodies in the midsagittal plane. No signal changes of the cervico-thoracic nerve roots were observed (▶ Figure 2). Computed tomographic images were acquired using a 4-slice multi-detector CT scannerc, before and after the intravenous injection of iodinate contrast mediumd, with the patient positioned in sternal recumbency on the CT table under general anaesthesia. Computed tomography technical parameters were as follows: bone acquisition algorithm, 120 kVp, 200 mAs, 3.2 mm slice thickness, pitch of 0.8, and 0.75 s/rotation. Three-dimensional (3D) multiplanar reformatted and volume-rendered images were obtained using a dedicated 3D workstatione. Computed tomography images showed a flattened and highly flared profile of the first ribs. The proximal part of the ribs appeared Y-shaped, carrying a ESAOTE VET-MR GRANDE: Esaote, Genoa, Italy b Magnegita® – gadopentate dimeglumine 500 mmol/ ml – insight agents®; 0.15 mmol/kg BW: Agfa Healthcare Imaging Agents GmbH, Köln, Germany c Philips MX-8000: Philips Medical Systems, Cleveland OH, USA d Iopamigita®: Insight Agents GmbH®, Heidelberg, Germany e OsiriX DICOM-viewer: Pixmeo, Geneva, Switzerland
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M. Ricciardi et al.: Cervical ribs in a dog
short bone prominences that branched from the cranial margin of the rib and articulated with the transverse processes of C7. On the left side, the bone prominence articulated with C7 and was separated from the body of the first rib by an irregular line isoattenuating to soft tissue. A round region of interest (ROI) was traced within this gap to measure the Hounsfield Units (HU) mean attenuation value. A mean attenuation value of 87 HU was detected. No vascular anomalies nor abnormal anatomical relationships between the scalenus muscles, supernumerary ribs, and subclavian arteries and veins were observed. On the right side, the insertion of scalenus muscle was on the supernumerary rib (▶ Figure 3, ▶ Figure 4, ▶ Figure 5). Surgical decompression of the cervical spinal cord was performed by ventral slot at the C5-C6 intervertebral disc space followed by C5-C6 vertebral stabilization. After 15 days, the dog was re-evaluated and no significant improvement was noted. Based on its poor clinical condition the patient was euthanatized upon owner’s request. No further investigations were authorized by the owner.
Discussion The embryologic formation of cervical ribs seems to result from some failure in the conflict between forming brachial plexus and ribs. In higher vertebrates, the forming spinal nerves grow outwards at approximately right angles to the vertebral column to gain access to the developing limb buds and, as the column grows in length and the limbs descend, the nerves are forced to adopt an oblique course to reach the developing limbs. It is here that a conflict is said to arise between the passage of the nerves and the developing ribs. It is reported that when large nerve trunks press on comparatively small developing ribs, their growth is impeded and they remain stunted, forcing them ultimately to merge with the transverse process of the adjacent vertebra (7). In the thorax, where there is no conflict with a developing plexus, the ribs are free to grow in size and achieve independence from the column (1, 7–10). Animals that do not possess limbs, such as
Figure 3 Oblique multiplanar computed tomography reformatted images of the (A) left and (C) right first ribs. There is a flattened and highly flared profile of the first ribs (arrowheads). The proximal part appears Y-shaped, carrying short bone prominences (arrows) branching from the cranial margin of the rib and articulating with the transverse processes (tp) of C7. In the left rib, a non-calcified gap with cartilagineous mean attenuation values (rounded ROI–92 HU), resembling a pseudoarticulation, separates the cervical rib from the body of the first rib. B, D) Three-dimensional (3D) volume-rendered CT images of the cervico-thoracic spine (from C3 to T2), with complete removal of the scapulae. A 250 HU density threshold was used for the 3D display. Images illustrate (B) left lateral and (D) right lateral views. r2 = second rib.
snakes, retain paired ribs associated with virtually every vertebra with corresponding separate segmental nerves (8). The extent of growth of a cervical rib is determined by the nature of the obstruction on its path, which most frequently is nervous in origin (1, 7). However, this theory does not completely explain the embryologic formation of cervical ribs because it would be expected that the ribs should be associated with the upper cervical vertebrae (where there are no requirements for limb related nerves). To date, no reports exist describing a cervical rib associated with the upper four cervical vertebrae (7). In human medicine, there are four types of cervical ribs: 1) large, hypertrophic transverse process of C7; 2) rudimentary rib, but with free extremity and no connection to the first rib; 3) incomplete rib connected to the first thoracic rib by a fibrous band; 4) complete cervical rib fusing with
the first rib or connecting with it by a cartilaginous pseudoarticulation (11). In our patient, both the cervical ribs were attributable to the fourth type. The left cervical rib joined the first rib by a non-calcified gap that was suggestive of cartilaginous tissue based on its HU value. This arrangement appeared as a cartilaginous pseudoarticulation. The right cervical rib was completely fused with the first rib. The majority of people with cervical ribs are asymptomatic, but the presence of cervical ribs assumes clinical relevance in those people when these supernumerary bones compress one or more of the neurovascular structures traversing the superior aperture of the chest between the first rib and the scalenus muscles (costo-scalene triangle) (2). This condition is known as thoracic outlet syndrome (12, 13). Thoracic outlet syndrome is more commonly observed in women, and the onset of symp-
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A
B
C
D
Figure 4 Schematic representation of the costo-scalene triangle (asterisk) in normal (A) and cervical rib (B) patients as reported in human medical literature (14). When present, the supernumerary rib (cr) can narrow the costo-scalene triangle and compress the neurovascular bundle that passes between the middle and ventral (anterior) scalenus muscles. Schematic representation of the anatomical relationships between the neurovascular bundle, the first rib, and the scalenus muscles in a normal dog (C) and in our patient with the cervical rib (D). There is not a space comparable to the costo-scalene triangle between the middle and ventral scalene muscles and the neurovascular bundle passes ventrally to the ventral scalene muscle (15–18). In our dog, on the right side, the scalenus muscle was inserted directly on the cervical rib and, on both sides, there is no evidence of neurovascular compression. R1 = first rib; sm = middle scalene muscle; sv = ventral scalene muscle; a = subclavian artery; v = subclavian vein; p = brachial plexus; cr = cervical rib. Scheme A and B adapted from Brewin J, Hill M, Ellis H. The prevalence of cervical ribs in a London population. Clin Anat 2009; 22: 331–336. Scheme C and D original drawing.
