Pierre Robin Sequence: A Familial, Clinical, and Pathoanatomical Record of an Affected Dachshund
This study describes a spontaneous case of Pierre Robin sequence in a nonhuman animal species. A miniature dachshund with micrognathia developed glossoptosis, respiratory distress, dysphagia, temporomandibular ankylosis, and a misaligned upper jaw. The severity of this condition resulted in death by obstructive apnea at the age of 8 mo. Dogs with Pierre Robin sequence can provide further knowledge and a greater understanding of this abnormality, leading to better management of affected individuals and improvement of therapeutic methods.
Introduction
Robin sequence or Pierre Robin sequence (PRS) is a clinical entity that manifests through a set of anatomical and clinical abnormalities resulting from micrognathia.1 The true micrognathia results from a severe degree of congenital mandibular hypoplasia enough to interfere with infant feeding.2 Cases of mandibular hypoplasia that don't reach this degree are termed brachygnathia in this report. An abnormally small mandible triggers a chain of events, characterized by the posterior displacement of the tongue (glossoptosis), which, in turn, causes respiratory difficulties. It can also cause dysphagia and affect the closing of the palatine processes, creating a cleft palate.1 It is not necessary to find a cleft palate in order to diagnose PRS; however, there are widely differing criteria among specialists that treat patients with PRS.3–5 Other abnormalities also may occur, such as temporomandibular joint ankylosis, misaligned teeth, and abnormal maxillary development.2,6,7
PRS is etiologically heterogeneous, in addition to being pathogenically and phenotypically variable, with isolated forms and forms associated with other anomalies.8 PRS can also be a part of certain well-known genetic syndromes.9 Congenital mandibular hypoplasia may be caused by extrinsic mechanical forces, intrauterine constraints affecting the development otherwise normal tissue, or by primary intrinsic growth disturbances (i.e., malformations).10
The spontaneous occurrence of PRS has so far been known only in humans, with an incidence varying from 1:14, 000 to 1:8500 live births for the cases that include a cleft palate, depending on the report.11,12 However, if cases without cleft palate are considered, the incidence should be higher.3 The mortality rate for PRS is estimated to be 1.7–11.3%.7
The following report concerns the natural occurrence of PRS in a miniature dachshund. The purpose is to attract the attention of veterinarians to recognize new spontaneous cases in small animals.
Case Report
A 3 mo old male miniature dachshund was referred for the clinical evaluation of a congenital craniofacial defect. It was born by a normal vaginal delivery following an uneventful pregnancy with an abnormally short mandible. The dog's owner informed us that his dog snored while it slept and required help to feed itself because the prehension of food was extremely difficult for it. Further, he often choked when eating.
Physical examination revealed that the observable segment of the mandible was only approximately 30% of its normal length (i.e., a case of micrognathia) and the upper jaw was slightly deviated to the right and ventrally (Figure 1A). The deciduous dentition was complete and the mobility of the temporomandibular joint was apparently normal. The dog was highly active and showed no clinical signs of any other abnormality. During in-hospital observation, the dog had episodic respiratory difficulty while sleeping or moving as a result of the caudal displacement of the tongue (glossoptosis, Figure 1B). Mandibular distraction osteogenesis to correct the micrognathia was recommended. The owner declined surgery; however, he allowed us to routinely examine and monitor the development of the dog.
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6183
The family history revealed that the proband was the product of a union between father and daughter, both affected by brachygnathia (Figure 2A). From this consanguineous union, two female siblings with brachygnathia and a male sibling with micrognathia were also born (Figure 2B). The male sibling died shortly after being weaned because it had not received adequate care to meet its specific needs during feeding. All puppies were born at term after an uncomplicated pregnancy and without a maternal history of illness or exposure to teratogens.
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6183
As the proband grew, his clinical condition worsened. The deviation of the upper jaw became more evident (Figure 3A) and the episodes of respiratory difficulty became more frequent and severe, especially after its dentition change was completed. With permanent dentition, the mobility of the temporomandibular joint gradually decreased until it became totally immobile, keeping the mouth minimally open. With temporomandibular ankylosis, his swallowing capacity was reduced, and choking became more frequent during feeding. This reflected on the general condition of the puppy because he was thinner and smaller than normal for its age. Tongue mobility was reduced to the point that the tip became permanently exposed to the air and became chronically parched (Figure 3B). The tongue base was caudally displaced (glossoptosis), leading to respiratory distress that became more intense during sleep and when the dog was agitated. On two occasions, the dog was presented for emergency attention, presenting with an obstructive apnea. It was necessary to clear the puppy's blocked airways and supply it with O2 to revive it. Although the patient's condition was declining, the owner once again refused to authorize mandibular distraction osteogenesis. At 8 mo of age, the dog suffered another apneic crisis and died.
