Introduction

VACTERL association summarizes multiple malformations not obviously associated with each other. The acronym refers to a rare, nonrandom co-occurrence of vertebral defects (V), anorectal malformations (A), cardiac defects (C), trachea-esophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L).¹ In children with existing congenital spinal deformity, additional associated anomalies occur with an incidence of 30–60%, and most of them are part of the VACTERL association.²

Congenital spinal malformations are common in animals, and concurrent congenital anomalies affecting other systems or other regions of the central nervous system are also mentioned, yet specifics are missing.³ In domestic animals, only one case report has been published of VACTERL association in a 50 day old female mixed-breed domestic cat with five of seven VACTERL association components.⁴ The abnormalities observed were supernumerary vertebra, supernumerary pair of ribs, caudal wedge vertebra, caudal hemivertebra, anal atresia, persistent cloaca, subvalvar pulmonic stenosis, large patent ductus arteriosus, hypoplastic right kidney, bilateral radial agenesis, and bilateral agenesis of the first digit. Carvallo et al. described a 3 yr old female mixed-breed dog with bilateral ectrodactyly and multiple wedge shape vertebrae, which are two components of VACTERL association.⁵ Malformation of the spinal cord was not part of the reported abnormalities.

Tethered spinal cord is a clinical syndrome classified as a subcategory of occult spinal dysraphism in which several forms of spinal dysraphism may be present.⁶ The term “dysraphism” arises from the Greek language and refers to a closure defect of the neural tube during embryologic development.⁶ These developmental intraspinal anomalies include thickened filum terminale, filum terminale lipoma, dermal sinus, lipomyelomeningocele, and split cord malformations.⁷ Dermoid sinus is one of the multiple congenital spinal malformations previously reported in a variety of dog breeds (English springer spaniel, rottweiler, Yorkshire terrier, golden retriever, Boerboel, Siberian husky, shih tzu, boxer, chow chow, Great Pyrenees, and bulldog) and cats.^8,9 It is a congenital defect in which the skin fails to separate completely from the ectodermal neural tube during the embryonic growth.^8,9,10,11 There are six types based on the degree of penetration in the subcutaneous tissues (I, II, III, IV, V, and VI) and three types based on the location dorsal midline in relation with the spine (a), on the head (b), and nasal dermoid sinus (c).⁸ A genetic component with a prevalence of 5.3% has been identified in the Rhodesian ridgeback and its mixes.¹¹ To date, five golden retrievers have been reported with dermoid sinus, with three localized to the nose, one to the head, and one dermoid sinus type II localized to the spine at the level of C7, and none of these had reported spinal cord involvement.^10,12,13

This is the first report of a dermoid sinus type IV in a golden retriever and, moreover, the first report of spinal cord malformation occurring concurrently with spina bifida and limb malformation resembling VACTERL association in people.

Case Report

A 2 mo old male intact golden retriever presented for evaluation of a small circular indentation of the skin and congenital malformation of the left thoracic limb. Physical examination revealed a malformation of the left thoracic limb distal to the carpus, characterized by absence of the digits III and IV, causing a nonweight-bearing lameness. At the level of the cranial thoracic spine, a small circular indentation of the skin was seen in-between the scapulae, with a palpable tract under the skin (Figure 1A). Complete neurological examination was normal.

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Radiographs of the left thoracic limb showed metacarpal and digital aplasia of digits III and IV, and several carpal bones were aplastic, hypoplastic, and malformed. These findings were consistent with a congenital ectrodactyly malformation (Figure 1B). Radiographs of the thoracic spine showed splitting of the dorsal spinous processes of T4 and T5 vertebrae on the ventro-dorsal view, consistent with spina bifida. No abnormalities were detected on lateral thoracic views or in the cervical spine. Magnetic resonance imaging of the thoracolumbar spine was performed using a 1.5 tesla MRI unit¹. Sagittal and transverse T2-weighted, T1-weighted, and T1-weighted postcontrast (gadopentetate dimeglumine², 94 mg/kg) sequences were acquired. Images revealed an invagination of the epidermal and dermal tissues towards the spinous process of T4 and T5 vertebrae. A tract was visible connecting the spinal cord with the skin layers. The normal morphology of T4 and T5 was lost, lacking the normal vertebral arch and splitting of the dorsal spinous processes between which the tract lay. The tract was filled with cerebrospinal fluid (hyperintense on T2 and hypointense on T1-weighted images) up to the level of the dorsal aspect of the T4 and T5 spinous processes. The spinal cord was deviated dorsally from T1 to T8 vertebrae, with its maximum deviation at the level of T4 and T5 vertebrae. At this level, the spinal cord was located between the T4 and T5 spina bifida at its ventral aspect (Figure 2A, B). Imaging diagnoses included a dermoid sinus type IV or a meningocele.