toms usually occurs between 20 and 50 years of age (14). Approximately 10% of people with cervical ribs develop symptoms of thoracic outlet syndrome, secondary to the compression of the brachial plexus, also called neurogenic thoracic outlet syndrome (more than 90% of the cases), or due to compression of the subclavian vessels (either artery or vein), also called vascular thoracic outlet syndrome (less than 5% of cases). In some cases the neurological and vascular components may coexist (13–15).
The symptoms of nerve compression most frequently observed in neurogenic thoracic outlet syndrome are pain, paraesthesia, and weakness (12). Furthermore, compression of sympathetic neurons can cause vasomotor disturbances (16). In vascular thoracic outlet syndrome, compression of the subclavian artery can cause intermittent limb ischaemia, poststenotic dilatation of the artery or aneurysm formation. If the subclavian vein is compressed, venous insufficiency or even sub-
clavian vein thrombosis are observed (15, 16). In our patient, we were unable to investigate signs of possible brachial plexus compression secondary to the presence of the cervical ribs because of the concomitant non-ambulatory tetraparesis induced by the cervical spondylomyelopathy. However, no signal nor volume changes of brachial plexus nerve roots were evident on MRI. Furthermore, no clinical signs related to vascular compromise (neither arterial or venous) were observed on the forelimbs. Computed tomography angiography did not show compression of the subclavian arteries and veins. In humans, the scalenus muscles play an important role in the neurovascular compression when a supernumerary rib is present. Since the brachial plexus and the subclavian artery pass over the first rib just between the ventral (anterior) and middle components of the scalenus muscles (costo-scalene triangle), the neurovascular bundle can be compressed or trapped if this triangular space is narrowed by the presence of a cervical rib (4, 12–15). In domestic mammals, the subclavian artery and vein, and the brachial plexus pass ventrally to the ventral scalenus muscle, which is not separated from the middle component so as to create a space comparable to the costo-scalene triangle (15, 17–20) (▶ Figure 4). In our patient, CT did not show close anatomical relationships between scalene muscles, cervical ribs and subclavian arteries and veins. These vessels run on both sides much more ventrally to the muscles and to the supernumerary ribs (▶ Figure 5). Thus, this possible difference between humans and dogs in the level to which the subclavian vessels emerge from the chest and cross the scalene muscles, may influence differently the development of clinical signs in these two species, where cervical ribs are present. However the evaluation of further cases of cervical ribs in dogs is needed in order to verify this hypothesis. Cervical ribs may also have evolutionary significance in mammals. Among vertebrates, mammals have the lowest variability in the number and pattern of cervical vertebrae in comparison with other classes such as birds and reptiles (cervical ribs are normal in crocodiles) (1, 7). The only ex-
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M. Ricciardi et al.: Cervical ribs in a dog
ception is found in cervical rib cases in which the supernumerary ribs represent a partial or whole transformation of the seventh cervical vertebra into the first thoracic vertebra, thus, reducing the number of cervical vertebrae. In all vertebrate classes, the patterning of the axial skeleton is regulated by Hox genes and development of cervical ribs is a process that seems to be particularly susceptible to perturbations in Hox gene expression (21, 22). Interestingly, the most common abnormalities found in Hox gene-mutant mice are cervical ribs (23). At the same time, Hox genes have been shown to be involved in the proliferation of cell lines in mice and humans (24–26). Changes in Hox gene expression have been demonstrated for several types of tumours, including some childhood cancers, such as neuroblastoma, nephroblastoma and leukaemia, that were found to be associated with a high incidence of vertebral anomalies (24–27). A high incidence of cervical ribs was found in another study specifically devoted to find vertebral anomalies in 750 children with embryonal cancers (28). An incidence of around 25% of cervical ribs was found for the following embryonal and childhood cancers: neuroblastoma, brain tumour (astrocytoma and medulloblastoma), acute lymphoblastic and myeloid leukaemia, soft tissue sarcoma, nephroblastoma and endothelial myeloma (28). Furthermore, a strong association between cervical ribs and stillbirth has been described both in mice and humans (29–34). One study showed that at least 78% of the human foetuses with a cervical rib die before birth (35). Moreover data from autopsies performed on 225 stillborns (≥20 weeks) and 93 deceased live-born infants showed an overall higher prevalence of cervical ribs in stillborns than in liveborns who died in the first year (43.1% versus 11.8%) (34). Cervical ribs are due to disturbance of embryogenesis of the cervical axial skeleton, which in turns seems to be linked, as negative pleiotropic effect, to neoplastic proliferation of cell lines and a high rate of stillbirth and embryonal/childhood cancer. Consequently, these bone anomalies, for which inheritance has been suggested in dogs, are rare because most individuals
Figure 5 A) Transverse multiplanar computed tomography reformatted images at the level of the seventh cervical vertebra (C7). B) Oblique multiplanar computed tomography reformatted images of the right first rib at the level of the scalene muscles (sc). On both sides, the subclavian arteries and veins run ventrally to the cervical ribs (arrows) without anatomical relationships with the scalene muscles. On the right side, the insertion of scalene muscles was on the subernumerary rib (arrow in B). Rsa = right subclavian artery; lsa = left subclavian artery; rsv = right subclavian vein; lsv = left subclavian vein; R1 = first right rib; R2 = second right rib. The right subclavian vein is still not filled with contrast medium.
possessing them die before reaching a reproductive age (developmental constraint) (6, 23, 34). Based on these data it is possible to speculate that the incidence of cervical rib cases in dogs may be heavily underestimated due to a possible high rate of stillbirth.