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6183
At the time of the postmortem examination, the cadaver had pharyngeal obstruction caused by the base of the tongue blocking the flow of air to the larynx, confirming death by asphyxia. Dissection of the head revealed bilateral osseous fusion of the tympanic bulla with the respective mandibular ramus at the level of the angular process, causing temporomandibular ankylosis (Figure 4A). In the joint interfaces, there was no osseous fusion, only fibrous adhesion. This also occurred on both sides of the cranium, between the mastoid process and a bone projection originating in the angular process. The mandible, without muscles and integument, measured 60% of the normal length and the shortened part was the mandibular body. The mandibular rami had a slightly reduced width and the coronoid process was more caudally curved (Figure 4B). The upper jaw was laterally deviated by 10° to the right and its rostral end was ventrally deviated by 20°, with a consequent bilateral reduction of the canine diastema. From a cranial view, there was mild anticlockwise rotation of the maxilla and clockwise rotation of the mandible in such a way that the maxilla and the mandible were closer in the right half than on the left. Furthermore, there was an alteration to the angles and proportions between the craniofacial parts (Figure 4C). All the permanent teeth were found but several of those located in the mandible were crooked. There were no abnormalities in the other organs. Skull measurements were taken to enable comparison with future cases that may arise (Table 1).
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6183
Discussion
A shorter than normal mandible (mandibular hypoplasia) is frequently found by small animal clinicians in different canine breeds, a common condition referred to by breeders as “overshot.” This abnormality has rarely been reported in the scientific literature.13–15 A study by Phillips (1945) contains a brief commentary on a cocker spaniel puppy with a mandible measuring only approximately one-quarter of the normal length. No further details or images were provided.14 More severe cases of mandibular hypoplasia, in which mandibular size is markedly reduced (micrognathia), seem to be uncommon among dogs and have never been reported as the cause of glossoptosis associated with respiratory distress, obstructive apnea, and temporomandibular ankylosis (in currently indexed journals, that is). In three articles, the authors conclude that their data are compatible with monogenic autosomal recessive inheritance.13–15 The pedigree shown in Figure 2B is also compatible with that pattern of inheritance with variable expressivity, but it does not allow us to exclude autosomal inheritance with incomplete dominance. Those affected by micrognathia would be one of the homozygous types (A1A1), those affected by brachygnathia would be the heterozygotes (A1A2), and normal individuals would be the other homozygous type (A2A2). The fact that the two males were more severely affected is probably a random event because different degrees of congenital mandibular hypoplasia have been observed in dogs of both sexes.13–15
Newborn dogs have short jaws compared with adult dogs, which facilitates the sucking of milk. During the neonatal period, the proband managed to suckle, but with the subsequent uneven development of the maxilla and mandible, he had difficulty with food prehension.
The study authors hypothesized that the upper jaw was misaligned because growth took place without the stability that the mandible normally provides. The absence of a cleft palate in the proband may have been the result of the canine orolingual anatomy, which facilitates the forward projection of the tongue and thus reduces the pressure on the palatine processes, or it may have been merely a random phenomenon.
The temporomandibular ankylosis that occurred with replacement of deciduous teeth by permanent dentition in addition to the extremely severe malocclusion locked the mandible in a position that permitted osseous fusion with the tympanic bulla and fibrosis of the temporomandibular joint. Considering that other craniofacial abnormalities, such as premature suture fusion, cause a dysmorphic skull shape, the subsequent growth with fused craniomandibular structures must have been the cause of the altered proportions between the bones, leading to craniofacial dysmorphism (Figure 4B).16
The term glossoptosis must not be confused with rostroventral ptosis of the tongue, which is a common phenomenon when there are missing teeth or in the case of marked brachygnathia (Figure 2A).
The development of several anatomical and clinical abnormalities as a result of an initial abnormality corresponds, in dysmorphology, to the concept of sequence and, considering that in this case the initial abnormality was micrognathia, corresponds specifically to the concept of PRS.1,17 The absence of cleft palate among the abnormalities reported is also known in human cases, and many specialists assert that the presence of a cleft palate is not necessary for the diagnosis of PRS.1,3–5 Therefore, this case is a spontaneous occurrence of nonsyndromic PRS in a nonhuman animal species.
Conclusion
The detection of similar cases in small animals may be useful for the development of studies on the pathogenesis and the genetics of PRS and mandibular morphogenesis. This will ultimately lead to better management of affected individuals and improvement of therapeutic methods.
Photograph of the clinical phenotype of the proband at 3 mo of age. A: Micrognathia and deciduous teeth. B: Ventral deviation of the upper jaw. Note that in both photographs only a small end of the tongue appears, a sign of its caudal displacement (glossoptosis), contrary to what occurs when the mandible is just a little short and the tongue tends to be rostroventrally displaced.
A: Photograph of the mother of the proband presenting with brachygnathia and rostroventral ptosis of the tongue. B: Pedigree of the dogs described in the case report.
Photograph of the clinical phenotype of the proband at 8 mo of age. A: Lateral deviation of the upper jaw. B: Permanent dentition with no diastema between the incisors and upper canine teeth as well as a parched tongue due to constant exposure to the air (reduced mobility). Note that despite the exposure of the tip, the base of the tongue is caudally displaced (glossoptosis). Compare this photograph with the photograph of the mother's tongue with normal mobility and a normally positioned base (Figure 2A).
Necropsy findings. A: Right lateral deviation of the upper jaw bones and osseous fusion of the mandibular rami with the tympanic bullae (arrows). B: Micrognathia, severe malocclusion, crooked lower teeth, and altered craniofacial angles and proportions. C: Drawing of a normal dachshund cranium for comparison.
Contributor Notes