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Surgical excision of the tract was elected to prevent potential future complications. A midline skin incision from T1–T8 spinous process was performed, the indentation was excised, and care was taken not to damage the tract. The tract was followed ventrally by blunt dissection. A dorsal laminectomy was performed, removing the left dorsal spinous process of the spina bifida at T4 and T5 vertebrae. A durotomy just dorsal to the spinal cord was performed following full exposure of the tract, and the complete tract was removed. The position of the spinal cord remained elevated. A fat patch was placed onto the spinal cord, followed by routine closure. The dog recovered well from surgery, showing no neurological deterioration. Histopathological examination showed invagination of the epidermis forming a tract that was lined by stratified squamous epithelium and some hair follicles growing perpendicular to the sinus tract. Immunostaining revealed cells positive for cytokeratine, confirming the presence of epithelial lining reaching from the skin into the tract. Based on these findings, a diagnosis of dermoid sinus type IV was made.

Further investigations including abdominal ultrasound and echocardiography were recommended following diagnosis of dermoid sinus type IV and literature review. The aim was to investigate the occurrence of other, possibly silent, malformations, as reported in people with VACTERL association. Unfortunately, the owner declined further investigations due to financial restrictions and the lack of clinical signs. Nevertheless, the owner elected amputation of the malformed limb 3 wk later because of recurrent skin trauma and persistent infection. The dog recovered well and at the time of re-examination 2 mo later, the dog showed no neurological deficits and a normal physical examination.

Discussion

Reports and specifics about multiple concurrent congenital malformations occurring in animals are rare. In people, VACTERL association summarizes multiple malformations not obviously associated with each other referring to vertebral defects (V), anorectal malformations (A), cardiac defects (C), trachea-esophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L).¹ The condition was termed association because these malformations were observed to occur more often together than it would be expected by chance and because no evidence for a single, unifying cause that would result in the condition being termed syndrome was found.¹⁴ Development of a unifying embryopathogenesis that encompasses the major malformations of the VACTERL association faces significant challenges. The malformations affect five different anatomical systems, of which some make their appearance early in the embryological period, 23–30 days post conception, whereas others occur later in the embryogenesis.¹⁵ Potential explanations for this association of congenital malformations include chronic teratogenic influences throughout the period of embryogenesis, an inaugural malformation that secondarily disturbs development of other anatomical structures, the so-called malformation sequence or cascade, disturbances of molecular pathways or mutations of single genes that are critical in the formation of the multiple anatomic systems affected, and disturbances in the developmental process that is essential to all systems affected.¹⁵ Some studies have attempted to determine how many abnormalities must be present to fall into the group of VACTERL association. In initial reports, it was found that around 80% of cases diagnosed with VACTERL association had only two congenital defects.¹⁶ More recently, other authors considered that the presence of at least three defects was necessary for a VACTERL association diagnosis.⁴ Only two cases resembling VACTERL association are reported in veterinary literature: a 50 day old female mixed-breed domestic cat with vertebral abnormalities, anal atresia, radial agenesis, and cardiovascular and renal deficits; and a 3 yr old female mixed-breed dog with limb and spinal malformation.^4,5 Following the initial reports about VACTERL association in people, the dog would fall into the group of malformations qualifying for VACTERL association. The here-reported dog was a 2 mo old male intact golden retriever with two congenital malformations, one affecting the vertebrae and one affecting the limb, and, thus, similarly resembled VACTERL association in people. The presented dog had a third malformation affecting the spinal cord, a dermoid sinus type IV, which has not been reported in a golden retriever previously. Dermoid sinus or spinal cord malformations are currently not reported as part of the malformations listed under VACTERL association. Yet, interestingly, in people, 39% of children with VACTERL association required surgery for tethered spinal cord.⁷ Moreover, a strong association of tethered cord with certain VACTERL features was found. Those with a tethered spinal cord were more likely to have vertebral and renal malformations and less likely to have cardiac anomalies or tracheoesophageal fistula.⁷ Because neither of these associations excluded the possibility of spinal cord tethering, a complete screening for these abnormalities is recommended in children with VACTERL association.⁷