Conclusion In conclusion, this report describes the radiographic and CT imaging findings of bilateral cervical ribs in a dog. The anatomy of these particular vertebral and rib anomalies along with their relationships with adjacent vasculature and musculature were especially well delineated on multiplanar and 3D volume-rendered CT imaging. In this case, the supernumerary bones were found as incidental findings; no vascular disturbances were evident and brachial plexus evaluation was not completely reliable clinically. However, further cases of cervical ribs in dogs need to be evaluated in order to establish the anatomical relationships between these supernumerary bones, the scalenus muscles, the first ribs, and their implication in neurovascular compression. In the absence of advanced knowledge on their clinical significance, the authors’ opinion is that the occurrence of cer-
vical ribs should be considered in the list of differential diagnosis in dogs presenting signs of nerve root or vascular compression affecting the forelimbs. Conflict of interest
None declared.
References 1. Adson AW, Coffey JR. Cervical rib; a method of anterior approach for relief of symptoms by division of the scalenus anticus. Ann Surg 1927; 85: 839–857. 2. Zou Chang K, Likes K, Davis K, et al. The significance of cervical ribs in thoracic outlet syndrome. J Vasc Surg 2013; 57: 771–775. 3. Gladstone RJ, Wakele CPG. Cervical ribs and rudimentary first thoracic ribs considered from the clinical and etiological standpoint. J Anat 1932; 66: 334–370. 4. Sanders RJ, Hammond SL. Management of cervical ribs and anomalous first ribs causing neurogenic thoracic outlet syndrome. J Vasc Surg 2002; 36: 51–56. 5. Morgan JP. Congenital anomalies of the vertebral column of the dog: A study of the incidence and significance based on a radiographic and morphologic study. Vet Radiol Ultrasound 1968; 9: 21–29. 6. Breit S, Kunzel W. Osteologische Besonderheiten an Wirbelsaulen von Rassehunden: eine röntgenologische und morphologische Studie [Osteological peculiarities of the vertebrae from pedigree dogs: a radiological and morphological study]. Wiener Tierarztliche Monatsschrift 1998; 85: 340–350.
© Schattauer 2015
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M. Ricciardi et al.: Cervical ribs in a dog 7. Black S, Scheuer L. The ontogenetic development of the cervical rib. Int J Osteoarchaeol 1997; 7: 2–10. 8. Davis DB, King JC. Cervical rib in early life. Am J Dis Child 1938; 56: 744–755. 9. Larsen WJ. Human Embryology. Edinburgh: Churchill Livingstone 2001; 84–104. 10. White JC, Poppel MH, Adams R. Congenital malformations of the first rib. Surg Gynaecol Obstet 1945; 81: 643–659. 11. Gruber W. Ueber die Halsrippen des Menschen mit vergleichend-anatomischen Bemerkungen [About the cervical ribs of man with comparative observations]. St. Petersburg: Commissionnaires de l'Académie Impériale des Sciences; 1869. pg. 614. 12. Urschel HC, Razzuk MA. Neurovascular compression in the thoracic outlet: changing management over 50 years. Ann Surg 1998; 228: 609–617. 13. Arthur LG, Teich S, Hogan M, et al. Pediatric thoracic outlet syndrome: a disorder with serious vascular complications. J Pediatr Surg 2008; 43: 1089–1094. 14. Köknel Talu G. Thoracic outlet syndrome. Agri 2005; 17: 5–9. 15. Brewin J, Hill M, Ellis H. The prevalence of cervical ribs in a London population. Clin Anat 2009; 22: 331–336. 16. Atasoy E. Thoracic outlet compression syndrome. Orthop Clin North Am 1996; 27: 265–303 17. Evans E, de Lahunta A. Miller's Anatomy of the Dog. 4th ed. Philadelphia, PA: Elsevier; 2013. pg. 213, 459-461, 507, 544, 620. 18. Barone R. Anatomia comparata dei mammiferi domestici. Vol. 2: Parte seconda – Miologia [Comparative anatomy of domestic mammals. Vol. 2:
19.
20.
21. 22.
23.
24.
25.
26.
Part II - Myology]. 3rd ed. Bologna: Edagricole, 2003. pg. 541, 551. Barone R. Anatomia comparata dei mammiferi domestici. Vol. 5: Angiologia. Parte prima: cuore e arterie [Comparative anatomy of domestic mammals. Vol. 5: Angiology. Part I: Heart and arteries]. 3rd ed. Bologna: Edagricole, 2003. pg. 217. Barone R. Anatomia comparata dei mammiferi domestici. Vol. 5: Angiologia. Parte seconda: vene e sistema linfatico [Comparative anatomy of domestic mammals. Vol. 5: Angiology. Part II: Veins and lymphatic system]. 3rd ed. Bologna: Edagricole, 2003. pg. 153-158. Krumlauf R. Hox genes in vertebrate development. Cell 1994; 78: 191–201. Horan GSB, Nagy Kovacs E, Behringer RR, et al. Mutations in paralogous Hox genes result in overlapping homeotic transformations of the axial skeleton: evidence for unique and redundant function. Dev Biol 1995; 169: 359–372. Galis F. Why do almost all mammals have seven cervical vertebrae? Developmental constraints, Hox genes, and cancer. J Exp Zool 1999; 285: 19–26. Corte G, Airoldi I, Briata P, et al. The homeotic gene products in the control of cell differentiation and proliferation. Cancer Detect Prev 1993; 17: 261–266. Lawrence HJ, Sauvageau G, Humphries RK, et al.The role of Hox homeobox genes in normal and leukemic hematopoiesis. Stem Cells 1996; 14: 281–291. Anbazhagan R, Raman V. Homeobox genes: molecular link between congenital anomalies and cancer. Eur J Cancer 1997; 33: 635–637.
27. Manohar CF, Salwen HR, Furtado MR, et al. Upregulation of Hoxc6, Hoxd1, and Hoxd8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation. Tumor Biol 1996; 14: 34–47. 28. Schumacher R, Mai A, Gutjahr P. Association of rib anomalies and malignancy in childhood. Eur J Pediatr 1992; 151: 432–434. 29. Jeannotte L, Lemieux M, Charron J, et al. Specification of the axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes Dev 1993; 7: 2085–2096. 30. Peters H. Varietäten der Wirbelsäule menschlicher Embryonen [Varieties of the spine of human embryos]. Gegenbaurs Morph Jahrbuch 1927; 58: 440–477. 31. Noback CR, Robertson GG. Sequences of appearance of ossification centers in the human skeleton during the first five prenatal months. Am J Anat 1951; 89: 1–28. 32. Meyer DB. The appearance of cervical ribs during early human fetal development. Anat Rec 1978; 190–481. 33. Bots J, Wijnaendts LC, Delen S, et al. Analysis of cervical ribs in a series of human fetuses. J Anat 2011; 219: 403–409. 34. Furtado LV, Thaker HM, Erickson LK, et al. Cervical ribs are more prevalent in stillborn fetuses than in live-born infants and are strongly associated with fetal aneuploidy. Pediatr Dev Pathol 2011; 14: 431–437. 35. Galis F, Van Dooren TJM, Feuth JD, et al. Extreme selection in humans against homeotic transformations of cervical vertebrae. Evolution 2006; 60: 2643–2654.
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Case Report
Bilateral cervical ribs in a Dobermann Pinscher M. Ricciardi; A. De Simone; F. Gernone; P. Giannuzzi “Pingry” Veterinary Hospital, Bari, Italy
Keywords Cervical ribs, computed tomography, dog
Summary An 11-year-old intact female Doberman Pinscher was presented with the complaint of non-ambulatory tetraparesis. Clinical and neurological examination revealed a caudal cervical spinal cord disfunction (C6-T2 spinal cord segments). Magnetic resonance imaging and computed tomographic (CT) findings of the cervical spine were consistent with caudal cervical spondylomyelopathy (CSM). During the diagnostic work-up for the cervical spine, bilateral bone anomalies involving the seventh cervical vertebra and the first ribs were found on radiographs and CT examination. The rib anomalies found in this Correspondence to Dr. M. Ricciardi Pingry Veterinary Hospital via Medaglie d'Oro 5 Bari 70126 Italy Phone: +39 080 553 3884 E-mail: [email protected]
dog appear similar to cervical ribs widely described in human medicine. In people, cervical ribs are associated with a high rate of stillbirth, early childhood cancer, and can cause the thoracic outlet syndrome, characterized by neurovascular compression at level of superior aperture of the chest. In dogs, only some sporadic anatomopathological descriptions of cervical ribs exist. In this report the radiographic and CT findings of these particular vertebral and rib anomalies along with their relationships with adjacent vasculature and musculature are shown intravitam in a dog. Specific radiographic and CT findings described in this report may help in reaching a presumptive diagnosis of this anomaly. Finally, their clinical and evolutionary significance are discussed. Vet Comp Orthop Traumatol 2015; 28: 145–150 http://dx.doi.org/10.3415/VCOT-14-07-0109 Received: July 23, 2014 Accepted: December 12, 2014 Epub ahead of print: February 4, 2015
Introduction A cervical rib is defined as a supernumerary rib, springing from one or both sides of one cervical vertebra usually the seventh, rarely the sixth, and very rarely the fifth (1). In the human population cervical ribs represent a rare, atavistic anomaly with an incidence of 0.2% to 1.0% (2, 3). They are twice as common in women as in men (68% versus 32%, respectively) and are bilateral in more than 50% of cases (4). To date descriptions of cervical ribs in dogs are limited to twelve reported necropsy findings, in which one or both transverse process of C7 resembled a rib.
Unfortunately, only a partial lateral radiograph and a single isolated vertebra in these anatomopathological specimens, are available for review (5, 6). In this report, we describe the presence of an anatomical anomaly involving the first ribs and the seventh cervical vertebra in a dog. The bone anomalies, resembling supernumerary cervical ribs, were found as incidental findings during the diagnostic work-up for a cervical spondylomyelopathy. The morphology of these bones and their relationships with the cervical spine and the adjacent musculature and vessels were assessed through the three-dimensional multislice computed tomography (CT).