The incidence of VACTERL association estimated in human medicine is between 1/10,000 and 1/40,000 infants.¹⁴ In people, genetic and environmental factors are suggested in the etiology of the disorder.¹ Certain VACTERL malformations, particularly vertebral, cardiac, and limb malformations, have been found in infants of mothers with diabetes mellitus. The mechanism by which maternal diabetes predisposes to malformations appears complex.¹⁵ Some human studies have suggested that the incidence is higher in males. Because the causes of VACTERL association appear to be heterogeneous, explanations of male overrepresentation may include X-linked inheritance in some instances, sex-influenced expression, and mechanism related to imprinting defects.¹⁴ The etiology of a proposed VACTERL association in dogs remains unknown. Neither genetic nor environmental factors affecting pregnancy can be excluded in our dog because of the lack of information of the dog’s background. Moreover, the limited number of published case reports does not allow drawing conclusions on the incidence of the gender in animals.

Prognosis is an important factor for owners when faced with a pet having one or multiple malformations. Looking into the human literature, survival of children with VACTERL association has improved overall, and children survive to adulthood more frequently than do children diagnosed decades ago because of increased availability and quality of surgical treatments, enhanced ventilator support, neonatal anesthesia, and intensive care management.¹⁷ Interestingly, approximately 25% of medically significant malformations that are component features of VACTERL association were not identified until after childhood, and include 40% of the vertebra, 50% of the cardiac, and 50% of the renal anomalies.¹⁷ This possibility is important to consider when a prognosis is given for pets affected by malformation seen with VACTERL association, especially if funds for further investigations are limited. No further investigations, such as cardiac or abdominal ultrasound, were performed in the presented dog due to the lack of associated clinical signs and financial restrictions. Therefore, we cannot exclude the possibility that clinically insignificant abnormalities may have been missed and may become relevant later in life. Both factors are important to communicate to owners when discussing the prognosis of their pet affected by obvious congenital abnormalities such as a limb malformation.

Dermoid sinus on its own is a well-known malformation in dogs.^8–13,18 Dermoid sinus type IV is attached to the spinal cord and can be confused with another spinal cord malformation, a meningocele. Both can have a similar clinical manifestation, and neural structures may become infected or inflamed, causing spinal pain and myelopathy.³ Advanced imaging cannot differentiate between a dermoid sinus type IV and a meningocele. Histopathological examination is required for diagnosis based on the presence or absence of epithelial tissue found in the tract, and its presence allowed a diagnosis of dermoid sinus type IV in the presented dog. Embryologically, dermoid sinus is a disorder of notochordal integration at the time of gastrulation.⁶ Malformations originating in this vital period of notochordal development show commonly complex spinal dysraphism, in which not only the spinal cord but also other organs deriving from or induced by the notochord are severely abnormal. Moreover, disorders occurring during gastrulation may potentially affect other germ layers as well.² Vertebrae, dermis of skin, striated skeletal muscle, connective tissue, and muscle of the head, and also urogenital, pulmonary, and cardiac system are mesenchymal in origin and many of these tissues are affected in VACTERL association.² It is possible that the incidence of spinal and spinal cord malformation with concurrent congenital malformations (VACTERL association) could be higher than reported; therefore, affected dogs should be strictly examined to identify all relevant abnormalities (silent or not) to provide a complete and accurate diagnostic evaluation and therapeutic plan for a patient.

Conclusion

To the authors’ knowledge, this report is the first case of dermoid sinus type IV reported in the golden retriever. Moreover, it is the first report in a dog describing a spinal cord malformation occurring concurrently with malformations resembling VACTERL association such as spina bifida and limb malformation. It highlights the importance for thorough investigations for less obvious malformations in dogs presented with a malformation to enable an appropriate prognosis for the owner.