Case description An 11-year-old, female Doberman Pinscher dog was evaluated for the complaint of a one month history of progressive inability to walk. Clinical and neurological examination findings included non-ambulatory tetraparesis, decreased postural reaction on all four limbs, severely decreased forelimb spinal reflexes, normal hindlimb spinal reflexes, and cervical discomfort. Neuroanatomic localization was the cervico-thoracic spinal cord (C6-T2 spinal cord segment – C4-T2 vertebral bodies). Haematology, serum chemistry analyses and urinalysis results were within normal limits. Orthogonal radiographic views of the cervico-thoracic and thoracic spine were obtained while the dog was under general anaesthesia. The lateral view radiographs demonstrated an abnormal triangular shape of the body of the C5-C6 vertebrae, narrowing of the C6-C7, and C7-T1 intervertebral disc spaces, and abnormal shape of the first ribs. The body of these bones appeared caudo-cranially flared and connected by a linear mineral opacity to the ventro-cranial aspect of the body of the seventh vertebra (C7) (▶ Figure 1 A). On ventrodorsal radiographic views, two welldefined rib-like opacities were visualized and were connected on both sides of the first ribs to the cranio-lateral aspect of C7. The left one showed a linear radiolucent area that separated it in two segments: one which was more cranial and connected to C7 (with perpendicular orientation to the axis of the spine), and a second directly connected to the body of the first rib (with parallel orientation to the axis of the spine) (▶ Figure 1 B). No anomalies in the shape and number of the remaining ribs were observed. Based on these findings, a presumptive diagnosis of cervical spondylomyelopathy with associated unknown
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Figure 1 A) Lateral and B) ventrodorsal radiographs of the cervico-thoracic spine. A) On the lateral view, the first ribs appear caudo-cranially flared and connected by a linear mineral opacity (arrow) to the ventro-cranial aspect of the body of the seventh vertebra. B) There are two well-defined rib-like opacities connecting on both sides the first ribs with the cranio-lateral aspect of the seventh vertebra (arrows). A radiolucent linear defect separates the left supernumerary rib in two segments (arrowhead). C5 = fifth cervical vertebra; C6 = sixth cervical vertebra.
Figure 2 Magnetic resonance imaging of the cervico-thoracic spine. A) Sagittal T2-weighted image; B) dorsal STIR; transverse T2-weighted image at C) C5-C6, D) C6-C7 and E) C7-T1 intervertebral disc spaces. There was severe C5-C6 and mild C6-C7 intervertebral disc protrusions with ventral spinal cord compression, dorsal C5-C6 spinal cord compression subsequent to hypertrophy of the ligamentum flavum and triangular shape of the C6 and C7 vertebral bodies. No signal changes of the cervicothoracic nerve roots were observed (C, D, E and arrows in B).
anomaly of the first ribs was made. In order to evaluate the spinal cord damage subsequent to the suspected cervical spondylomyelopathy and to clarify the anatomical relationships between the first ribs and the seventh vertebra, MRI and CT of the cervico-thoracic spine were performed after the radiographic examination. Magnetic resonance imaging was acquired under general anaesthesia using a 0.25 Tesla permanent magneta. The MRI sequences protocol included a fast spin echo T2-weighted acquired in sagittal and transverse planes, a short-tau inversion recovery (STIR) acquired in dorsal plane, and a spin echo T1-weighted acquired in sagittal and transverse planes before and after intravenous administration of paramagnetic contrast mediumb. Magnetic resonance imaging showed severe C5-C6 and mild C6-C7 intervertebral disc protrusions with ventral spinal cord compression, dorsal C5-C6 spinal cord compression subsequent to hypertrophy of the ligamentum flavum, and a triangular shape of the C6 and C7 vertebral bodies in the midsagittal plane. No signal changes of the cervico-thoracic nerve roots were observed (▶ Figure 2). Computed tomographic images were acquired using a 4-slice multi-detector CT scannerc, before and after the intravenous injection of iodinate contrast mediumd, with the patient positioned in sternal recumbency on the CT table under general anaesthesia. Computed tomography technical parameters were as follows: bone acquisition algorithm, 120 kVp, 200 mAs, 3.2 mm slice thickness, pitch of 0.8, and 0.75 s/rotation. Three-dimensional (3D) multiplanar reformatted and volume-rendered images were obtained using a dedicated 3D workstatione. Computed tomography images showed a flattened and highly flared profile of the first ribs. The proximal part of the ribs appeared Y-shaped, carrying a ESAOTE VET-MR GRANDE: Esaote, Genoa, Italy b Magnegita® – gadopentate dimeglumine 500 mmol/ ml – insight agents®; 0.15 mmol/kg BW: Agfa Healthcare Imaging Agents GmbH, Köln, Germany c Philips MX-8000: Philips Medical Systems, Cleveland OH, USA d Iopamigita®: Insight Agents GmbH®, Heidelberg, Germany e OsiriX DICOM-viewer: Pixmeo, Geneva, Switzerland
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M. Ricciardi et al.: Cervical ribs in a dog
short bone prominences that branched from the cranial margin of the rib and articulated with the transverse processes of C7. On the left side, the bone prominence articulated with C7 and was separated from the body of the first rib by an irregular line isoattenuating to soft tissue. A round region of interest (ROI) was traced within this gap to measure the Hounsfield Units (HU) mean attenuation value. A mean attenuation value of 87 HU was detected. No vascular anomalies nor abnormal anatomical relationships between the scalenus muscles, supernumerary ribs, and subclavian arteries and veins were observed. On the right side, the insertion of scalenus muscle was on the supernumerary rib (▶ Figure 3, ▶ Figure 4, ▶ Figure 5). Surgical decompression of the cervical spinal cord was performed by ventral slot at the C5-C6 intervertebral disc space followed by C5-C6 vertebral stabilization. After 15 days, the dog was re-evaluated and no significant improvement was noted. Based on its poor clinical condition the patient was euthanatized upon owner’s request. No further investigations were authorized by the owner.
Discussion The embryologic formation of cervical ribs seems to result from some failure in the conflict between forming brachial plexus and ribs. In higher vertebrates, the forming spinal nerves grow outwards at approximately right angles to the vertebral column to gain access to the developing limb buds and, as the column grows in length and the limbs descend, the nerves are forced to adopt an oblique course to reach the developing limbs. It is here that a conflict is said to arise between the passage of the nerves and the developing ribs. It is reported that when large nerve trunks press on comparatively small developing ribs, their growth is impeded and they remain stunted, forcing them ultimately to merge with the transverse process of the adjacent vertebra (7). In the thorax, where there is no conflict with a developing plexus, the ribs are free to grow in size and achieve independence from the column (1, 7–10). Animals that do not possess limbs, such as
Figure 3 Oblique multiplanar computed tomography reformatted images of the (A) left and (C) right first ribs. There is a flattened and highly flared profile of the first ribs (arrowheads). The proximal part appears Y-shaped, carrying short bone prominences (arrows) branching from the cranial margin of the rib and articulating with the transverse processes (tp) of C7. In the left rib, a non-calcified gap with cartilagineous mean attenuation values (rounded ROI–92 HU), resembling a pseudoarticulation, separates the cervical rib from the body of the first rib. B, D) Three-dimensional (3D) volume-rendered CT images of the cervico-thoracic spine (from C3 to T2), with complete removal of the scapulae. A 250 HU density threshold was used for the 3D display. Images illustrate (B) left lateral and (D) right lateral views. r2 = second rib.
snakes, retain paired ribs associated with virtually every vertebra with corresponding separate segmental nerves (8). The extent of growth of a cervical rib is determined by the nature of the obstruction on its path, which most frequently is nervous in origin (1, 7). However, this theory does not completely explain the embryologic formation of cervical ribs because it would be expected that the ribs should be associated with the upper cervical vertebrae (where there are no requirements for limb related nerves). To date, no reports exist describing a cervical rib associated with the upper four cervical vertebrae (7). In human medicine, there are four types of cervical ribs: 1) large, hypertrophic transverse process of C7; 2) rudimentary rib, but with free extremity and no connection to the first rib; 3) incomplete rib connected to the first thoracic rib by a fibrous band; 4) complete cervical rib fusing with
the first rib or connecting with it by a cartilaginous pseudoarticulation (11). In our patient, both the cervical ribs were attributable to the fourth type. The left cervical rib joined the first rib by a non-calcified gap that was suggestive of cartilaginous tissue based on its HU value. This arrangement appeared as a cartilaginous pseudoarticulation. The right cervical rib was completely fused with the first rib. The majority of people with cervical ribs are asymptomatic, but the presence of cervical ribs assumes clinical relevance in those people when these supernumerary bones compress one or more of the neurovascular structures traversing the superior aperture of the chest between the first rib and the scalenus muscles (costo-scalene triangle) (2). This condition is known as thoracic outlet syndrome (12, 13). Thoracic outlet syndrome is more commonly observed in women, and the onset of symp-
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A
B
C
D
Figure 4 Schematic representation of the costo-scalene triangle (asterisk) in normal (A) and cervical rib (B) patients as reported in human medical literature (14). When present, the supernumerary rib (cr) can narrow the costo-scalene triangle and compress the neurovascular bundle that passes between the middle and ventral (anterior) scalenus muscles. Schematic representation of the anatomical relationships between the neurovascular bundle, the first rib, and the scalenus muscles in a normal dog (C) and in our patient with the cervical rib (D). There is not a space comparable to the costo-scalene triangle between the middle and ventral scalene muscles and the neurovascular bundle passes ventrally to the ventral scalene muscle (15–18). In our dog, on the right side, the scalenus muscle was inserted directly on the cervical rib and, on both sides, there is no evidence of neurovascular compression. R1 = first rib; sm = middle scalene muscle; sv = ventral scalene muscle; a = subclavian artery; v = subclavian vein; p = brachial plexus; cr = cervical rib. Scheme A and B adapted from Brewin J, Hill M, Ellis H. The prevalence of cervical ribs in a London population. Clin Anat 2009; 22: 331–336. Scheme C and D original drawing.
toms usually occurs between 20 and 50 years of age (14). Approximately 10% of people with cervical ribs develop symptoms of thoracic outlet syndrome, secondary to the compression of the brachial plexus, also called neurogenic thoracic outlet syndrome (more than 90% of the cases), or due to compression of the subclavian vessels (either artery or vein), also called vascular thoracic outlet syndrome (less than 5% of cases). In some cases the neurological and vascular components may coexist (13–15).
The symptoms of nerve compression most frequently observed in neurogenic thoracic outlet syndrome are pain, paraesthesia, and weakness (12). Furthermore, compression of sympathetic neurons can cause vasomotor disturbances (16). In vascular thoracic outlet syndrome, compression of the subclavian artery can cause intermittent limb ischaemia, poststenotic dilatation of the artery or aneurysm formation. If the subclavian vein is compressed, venous insufficiency or even sub-
clavian vein thrombosis are observed (15, 16). In our patient, we were unable to investigate signs of possible brachial plexus compression secondary to the presence of the cervical ribs because of the concomitant non-ambulatory tetraparesis induced by the cervical spondylomyelopathy. However, no signal nor volume changes of brachial plexus nerve roots were evident on MRI. Furthermore, no clinical signs related to vascular compromise (neither arterial or venous) were observed on the forelimbs. Computed tomography angiography did not show compression of the subclavian arteries and veins. In humans, the scalenus muscles play an important role in the neurovascular compression when a supernumerary rib is present. Since the brachial plexus and the subclavian artery pass over the first rib just between the ventral (anterior) and middle components of the scalenus muscles (costo-scalene triangle), the neurovascular bundle can be compressed or trapped if this triangular space is narrowed by the presence of a cervical rib (4, 12–15). In domestic mammals, the subclavian artery and vein, and the brachial plexus pass ventrally to the ventral scalenus muscle, which is not separated from the middle component so as to create a space comparable to the costo-scalene triangle (15, 17–20) (▶ Figure 4). In our patient, CT did not show close anatomical relationships between scalene muscles, cervical ribs and subclavian arteries and veins. These vessels run on both sides much more ventrally to the muscles and to the supernumerary ribs (▶ Figure 5). Thus, this possible difference between humans and dogs in the level to which the subclavian vessels emerge from the chest and cross the scalene muscles, may influence differently the development of clinical signs in these two species, where cervical ribs are present. However the evaluation of further cases of cervical ribs in dogs is needed in order to verify this hypothesis. Cervical ribs may also have evolutionary significance in mammals. Among vertebrates, mammals have the lowest variability in the number and pattern of cervical vertebrae in comparison with other classes such as birds and reptiles (cervical ribs are normal in crocodiles) (1, 7). The only ex-
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M. Ricciardi et al.: Cervical ribs in a dog
ception is found in cervical rib cases in which the supernumerary ribs represent a partial or whole transformation of the seventh cervical vertebra into the first thoracic vertebra, thus, reducing the number of cervical vertebrae. In all vertebrate classes, the patterning of the axial skeleton is regulated by Hox genes and development of cervical ribs is a process that seems to be particularly susceptible to perturbations in Hox gene expression (21, 22). Interestingly, the most common abnormalities found in Hox gene-mutant mice are cervical ribs (23). At the same time, Hox genes have been shown to be involved in the proliferation of cell lines in mice and humans (24–26). Changes in Hox gene expression have been demonstrated for several types of tumours, including some childhood cancers, such as neuroblastoma, nephroblastoma and leukaemia, that were found to be associated with a high incidence of vertebral anomalies (24–27). A high incidence of cervical ribs was found in another study specifically devoted to find vertebral anomalies in 750 children with embryonal cancers (28). An incidence of around 25% of cervical ribs was found for the following embryonal and childhood cancers: neuroblastoma, brain tumour (astrocytoma and medulloblastoma), acute lymphoblastic and myeloid leukaemia, soft tissue sarcoma, nephroblastoma and endothelial myeloma (28). Furthermore, a strong association between cervical ribs and stillbirth has been described both in mice and humans (29–34). One study showed that at least 78% of the human foetuses with a cervical rib die before birth (35). Moreover data from autopsies performed on 225 stillborns (≥20 weeks) and 93 deceased live-born infants showed an overall higher prevalence of cervical ribs in stillborns than in liveborns who died in the first year (43.1% versus 11.8%) (34). Cervical ribs are due to disturbance of embryogenesis of the cervical axial skeleton, which in turns seems to be linked, as negative pleiotropic effect, to neoplastic proliferation of cell lines and a high rate of stillbirth and embryonal/childhood cancer. Consequently, these bone anomalies, for which inheritance has been suggested in dogs, are rare because most individuals
Figure 5 A) Transverse multiplanar computed tomography reformatted images at the level of the seventh cervical vertebra (C7). B) Oblique multiplanar computed tomography reformatted images of the right first rib at the level of the scalene muscles (sc). On both sides, the subclavian arteries and veins run ventrally to the cervical ribs (arrows) without anatomical relationships with the scalene muscles. On the right side, the insertion of scalene muscles was on the subernumerary rib (arrow in B). Rsa = right subclavian artery; lsa = left subclavian artery; rsv = right subclavian vein; lsv = left subclavian vein; R1 = first right rib; R2 = second right rib. The right subclavian vein is still not filled with contrast medium.
possessing them die before reaching a reproductive age (developmental constraint) (6, 23, 34). Based on these data it is possible to speculate that the incidence of cervical rib cases in dogs may be heavily underestimated due to a possible high rate of stillbirth.
Conclusion In conclusion, this report describes the radiographic and CT imaging findings of bilateral cervical ribs in a dog. The anatomy of these particular vertebral and rib anomalies along with their relationships with adjacent vasculature and musculature were especially well delineated on multiplanar and 3D volume-rendered CT imaging. In this case, the supernumerary bones were found as incidental findings; no vascular disturbances were evident and brachial plexus evaluation was not completely reliable clinically. However, further cases of cervical ribs in dogs need to be evaluated in order to establish the anatomical relationships between these supernumerary bones, the scalenus muscles, the first ribs, and their implication in neurovascular compression. In the absence of advanced knowledge on their clinical significance, the authors’ opinion is that the occurrence of cer-
vical ribs should be considered in the list of differential diagnosis in dogs presenting signs of nerve root or vascular compression affecting the forelimbs. Conflict of interest
None declared.
References 1. Adson AW, Coffey JR. Cervical rib; a method of anterior approach for relief of symptoms by division of the scalenus anticus. Ann Surg 1927; 85: 839–857. 2. Zou Chang K, Likes K, Davis K, et al. The significance of cervical ribs in thoracic outlet syndrome. J Vasc Surg 2013; 57: 771–775. 3. Gladstone RJ, Wakele CPG. Cervical ribs and rudimentary first thoracic ribs considered from the clinical and etiological standpoint. J Anat 1932; 66: 334–370. 4. Sanders RJ, Hammond SL. Management of cervical ribs and anomalous first ribs causing neurogenic thoracic outlet syndrome. J Vasc Surg 2002; 36: 51–56. 5. Morgan JP. Congenital anomalies of the vertebral column of the dog: A study of the incidence and significance based on a radiographic and morphologic study. Vet Radiol Ultrasound 1968; 9: 21–29. 6. Breit S, Kunzel W. Osteologische Besonderheiten an Wirbelsaulen von Rassehunden: eine röntgenologische und morphologische Studie [Osteological peculiarities of the vertebrae from pedigree dogs: a radiological and morphological study]. Wiener Tierarztliche Monatsschrift 1998; 85: 340–350.
© Schattauer 2015
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149
150
M. Ricciardi et al.: Cervical ribs in a dog 7. Black S, Scheuer L. The ontogenetic development of the cervical rib. Int J Osteoarchaeol 1997; 7: 2–10. 8. Davis DB, King JC. Cervical rib in early life. Am J Dis Child 1938; 56: 744–755. 9. Larsen WJ. Human Embryology. Edinburgh: Churchill Livingstone 2001; 84–104. 10. White JC, Poppel MH, Adams R. Congenital malformations of the first rib. Surg Gynaecol Obstet 1945; 81: 643–659. 11. Gruber W. Ueber die Halsrippen des Menschen mit vergleichend-anatomischen Bemerkungen [About the cervical ribs of man with comparative observations]. St. Petersburg: Commissionnaires de l'Académie Impériale des Sciences; 1869. pg. 614. 12. Urschel HC, Razzuk MA. Neurovascular compression in the thoracic outlet: changing management over 50 years. Ann Surg 1998; 228: 609–617. 13. Arthur LG, Teich S, Hogan M, et al. Pediatric thoracic outlet syndrome: a disorder with serious vascular complications. J Pediatr Surg 2008; 43: 1089–1094. 14. Köknel Talu G. Thoracic outlet syndrome. Agri 2005; 17: 5–9. 15. Brewin J, Hill M, Ellis H. The prevalence of cervical ribs in a London population. Clin Anat 2009; 22: 331–336. 16. Atasoy E. Thoracic outlet compression syndrome. Orthop Clin North Am 1996; 27: 265–303 17. Evans E, de Lahunta A. Miller's Anatomy of the Dog. 4th ed. Philadelphia, PA: Elsevier; 2013. pg. 213, 459-461, 507, 544, 620. 18. Barone R. Anatomia comparata dei mammiferi domestici. Vol. 2: Parte seconda – Miologia [Comparative anatomy of domestic mammals. Vol. 2:
19.
20.
21. 22.
23.
24.
25.
26.
Part II - Myology]. 3rd ed. Bologna: Edagricole, 2003. pg. 541, 551. Barone R. Anatomia comparata dei mammiferi domestici. Vol. 5: Angiologia. Parte prima: cuore e arterie [Comparative anatomy of domestic mammals. Vol. 5: Angiology. Part I: Heart and arteries]. 3rd ed. Bologna: Edagricole, 2003. pg. 217. Barone R. Anatomia comparata dei mammiferi domestici. Vol. 5: Angiologia. Parte seconda: vene e sistema linfatico [Comparative anatomy of domestic mammals. Vol. 5: Angiology. Part II: Veins and lymphatic system]. 3rd ed. Bologna: Edagricole, 2003. pg. 153-158. Krumlauf R. Hox genes in vertebrate development. Cell 1994; 78: 191–201. Horan GSB, Nagy Kovacs E, Behringer RR, et al. Mutations in paralogous Hox genes result in overlapping homeotic transformations of the axial skeleton: evidence for unique and redundant function. Dev Biol 1995; 169: 359–372. Galis F. Why do almost all mammals have seven cervical vertebrae? Developmental constraints, Hox genes, and cancer. J Exp Zool 1999; 285: 19–26. Corte G, Airoldi I, Briata P, et al. The homeotic gene products in the control of cell differentiation and proliferation. Cancer Detect Prev 1993; 17: 261–266. Lawrence HJ, Sauvageau G, Humphries RK, et al.The role of Hox homeobox genes in normal and leukemic hematopoiesis. Stem Cells 1996; 14: 281–291. Anbazhagan R, Raman V. Homeobox genes: molecular link between congenital anomalies and cancer. Eur J Cancer 1997; 33: 635–637.
27. Manohar CF, Salwen HR, Furtado MR, et al. Upregulation of Hoxc6, Hoxd1, and Hoxd8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation. Tumor Biol 1996; 14: 34–47. 28. Schumacher R, Mai A, Gutjahr P. Association of rib anomalies and malignancy in childhood. Eur J Pediatr 1992; 151: 432–434. 29. Jeannotte L, Lemieux M, Charron J, et al. Specification of the axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes Dev 1993; 7: 2085–2096. 30. Peters H. Varietäten der Wirbelsäule menschlicher Embryonen [Varieties of the spine of human embryos]. Gegenbaurs Morph Jahrbuch 1927; 58: 440–477. 31. Noback CR, Robertson GG. Sequences of appearance of ossification centers in the human skeleton during the first five prenatal months. Am J Anat 1951; 89: 1–28. 32. Meyer DB. The appearance of cervical ribs during early human fetal development. Anat Rec 1978; 190–481. 33. Bots J, Wijnaendts LC, Delen S, et al. Analysis of cervical ribs in a series of human fetuses. J Anat 2011; 219: 403–409. 34. Furtado LV, Thaker HM, Erickson LK, et al. Cervical ribs are more prevalent in stillborn fetuses than in live-born infants and are strongly associated with fetal aneuploidy. Pediatr Dev Pathol 2011; 14: 431–437. 35. Galis F, Van Dooren TJM, Feuth JD, et al. Extreme selection in humans against homeotic transformations of cervical vertebrae. Evolution 2006; 60: 2643–2654.
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